Showing posts with label ALS-2200 (VX-135). Show all posts
Showing posts with label ALS-2200 (VX-135). Show all posts

Thursday, May 1, 2014

Vertex ends hepatitis C investment as sales fall

Vertex ends hepatitis C investment as sales fall
NEW YORK (AP) — Vertex Pharmaceuticals, which reported more than $1 billion in sales of its hepatitis C drug Incivek in 2012, said Thursday it won't invest any more money on research and development of new treatments for the disease.

Vertex said it will license an experimental hepatitis C drug called VX-135 to Alios BioPharma. Revenue from Incivek dropped almost 90 percent in the first quarter as the drug was supplanted by newer treatments and Vertex sold its overseas marketing rights.

In April Gilead Sciences Inc. said sales of its hepatitis C drug Sovaldi totaled $2.27 billion in its first full quarter on the market. Sovaldi got U.S. approval in December and European Union approval in January.

Vertex wrote down the entire value of one experimental treatment for hepatitis C during the fourth quarter and it took an impairment charge related to another. The company also cut about 370 jobs in response to competition from other hepatitis C treatments...

Tuesday, August 27, 2013

Vertex’s VX-135 partial hold signals heightened FDA scrutiny toward HCV drugs

Vertex’s VX-135 partial hold signals heightened FDA scrutiny toward HCV drugs

By Christine Livoti in New York

Vertex Pharmaceuticals’ (NASDAQ:VRTX) hepatitis C virus (HCV) drug VX-135 and the recent partial clinical hold placed on it signal heightened FDA scrutiny toward HCV drugs, experts said. 
Still, most experts expressed optimism the partial hold will be removed and that the 200mg dose will advance. 
Other therapies developed to treat HCV that are similar to VX-135, a direct-acting antiviral (DAA) have been shown to trigger only transient elevations in liver enzymes, which are less of a concern.... 
Mild ALT increases seem to be quite common with many DAAs, a second European expert added. Either the elevation associated with VX-135 must be higher or the frequency greater than what has been observed with other DAAs to merit the partial clinical hold, he speculated....

Continue Reading......
 
This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com

Thursday, July 25, 2013

VX-135 -Vertex Sees Liver Toxicity With Emerging Hep C Drug, Faces FDA Hold

UPDATE 1-U.S. FDA puts hold on Vertex hepatitis study

Bill Berkrot

July 25 (Reuters) - Vertex Pharmaceuticals Inc said U.S. health regulators placed a partial clinical hold on its mid-stage study of an experimental oral hepatitis C treatment because of potential liver problems, sending its shares sharply lower on Thursday.

Vertex said the U.S. Food and Drug Administration took the action on the Phase II study of its VX-135 in combination with the standard hepatitis drug ribavirin after elevated liver enzymes were observed in three patients taking the 400 milligram dose of its drug.

As a result of the hold, the U.S. biotechnology company said it was unable to evaluate results of the trial, even for those patients who had been getting the 200 mg dose of VX-135.

"We are committed to continuing to work closely with the FDA to provide the data needed to support evaluation of a 200 mg dose of VX-135 in the U.S.," Robert Kauffman, Vertex's chief medical officer, said in a statement.

The halted trial was being conducted in Europe. The 400 mg arm of the study was discontinued and the patients' liver enzymes returned to what they had been prior to entering the trial, Vertex said.

A U.S. study evaluating 100 mgs of VX-135 was not affected, the company said.

VX-135 is also being studied at 100 mg and 200 mg in combination with Bristol-Myers Squibb Co's daclatasvir, a highly promising hepatitis drug from a different class of oral medicines.

Vertex has the market leading hepatitis C treatment with Incivek. But that drug must be taken with the difficult to tolerate injected drug interferon to provide high cure rates.

Incivek sales have been declining sharply as patients wait for new all oral treatment regimens that promise very high cure rates without the need for interferon and the miserable flu-like symptoms that come with it.

The first of those are expected to become available in 2014 from other companies and Vertex has been playing catch-up.

"With our ongoing studies in the U.S., Europe and now New Zealand with VX-135 and daclatasvir, our strategy in hepatitis C is unchanged - to develop an all-oral therapy that provides a high cure rate across multiple hepatitis C genotypes," Kauffman said.

Vertex shares were down more than 9 percent at $80 in after hours trading after closing at $87.62 on Nasdaq.

Vertex Press Release

July 25, 2013

Vertex Provides Update on Ongoing All-Oral Studies of VX-135 in Hepatitis C

-U.S. Study: FDA places partial clinical hold on ongoing Phase 2 U.S. study of VX-135, preventing evaluation of 200 mg dose following observation of elevated liver enzymes in patients receiving 400 mg of VX-135 in combination with ribavirin in Phase 2 study in Europe; evaluation of 100 mg dose continues in U.S.-

-European Study: 12-week dosing complete in 100 mg and 200 mg VX-135 dose groups in combination with ribavirin in Phase 2 study; 70% and 80%, respectively, of patients achieved undetectable HCV RNA by week 4 and treatment was well tolerated with no discontinuations or serious adverse events reported through 12 weeks-

-New Zealand Study: dosing ongoing in Phase 2 study of 100 mg and 200 mg of VX-135 in combination with daclatasvir, an NS5A replication complex inhibitor-

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the company has received notice from the U.S. Food and Drug Administration (FDA) that a partial clinical hold has been placed on Vertex's ongoing Phase 2 U.S. study of the nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135. The partial clinical hold prevents evaluation of a 200 mg dose of VX-135 in the U.S. study following observation of reversible elevated liver enzymes in patients receiving 400 mg of VX-135 in combination with ribavirin in a Phase 2 study in Europe. Evaluation of a 100 mg dose of VX-135 in combination with ribavirin as part of the 12-week Phase 2 study in the U.S. is continuing as planned.

Vertex recently completed dosing of 100 mg and 200 mg of VX-135 in combination with ribavirin as part of the 12-week Phase 2 study in Europe, and both doses were well tolerated with no discontinuations. No serious adverse events have been reported and no liver or cardiac safety issues have been identified. Vertex also recently initiated dosing of 100 and 200 mg of VX-135 in combination with daclatasvir as part of a Phase 2 study in New Zealand.

"Developing safe and effective medicines for patients is our goal," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "We are committed to continuing to work closely with the FDA to provide the data needed to support evaluation of a 200 mg dose of VX-135 in the U.S."

Ongoing Studies of VX-135

Multiple studies of VX-135 as part of all-oral treatment regimens are ongoing, including:
U.S. Study of VX-135 in Combination with Ribavirin: Dosing of 100 mg of VX-135 in combination with ribavirin as part of a 12-week Phase 2 study in the United States is ongoing, and evaluation of this dose group is continuing as planned. Ten patients with genotype 1 hepatitis C are enrolled in this dose group, and all patients have now completed at least 10 weeks of treatment. Complete safety and efficacy results from the 100 mg arm of the study are expected to be available in the second half of 2013. Under the partial clinical hold, Vertex plans to complete evaluation of the 100 mg dose of VX-135 but will not evaluate a 200 mg dose of VX-135 in the United States without authorization from the FDA. At the request of the FDA, Vertex expects to complete submission of additional clinical, preclinical and pharmacokinetic data from ongoing VX-135 studies in the fourth quarter.
European Study of VX-135 in Combination with Ribavirin: Dosing of 100 mg and 200 mg of VX-135 in combination with ribavirin as part of a 12-week Phase 2 study in Europe is complete, and all patients are in the post-treatment follow-up period. Ten patients with genotype 1 hepatitis C were enrolled in each dose group and all 20 patients completed 12 weeks of treatment. Both the 100 mg and 200 mg doses were well tolerated, no serious adverse events have been reported and no liver or cardiac safety issues have been identified. All patients achieved undetectable HCV RNA during the 12-week dosing period, and 70 percent and 80 percent of patients in the 100 mg and 200 mg dosing arms, respectively, had undetectable HCV RNA within four weeks of initiating treatment. HCV RNA was undetectable at the end of the treatment period in all patients with available data. Complete safety and efficacy results from the 100 and 200 mg arms of the study are expected to be available in the second half of 2013. Following completion of enrollment in the 100 mg and 200 mg arms of the European study, the study was amended to evaluate a 400 mg dose of VX-135 in combination with ribavirin in ten patients. Elevated liver enzymes were observed in three of ten patients in this dose group, including one serious adverse event, and the 400 mg arm of the study was discontinued. Following the discontinuation of dosing, liver enzyme levels returned to baseline in all three patients.
Study of 100 and 200 mg Doses of VX-135 in Combination with Daclatasvir: Vertex and Bristol Myers Squibb Company (BMS) recently initiated dosing in New Zealand in a Phase 2 study of VX-135 in combination with daclatasvir, an NS5A replication complex inhibitor being developed by BMS. This first part of the study is evaluating 100 mg and 200 mg doses of VX-135 in combination with daclatasvir as part of 12-week treatment regimens in approximately 20 people with genotype 1 hepatitis C. Pending data from the initial cohort of patients, Vertex and BMS plan to expand the study to enroll additional patients with both genotypes 1 and 3. Safety and efficacy results from the first part of the study are expected to be available in early 2014.

VX-135 in Combination with Simeprevir: A drug-drug interaction study of VX-135 in combination with simeprevir in healthy volunteers is complete. A combination study of VX-135 and simeprevir is planned for the second half of 2013 in patients with genotype 1 hepatitis C, pending availability of additional data. Simeprevir (TMC435) is a once-daily investigational hepatitis C protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB.
Termination of Collaboration with GlaxoSmithKline (GSK): In June, Vertex and GSK mutually decided to cease the collaboration for a Phase 2 study of VX-135 and GSK-2336805 and prioritize other projects. The preclinical and early-stage clinical data support continued development of VX-135 and of GSK-2336805.

About VX-135

VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Vertex gained worldwide rights to ALS-2200, known as VX-135 in Phase 2 studies, through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the third paragraph of the press release and statements regarding (i) Vertex's expectation that it will complete submission of additional clinical, preclinical and pharmacokinetic data in the fourth quarter of 2013; (ii) the plan to complete the evaluation of the 100 mg dose of VX-135 in the United States; (iii) the timing of availability of data from the U.S. and European studies of VX-135 in combination with ribavirin and from the first part of the study of VX-135 in combination with daclatasvir; (iv) the plan to expand the study of VX-135 and daclatasvir to enroll additional patients with both genotypes 1 and 3 HCV infection; and (v) the planned combination study of VX-135 and simeprevir. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the partial clinical hold prevents evaluation of the 200 mg dose of VX-135 in the United States, that the clinical development program for VX-135 may be delayed by the partial clinical hold, that the FDA may not lift the partial clinical hold on VX-135 or allow the company to pursue further development of VX-135 in the United States, that the outcomes of Vertex's planned and ongoing clinical studies of VX-135 may not be favorable, that VX-135 may not be safe or efficacious and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

VRTX — GEN
Vertex Contacts:
Media: Zach Barber, 617-341-6470
mediainfo@vrtx.com
or Investors: Michael Partridge, 617-341-6108
or Kelly Lewis, 617-961-7530
Source: Vertex Pharmaceuticals Incorporated
News Provided by Acquire Media

Vertex Sees Liver Toxicity With Emerging Hep C Drug, Faces FDA Hold 
Luke Timmerman

Vertex Pharmaceuticals suffered a meaningful setback today in its bid to remain a long-term player in the treatment of hepatitis C.

The Cambridge, MA-based biotech company (NASDAQ: VRTX) said today that the FDA has stopped the company from giving certain doses of its VX-135 drug candidate for hepatitis C in a mid-stage U.S. study, after seeing evidence of liver toxicity in patients in Europe. The FDA put a hold on Vertex’ plans to deliver 200-milligram doses of VX-135 in the U.S., but has allowed the study to continue enrolling patients on a lower, 100 milligram dose.

That decision was made after researchers saw liver toxicity in three of 10 European patients who got 400 milligrams of the Vertex drug, before they stopped enrolling patients in that group. The liver toxicity, measured in an increase in liver enzymes, was reversible once patients quit taking the drug, Vertex said. Vertex said that patients on the 100 and 200-milligram doses were able to tolerate the drug well, and none of those dropped out of 12-week study in Europe because of side effects.

“Developing safe and effective medicines for patients is our goal,” said Robert Kauffman, Vertex’s chief medical officer, in a statement. “We are committed to continuing to work closely with the FDA to provide the data needed to support evaluation of a 200 mg dose of VX-135 in the U.S.”

Vertex shares fell 11 percent, to $78 a share, in after-hours trading following the announcement.

The clinical hold is just the latest setback for Vertex in hepatitis C. Although the company blazed a new trail in the field by winning FDA approval in 2011 with its protease inhibitor telaprevir (Incivek), that treatment still must be given in combination with injectable interferon alpha, which causes flu-like side effects. Competitors such as Gilead Sciences (NASDAQ: GILD) and AbbVie (NYSE: ABBV) are both ahead in late-stage development with all-oral combination regimens that have increased hepatitis C cure rates without subjecting people to interferon. The results with competing drugs have been so compelling the past couple years that many hepatitis C patients have elected to wait until the new compounds are approved by the FDA instead of taking the currently available compound from Vertex.

VX-135, a nucleotide polymerase inhibitor, represents one of Vertex’s best chances to remain competitive in a landscape dominated by all-oral therapy. Vertex got the rights to this molecule through a collaboration with South San Francisco-based Alios Biopharma in 2011.

Vertex outlined a list of studies that remain ongoing with VX-135 in today’s statement. The drug is still being tested in combinations with compounds from Bristol-Myers Squibb and Johnson & Johnson, although Vertex said today that a VX-135 collaboration with GlaxoSmithKline ended last month.

http://www.xconomy.com/boston/2013/07/25/vertex-sees-liver-toxicity-with-hep-c-drug-faces-fda-hold/

Tuesday, April 30, 2013

Vertex Reports First Quarter 2013 Financial Results and Reviews Recent Progress in Development Programs for Cystic Fibrosis and Hepatitis C

Vertex reported fourth successive quarterly loss on plunging sales of its hepatitis C drug, Incivek -Click here.. 

Vertex Reports First Quarter 2013 Financial Results and Reviews Recent Progress in Development Programs for Cystic Fibrosis and Hepatitis C

-First quarter 2013 total revenues of $328 million, including net product revenues of $206 million for INCIVEK in hepatitis C and $62 million for KALYDECO in cystic fibrosis-

-Cystic fibrosis: Enrollment ongoing in Phase 3 program for VX-809 in combination with ivacaftor for people with two copies of the F508del mutation-

-Hepatitis C: multiple all-oral combination studies ongoing with the nucleotide analogue HCV polymerase inhibitor VX-135-

Excerpt... Full press release here....

Hepatitis C

Vertex’s strategy in hepatitis C is to develop new all-oral treatment regimens of 12 weeks or less in duration with a goal of providing a high viral cure rate and improved tolerability.

Multiple Ongoing Studies of VX-135 as Part of All-Oral Treatment Regimens

Vertex is currently evaluating multiple all-oral regimens that include VX-135, Vertex’s nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor. Ongoing and planned studies include:

Genotype 1
Two Phase 2 studies of VX-135 in combination with ribavirin are currently ongoing in people with genotype 1 HCV infection. Vertex today announced that one of these studies is fully enrolled.

A drug-drug interaction study of VX-135 in combination with simeprevir is ongoing in healthy volunteers. Simeprevir (TMC435) is a once-daily investigational hepatitis C protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB.

Genotypes 1, 2 or 3 and People with Cirrhosis

Vertex plans to conduct two Phase 2 studies of VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir. An initial study in people with genotype 1 HCV infection is planned for the second quarter of 2013. Vertex plans to begin a subsequent study in people infected with genotype 1, 2 or 3 HCV, including those with cirrhosis, in the second half of 2013, pending data from the initial study.

Vertex expects to obtain the first data from all-oral studies of VX-135 in the second half of 2013, including data from the initial study of VX-135 with daclatasvir and from the studies of VX-135 with ribavirin.

Data for ALS-2200 (VX-135) in Genotypes 2, 3 and 4 and in People with Cirrhosis Presented at EASL

At the 48th Annual Meeting of the European Association for the Study of the Liver (EASL), Vertex announced new data from a 7-day viral kinetic study of ALS-2200 in people with genotypes 2, 3 and 4 HCV and those with cirrhosis. The data showed significant reductions in HCV RNA after seven days of dosing with ALS-2200 (200 mg) once daily and were consistent with previously reported data in people with genotype 1 chronic HCV infection. ALS-2200 was well-tolerated in this study, there were no serious adverse events and no patients discontinued due to adverse events. Additional details on these data were provided in a press release issued April 23, 2013.

Data from CONCISE Study of Telaprevir Presented at EASL

Also at EASL, Vertex announced new data from an interim analysis of the CONCISE study, which showed that treatment with telaprevir combination therapy for a total of 12 or 24 weeks resulted in high viral cure rates in people with genotype 1 HCV with the IL28B CC genotype who had a rapid viral response and completed at least 12 weeks of treatment. The safety profile of telaprevir combination therapy observed in the CONCISE study through the time of the interim analysis was similar to that seen in previously reported clinical trials. Additional details on these data were provided in a press release issued April 24, 2013.

Tuesday, April 23, 2013

EASL: Vertex announced new data from viral kinetic study of ALS-2200 (VX-135)


ALS-2200 (VX-135) Viral Kinetic Study Shows Significant Reduction in HCV RNA in People with Genotype 1 Hepatitis C Virus Infection and Cirrhosis, and in People with Genotypes 2, 3 or 4 HCV Infection

- After seven days of once-daily dosing with 200 mg of ALS-2200, genotype 1 patients with cirrhosis had a median 4.08 log10 reduction in HCV RNA; among people with genotypes 3 or 4, there was a median 4.65 log10 reduction in HCV RNA -

AMSTERDAM, Apr 23, 2013 (BUSINESS WIRE) -- --- Data are consistent with previously reported ALS-2200 results in people with genotype 1 HCV infection -

--- ALS-2200 was well-tolerated, with no discontinuations due to adverse events-

Vertex Pharmaceuticals Incorporated  today announced new data from a viral kinetic study of the uridine nucleotide analogue ALS-2200 (VX-135) in development for the treatment of hepatitis C.

There was a median 4.08 log10 reduction in hepatitis C virus (HCV) RNA after seven days of dosing with 200 mg once daily in treatment-naive people with genotype 1 chronic HCV infection and compensated cirrhosis. Among treatment-naive people with genotypes 3 or 4 chronic HCV infection, there was a median 4.65 log10 reduction in HCV RNA after seven days of dosing with 200 mg once daily. Prior to a protocol amendment, one treatment-naive person with genotype 2 HCV infection received 100 mg of ALS-2200 once daily for seven days, and had a 5.04 log10 reduction in HCV RNA after seven days of dosing. ALS-2200 was well-tolerated in this study, there were no serious adverse events and no patients discontinued due to adverse events. These new data are consistent with previously reported data in people with genotype 1 chronic HCV infection, and will be presented the 48th Annual Meeting of the European Association for the Study of the Liver (EASL) in Amsterdam, Netherlands, April 24 to 28, 2013 (poster #866).

These data support Vertex's recently announced non-exclusive agreement with Bristol-Myers Squibb Company to conduct Phase 2 studies of once-daily all-oral treatment regimens containing VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir for the treatment of hepatitis C. As part of the agreement, Vertex plans to conduct two Phase 2 studies of the combination, including an initial study in treatment-naive people with genotype 1 HCV infection planned for the second quarter of 2013. Vertex plans to begin a subsequent study in treatment-naive people infected with genotype 1, 2 or 3 HCV, including those with cirrhosis, in the second half of 2013, pending data from the initial study.

"The viral kinetic data announced to date show the potential for VX-135 to be the backbone of all-oral treatment regimens," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "The data suggest that VX-135 holds promise as a treatment option for people with genotypes 1 through 4 HCV infection, and for people with cirrhosis, who urgently need more effective and better tolerated treatments."

Results of seven-day viral kinetic evaluations of ALS-2200 in treatment-naive people with chronic HCV infection are included in the following table:



        
               Cohort           Median Baseline  Median Change From       HCV RNA Levels
                                    HCV RNA       Baseline After 7     Below the Lower Limit
                                 (Log10 IU/mL)    Days of Treatment     of Quantification*
                                     (Min,             (Log10                 (LLOQ)
                                     Max)              IU/mL)                    n
                                                     (Min, Max)                 (%)
        --------------------   ---------------   ------------------   ---------------------
               Placebo               6.30               0.05                   0 (0)
        Genotypes 1, 3 and 4     (5.70, 7.35)       (-0.47, 0.66)
               (n=10)
        --------------------
         200 mg monotherapy          6.18               -4.54                 4 (50)
             Genotype 1          (5.66, 6.72)      (-3.81, -5.08)
                (n=8)
        --------------------
         200 mg + ribavirin          6.21               -4.18                 5 (63)
             Genotype 1          (5.14, 7.41)      (-3.62, -5.20)
                (n=8)
        --------------------
         200 mg monotherapy          6.64               -4.65                 5 (63)
          Genotypes 3 and 4      (5.59, 6.93)      (-4.05, -5.30)
               (n=8)**
        --------------------
               Placebo               6.41               0.06                   0 (0)
             Genotype 1          (6.36, 6.47)       (0.03, 0.10)
              Cirrhotic
               (n = 2)
        --------------------
         200 mg monotherapy          6.53               -4.08                 1 (13)
             Genotype 1          (6.08, 7.22)      (-2.91, -4.87)
              Cirrhotic
               (n = 8)
        --------------------
        *Roche COBAS(R) Taqman(R) HCV Assay v2.0 (LLOQ =
        25 IU/mL)
        **Prior to a protocol amendment, one person with genotype 2 HCV
        infection received 100 mg of ALS-2200 once daily for seven days,
        and had a 5.04 log10 reduction in HCV RNA after seven
        days of dosing.
        --------------------------------------------------------------------------
        


About VX-135 (ALS-2200)

Vertex has multiple ongoing and planned studies of VX-135 as part of all-oral treatment regimens, including a study in combination with ribavirin and studies with other direct-acting antivirals. Vertex plans to begin pivotal development of VX-135 as part of all-oral treatment regimens in 2014, pending data from these studies. The first Phase 2 data for VX-135 as part of an all-oral regimen are expected in the second half of 2013.

VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. ALS-2200 has shown pangenotypic activity in vitro. Vertex gained worldwide rights to ALS-2200 through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that focuses on the discovery of additional nucleotide analogues that act on the hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.(1) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(1) Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(1)Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.(2) If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(3,4)

More than 170 million people worldwide are chronically infected with hepatitis C.(5) In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.(6,7) Hepatitis C is four times more prevalent in the United States compared to HIV.(7) The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting for 82 percent of people with the disease.(8)Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.(9,10) By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(11)

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Vertex's press releases are available at www.vrtx.com.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, the statements of Dr. Kauffman in the third paragraph of this press release, and statements regarding (i) the timing and structure of multiple Phase 2 studies exploring all-oral treatment regimens that include VX-135 in combination with ribavirin and/or other direct-acting antivirals, including daclatasvir; (ii) Vertex's plans to begin pivotal development of VX-135 as part of all-oral treatment regimens in 2014, pending data from this studies and (iii) the first Phase 2 data for VX-135 as part of an all-oral regimen being expected in the second half of 2013. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the Phase 2 studies of VX-135 may be delayed or prevented, outcomes from any future studies of VX-135 may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

References:

(1) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed March 29, 2013.

(2) Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

(3) Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

(4) Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

(5) Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

(6) Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.

(7) Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed March 29, 2013.

(8) Smith, BD, et al. Hepatitis C Virus Antibody Prevalence, Correlates and Predictors among Persons Born from 1945 through 1965, United States, 1999-2008. AASLD 2011 Annual Meeting.

(9) Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

(10) Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

(11)Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009. Available at: http://www.vrtx.com/assets/pdfs/MillimanReport.pdf Accessed March 29, 2013.

http://cts.businesswire.com/ct/CT?id=bwnews&sty=20130423005419r1&sid=cmtx4&distro=nx

SOURCE: Vertex Pharmaceuticals Incorporated

Friday, April 5, 2013

VX-135/daclatasvir: Vertex signs agreement with Bristol-Myers for all-oral midstage studies for hepatitis C treatments


Vertex Enters Agreement with Bristol-Myers Squibb for Phase 2 All-Oral Studies of VX-135 in Combination with Daclatasvir for the Treatment of Hepatitis C

-Two Phase 2 studies to evaluate once-daily combination of Vertex's investigational nucleotide analogue VX-135 and BMS' investigational NS5A replication complex inhibitor daclatasvir-

-Study in people with genotype 1 hepatitis C planned to begin in second quarter of 2013-

-Study in people with genotypes 1, 2 and 3 hepatitis C, including people with cirrhosis, planned for second half of 2013-

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced it has entered into a non-exclusive agreement with Bristol-Myers Squibb Company (NYSE: BMY) to conduct Phase 2 studies of once-daily all-oral treatment regimens containing Vertex's nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir for the treatment of hepatitis C. As part of the agreement, Vertex plans to conduct two Phase 2 studies of the combination, including an initial study in treatment-naïve people with genotype 1 HCV infection planned for the second quarter of 2013. Vertex plans to begin a subsequent study in treatment-naïve people infected with genotype 1, 2 or 3 HCV, including those with cirrhosis, in the second half of 2013, pending data from the initial study.

"With more than 170 million people infected worldwide, there is a critical need for new hepatitis C medicines that can offer people simpler and more tolerable treatment regimens that provide high cure rates," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "These studies with daclatasvir will provide the first opportunity to evaluate VX-135 as part of all-oral regimens in people with multiple hepatitis C genotypes and in people with cirrhosis."

Clinical Development Plans for VX-135 with Daclatasvir

Under the terms of the agreement, Vertex will conduct two Phase 2 studies of VX-135 in combination with daclatasvir. The first study will enroll approximately 20 non-cirrhotic, treatment-naïve people with chronic genotype 1 HCV infection and is expected to begin in the second quarter of 2013. In the second half of 2013, Vertex plans to conduct a subsequent study in approximately 250 treatment-naïve people with chronic genotype 1, 2 or 3 HCV infection, including those with cirrhosis. Each of these studies is expected to evaluate safety, tolerability, pharmacokinetics and viral cure rates (SVR4 and SVR12) of multiple all-oral regimens of VX-135 and daclatasvir dosed once daily, pending regulatory discussions. Vertex will also conduct co-formulation activities to evaluate the potential for development of a once-daily fixed-dose combination regimen. Further clinical development activities beyond the Phase 2 studies are not covered as part of this agreement.

About VX-135

VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In people with genotype 1, treatment with a 200mg once-daily dose of VX-135 in a 7-day viral kinetic study was well-tolerated, with no discontinuations due to adverse events, and resulted in a 4.54 log10 median reduction from baseline in HCV RNA. Data from a 7-day viral kinetic study of VX-135 in people with genotypes 2, 3 and 4 were consistent with data observed in people with genotype 1 and have been submitted for presentation at a future medical meeting.

Vertex gained worldwide rights to ALS-2200, known as VX-135 in Phase 2 studies, through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that focuses on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

About Daclatasvir

Daclatasvir is an NS5A replication complex inhibitor that is being extensively studied as a key component of potential DAA-based hepatitis C treatment regimens. Studied in more than 4,100 patients to date, daclatasvir is in Phase 3 development.

Daclatasvir is part of a portfolio of investigational compounds with different mechanisms of action that Bristol-Myers Squibb is developing for the treatment of hepatitis C. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.

About Hepatitis C

Hepatitis C is a serious liver infection caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1 Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.3,4

More than 170 million people worldwide are chronically infected with hepatitis C.5 In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.6,7 Hepatitis C is four times more prevalent in the United States compared to HIV.7 The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting for three fourths of people with the infection.8 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.9,10 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the second paragraph of the press release and statements regarding Vertex's expectations with respect to the timing and structure of studies evaluating the combination of VX-135 and daclatasvir. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the initiation of planned studies may be delayed or prevented, that the outcomes of Vertex's planned clinical studies may not be favorable and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

References:

1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed September 21, 2012.

2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

3 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

4 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

6 Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.

7 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed September 21, 2012.

8 Centers for Disease Control and Prevention. Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945—1965. Morbidity and Mortality Weekly Report. August 17, 2012; 61(RR04);1-18.

9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

10 Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

11 Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009. Available at: http://www.vrtx.com/assets/pdfs/MillimanReport.pdf

VRTX — GEN


Vertex Pharmaceuticals Incorporated
Media:
Zach Barber, 617-341-6470
mediainfo@vrtx.com
or
Investors:
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Source: Vertex Pharmaceuticals Incorporated

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Vertex Signs Deal With Bristol-Myers for Hepatitis C Treatment Studies

Vertex Pharmaceuticals Inc. (VRTX) entered a nonexclusive agreement with Bristol-Myers Squibb Co. (BMY) to conduct midstage studies for hepatitis C treatments, its latest collaboration as part of its push to develop treatments for the liver disease.

The Phase 2 studies are for once-daily all-oral treatment regimens containing Vertex's nucleotide analogue hepatitis C virus polymerase inhibitor VX-135 and Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir.

As part of the agreement, Vertex plans to conduct two Phase 2 studies of the combination, including an initial study in treatment-naive people with genotype 1 hepatitis C virus, planned for the second quarter.

Vertex plans to begin a subsequent study in treatment-naive people infected with genotype 1, 2 or 3 hepatitis C virus, including those with cirrhosis, in the second half, pending data from the initial study.

"With more than 170 million people infected worldwide, there is a critical need for new hepatitis C medicines that can offer people simpler and more tolerable treatment regimens that provide high cure rates," Vertex Chief Medical Officer Robert Kauffman said. "These studies with daclatasvir will provide the first opportunity to evaluate VX-135 as part of all-oral regimens in people with multiple hepatitis C genotypes and in people with cirrhosis."

Treatments for hepatitis C are considered lucrative because the disease is prevalent in large sections of the global population. The virus, which can be transmitted sexually or through use of shared needles and at tattoo parlors, affects some 170 million people world-wide.

Both Vertex and Bristol-Myers have grappled with setbacks in their push to develop treatments for hepatitis C. In August, Bristol-Myers said it had suspended its study of a drug intended to treat hepatitis C after a patient suffered heart failure, which the company called a "serious safety issue."

Meanwhile in December, the Food and Drug Administration placed a new label on Vertex's hepatitis C drug Incivek, warning patients that the drug has caused fatal skin rashes in some patients.

The latest collaboration comes after Vertex in November teamed up with two rivals to study potential new treatments for hepatitis C. In separate partnerships, Vertex said it would begin mid-stage trials in 2013 to study its investigational drug VX-135 in combination with treatments being developed by GlaxoSmithKline PLC (GSK) and Johnson & Johnson's (JNJ) Janssen Pharmaceuticals unit.

Shares of Vertex closed Thursday at $52.95, while those of Bristol-Myers closed at $40.78. Both stocks were inactive premarket.

Write to Saabira Chaudhuri at saabira.chaudhuri@dowjones.com

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Sunday, January 6, 2013

Hepatitis C: Vertex's strategy in hepatitis C is to develop new all-oral treatment regimens

press release
Jan. 6, 2013, 5:00 p.m. EST

Vertex Outlines Corporate Strategy and Defines Key 2013 Business Priorities

-2013 investment focused on key development programs in cystic fibrosis, hepatitis C and autoimmune diseases-

Hepatitis C

-- Hepatitis C: Vertex's strategy in hepatitis C is to develop new all-oral treatment regimens of 12 weeks or less in duration with a goal of providing a high viral cure rate and improved tolerability. In 2013, Vertex plans to conduct multiple Phase 2 studies of 12-week all-oral treatment regimens that include the company's nucleotide analogue VX-135. These studies are expected to provide safety and viral cure rate data in the second half of 2013 to support the start of pivotal development of one or more all-oral regimens in 2014.

Vertex plans to initiate multiple studies of the nucleotide analogue VX-135 as part of 12-week all-oral combination treatment regimens. Vertex expects to generate data from these studies in the second half of 2013 to enable progression into pivotal development in 2014. The all-oral studies for VX-135 include:

VX-135 in Combination with Ribavirin

-- In the first quarter of 2013, Vertex expects to begin dosing in a study of VX-135 and ribavirin as part of a 12-week all-oral treatment regimen. The study will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment).

Collaborative Agreements for All-Oral Studies of VX-135

-- In late 2012, Vertex entered into two non-exclusive agreements to conduct Phase 2 proof-of-concept studies of VX-135 in combination with simeprevir (TMC435), a once-daily protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB, and with GSK2336805, a once-daily NS5A inhibitor in development by GlaxoSmithKline (GSK). These Phase 2 studies will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment) using 12-week combination regimens. A drug-drug interaction study with simeprevir will be initiated shortly, and Vertex expects the Phase 2 studies to be initiated in the first half of the year.
 
SAN FRANCISCO, Jan 06, 2013 (BUSINESS WIRE) -- ---First two Breakthrough Therapy Designations from U.S. FDA granted to ivacaftor monotherapy and to the combination regimen of VX-809 and ivacaftor for the treatment of cystic fibrosis-

Vertex Pharmaceuticals Incorporated /quotes/zigman/79675/quotes/nls/vrtx VRTX +1.55% today outlined the company's strategy and defined key 2013 business priorities to support continued growth and the creation of long-term shareholder value. Vertex's Chairman, President and Chief Executive Officer, Jeffrey Leiden, M.D., Ph.D., will discuss the company's strategy and 2013 priorities as part of a live presentation at the 31st Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 7 at 10:00 a.m. PT (1:00 p.m. ET). The presentation will be webcast on Vertex's website, www.vrtx.com .

"Since the approval of our first medicine less than two years ago, Vertex has undergone a rapid evolution that has positioned the company to move forward with a clear focus on using innovative science to develop transformative medicines for serious diseases in specialty markets," said Dr. Leiden.

"In cystic fibrosis and hepatitis C, KALYDECO and INCIVEK are just the beginning of what we hope to provide to people with these diseases. In CF, multiple ongoing and planned studies of KALYDECO monotherapy and other combinations of our CF medicines in development aim to help many more people with this disease. In hepatitis C, we are focused on developing multiple all-oral regimens that could further improve treatment. In addition to our development programs, we continue to invest in research for future medicines, with a focus on serious diseases where we have significant scientific expertise and commercial capabilities."

Entering 2013, Vertex's key strategies and business priorities include:

1. Focusing investment on key development programs for:

-- Cystic Fibrosis (CF): Vertex's CF strategy is to provide benefit to as many CF patients as possible, and to maximize the benefit for these patients, with our approved and investigational medicines. KALYDECO(TM) (ivacaftor) is currently approved for people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene (approximately 2,000 people with CF worldwide). In 2013, the company is conducting multiple Phase 3 label-expansion and other proof-of-concept studies of ivacaftor monotherapy in people with certain mutations not studied in prior Phase 3 studies. Vertex also expects to initiate a pivotal Phase 3 development program for a combination regimen of VX-809 and ivacaftor in people with CF who have two copies of the F508del mutation in the first quarter of 2013.

-- Hepatitis C: Vertex's strategy in hepatitis C is to develop new all-oral treatment regimens of 12 weeks or less in duration with a goal of providing a high viral cure rate and improved tolerability. In 2013, Vertex plans to conduct multiple Phase 2 studies of 12-week all-oral treatment regimens that include the company's nucleotide analogue VX-135. These studies are expected to provide safety and viral cure rate data in the second half of 2013 to support the start of pivotal development of one or more all-oral regimens in 2014.

-- Autoimmune Diseases: Vertex's strategy in autoimmune diseases is to maximize the value of VX-509 across multiple autoimmune diseases globally. The company will evaluate collaborative opportunities that provide funding and capabilities to broaden and accelerate global development of VX-509.

2. Investing in innovative research programs to support development of additional specialty medicines for serious diseases

-- Vertex's research efforts are concentrated on additional advancements in CF and other genetic diseases and additional serious diseases in specialty markets.

3. Maximizing revenues and cash flow from the appropriate use of INCIVEK(R) (telaprevir) and KALYDECO in the U.S. and Canada and from the growth of KALYDECOin Europe and other countries

4. Maintaining financial strength to support future growth and shareholder returns

Cystic Fibrosis

In CF, Vertex is rapidly advancing multiple studies aimed at expanding the number of people who may benefit from our approved and investigational CF medicines, including ivacaftor monotherapy for people with certain mutations not evaluated in prior studies and a combination of VX-809 and ivacaftor in people with two copies of the F508del mutation. The company also is advancing its second-generation corrector research program, which may lead to further improvements in CF treatment in the coming years. Vertex today provided the following updates to its CF development program:

Vertex Receives First Two Breakthrough Therapy Designations from U.S. FDA

-- Vertex today announced that the U.S. Food and Drug Administration (FDA) granted the first two Breakthrough Therapy Designations to ivacaftor monotherapy and the combination regimen of VX-809 with ivacaftor for CF. Enacted as part of the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA), Breakthrough Therapy Designation is intended to expedite the development and review of a potential new medicine if it is "intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development."(1)

-- The FDA granted Breakthrough Therapy Designation to ivacaftor for potential additional indications beyond the currently approved use of this medicine for people with CF ages 6 and older who have the G551D mutation. The designation for ivacaftor was based on data from clinical and pre-clinical studies, including Phase 3 data in people with the G551D mutation and pre-clinical data in the G551D mutation as well as a number of other mutations. The Breakthrough Therapy Designation for the combination regimen of VX-809 with ivacaftor was based on the Phase 2 combination data announced in 2012. Multiple studies are currently underway in an effort to determine whether patients with other CFTR mutations may benefit from ivacaftor alone, and Vertex is also preparing to start a pivotal program of VX-809 in combination with ivacaftor in people who have two copies of the most common CF mutation (F508del).

-- The implications of Breakthrough Therapy Designation cannot be determined at this time. Vertex is working with the FDA and other global regulatory agencies to determine any potential implications of the Breakthrough Therapy Designations to its ongoing and planned development activities, and subsequent regulatory submissions, for ivacaftor monotherapy and the combination regimen of VX-809 with ivacaftor.

KALYDECO (ivacaftor) Reimbursement Progress in Europe

-- Since approval of KALYDECO in January 2012, the vast majority of the eligible patients with the G551D mutation in the U.S. have initiated treatment with KALYDECO. Growth in 2013 KALYDECO revenues will be dependent on completion of reimbursement discussions in other countries outside the U.S. The company is now seeking reimbursement for KALYDECO in multiple countries in Europe. In December, the National Health Service (NHS) recommended funding of KALYDECO in England. In England, Vertex will make ivacaftor available to eligible people with CF as quickly as possible as part of a patient access program with the NHS and anticipates reimbursement to begin in the second quarter of 2013.

Ivacaftor Label-Expansion Studies

-- There are three Phase 3 label expansion trials and one Phase 2 proof-of-concept study underway for ivacaftor monotherapy: -- A Phase 3 study of ivacaftor is ongoing in people with CF ages 6 and older who have at least one copy of the R117H mutation. Approximately 3 percent of people with CF in the U.S. have at least one R117H mutation.

-- A Phase 3 study of ivacaftor is ongoing in people with CF ages 6 and older who have at least one non-G551D CFTR gating mutation. Approximately 1 percent of people with CF in the U.S. have at least one non-G551D gating mutation.

-- A Phase 3 study of ivacaftor was recently initiated in children with CF ages 2 to 5 who have a gating mutation. Enrollment of this study is underway.

-- A Phase 2 proof-of-concept study is underway evaluating ivacaftor in people with CF who have clinical evidence of residual CFTR function. This is the first study to evaluate the safety and efficacy of ivacaftor based on a person's clinical symptoms and characteristics, or phenotype, rather than solely on their CFTR mutation, or genotype. Between 5 and 10 percent of people with CF in the U.S. may have residual CFTR function.

-- Vertex expects to obtain the first data from these studies in the second half of 2013. In 2013, Vertex expects to discuss with the U.S. FDA any potential implications of Breakthrough Therapy Designation on the timing and content of regulatory submissions in the U.S. to support expansion of the KALYDECO label. The company will also discuss plans for submission of these data with other global regulatory authorities.

Combination of VX-809 and ivacaftor for People with Two Copies of the F508del Mutation

-- Vertex recently completed an end-of-Phase 2 meeting with the FDA and is on track to submit final protocols and initiate a pivotal Phase 3 program of VX-809 in combination with ivacaftor in the first quarter of 2013, pending regulatory approval.

Combination of VX-661 and ivacaftor for People with Two Copies of the F508del Mutation

-- A Phase 2 study of VX-661 and ivacaftor is ongoing in people with two copies of the F508del mutation. Data from this study are expected in the first half of 2013.

Research to Identify Additional CF Treatment Regimens

-- Vertex has an active and ongoing research program that has identified next-generation correctors. This research is being conducted as part of the company's collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., and is focused on the accelerated discovery and development of correctors that could play a role in a variety of future combination treatments, including a dual corrector approach, among others.

Hepatitis C

In hepatitis C, Vertex plans to initiate multiple studies of the nucleotide analogue VX-135 as part of 12-week all-oral combination treatment regimens. Vertex expects to generate data from these studies in the second half of 2013 to enable progression into pivotal development in 2014. The all-oral studies for VX-135 include:

VX-135 in Combination with Ribavirin

-- In the first quarter of 2013, Vertex expects to begin dosing in a study of VX-135 and ribavirin as part of a 12-week all-oral treatment regimen. The study will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment).

Collaborative Agreements for All-Oral Studies of VX-135

-- In late 2012, Vertex entered into two non-exclusive agreements to conduct Phase 2 proof-of-concept studies of VX-135 in combination with simeprevir (TMC435), a once-daily protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB, and with GSK2336805, a once-daily NS5A inhibitor in development by GlaxoSmithKline (GSK). These Phase 2 studies will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment) using 12-week combination regimens. A drug-drug interaction study with simeprevir will be initiated shortly, and Vertex expects the Phase 2 studies to be initiated in the first half of the year.

Autoimmune Diseases

In mid-2012, Vertex initiated a Phase 2b study of VX-509, a selective JAK3 inhibitor, in people with moderate to severe rheumatoid arthritis (RA). This study is ongoing, with data expected in the second half of 2013. Vertex believes there is a global opportunity for VX-509 to treat multiple autoimmune diseases. Vertex will evaluate collaborative opportunities that would enable the company to maximize the value of VX-509 by providing funding and capabilities to broaden and accelerate the company's evaluation of VX-509 across multiple additional autoimmune diseases globally.

Financial Strength to Invest in Research Innovation and Development of New Medicines

Vertex plans to announce fourth quarter and full-year 2012 financial results, and 2013 financial guidance, in late January. The company expects total non-GAAP operating expenses (that exclude cost of revenues, stock-based compensation expense, and Alios expenses related to the collaboration with Vertex) for 2013 to be similar to 2012. We anticipate a reduction in our 2013 SG&A expenses compared to 2012. The company's 2013 R&D expenses will primarily support:

-- Investment in broad development activities for our late-stage CF and hepatitis C programs, including formulation and commercial supply chain investment

-- Completion of Phase 2 evaluation of VX-509 in RA

-- Investment in research programs aimed at the creation of future medicines

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Indication and Important Safety Information for KALYDECO (ivacaftor)

Ivacaftor (150mg tablets) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the CFTR gene.

Ivacaftor is not for use in people with CF due to other mutations in the CFTR gene. It is not effective in CF patients with two copies of the F508del mutation (F508del/F508del) in the CFTR gene. The efficacy and safety of ivacaftor in children younger than 6 years of age have not been evaluated.

High liver enzymes (transaminases, ALT and AST) have been reported in patients receiving ivacaftor. It is recommended that ALT and AST be assessed prior to initiating ivacaftor, every 3 months during the first year of treatment, and annually thereafter. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal. Following resolution of transaminase elevations, consider the benefits and risks of resuming ivacaftor dosing. Moderate transaminase elevations are common in subjects with CF. Overall, the incidence and clinical features of transaminase elevations in clinical trials was similar between subjects in the ivacaftor and placebo treatment groups. In the subset of patients with a medical history of elevated transaminases, increased ALT or AST have been reported more frequently in patients receiving ivacaftor compared to placebo.

Use of ivacaftor with medicines that are strong CYP3A inducers such as the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John's Wort substantially decreases exposure of ivacaftor, which may diminish effectiveness. Therefore, co-administration is not recommended.

The dose of ivacaftor must be adjusted when concomitantly used with potent and moderate CYP3A inhibitors. The dose of ivacaftor must be adjusted when used in patients with moderate or severe hepatic disease.

Ivacaftor can cause serious adverse reactions including abdominal pain and high liver enzymes in the blood. The most common side effects associated with ivacaftor include headache; upper respiratory tract infection (the common cold), including sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; and dizziness. These are not all the possible side effects of ivacaftor. A list of the adverse reactions can be found in the full product labeling for each country where ivacaftor is approved. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full U.S. Prescribing Information for KALYDECO at www.KALYDECO.com , the EU Summary of Product Characteristics for KALYDECO at http://goo.gl/N3Tz4 , and the KALYDECO Canadian Product Monograph at www.vrtx.ca .

Indication and Important Safety Information for INCIVEK (telaprevir)

INCIVEK(R) (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK(R) (telaprevir) should always be used in combination with peginterferon alfa and ribavirin. INCIVEK combination treatment may cause serious side effects including skin rash and serious skin reactions, anemia (low red blood cell count) that can be severe, and birth defects or death of an unborn baby.

Skin rashes are common with INCIVEK combination treatment. Sometimes these skin rashes and other skin reactions can become serious, require treatment in a hospital, and may lead to death. Patients should call their healthcare provider right away if they develop any skin changes during treatment with INCIVEK. Their healthcare provider will decide if they need treatment or if they need to stop INCIVEK or any of their other medicines. Patients should not stop taking INCIVEK combination treatment without talking with their healthcare provider first.

Patients' healthcare providers will do blood tests regularly to check for anemia. If anemia is severe, the healthcare providers may tell them to stop taking INCIVEK.

INCIVEK combined with peginterferon alfa and ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Females who can become pregnant and females whose male partner takes these medicines must have a negative pregnancy test before starting treatment, every month during treatment, and for 6 months after treatment ends. Patients must use two forms of effective birth control during treatment and for 6 months after all treatment has ended. These two forms of birth control should not contain hormones, as these may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life-threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

The most common side effects of INCIVEK combination treatment include itching, nausea, diarrhea, vomiting, anal or rectal problems (including hemorrhoids, discomfort, burning or itching around or near the anus), taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare provider about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information including Boxed Warning, and the Medication Guide for INCIVEK available at www.INCIVEK.com .

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Leiden's statements in the second and third paragraphs of the press release, the information provided in the four numbered key strategies and business priorities for 2013 and statements regarding (i) Vertex rapidly advancing multiple studies aimed at expanding the number of people who may benefit from our approved and investigational CF medicines and Vertex's CF research program; (ii) expectations regarding the submission of final protocols and the initiation of a pivotal Phase 3 program of VX-809 in combination with ivacaftor; (iii) the dependence of growth in KALYDECO revenues in 2013 on the completion of reimbursement discussions in countries outside the U.S. and the anticipation that reimbursement in England will begin in the second quarter of 2013; (iv) expectations regarding the timing and structure of all-oral studies of VX-135; (v) information regarding the company's ongoing and planned studies and the timing of the availability of data from these studies; (vi) the expectation that Vertex will generate data from studies of VX-135 in the second half of 2013 to enable progression into pivotal development in 2014; (vii) potential collaborative opportunities and (viii) expectations regarding 2013 non-GAAP operating expenses. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the company's expectations regarding future KALYDECO revenues and/or operating expenses may be incorrect, that the outcomes of Vertex's ongoing and planned clinical studies may not be favorable, that the initiation of planned studies and/or pivotal programs may be delayed or prevented, that collaborative arrangements may not be available on acceptable terms and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com . Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

Saturday, November 10, 2012

AASLD- ALS-2200 (VX-135), Vertex's Oral Nucleotide Analogue in Development for Hepatitis C

Data from Viral Kinetic Study Showed Rapid Reduction of HCV RNA with ALS-2200 (VX-135), Vertex's Oral Nucleotide Analogue in Development for the Treatment of Hepatitis C

BOSTON --(Business Wire)--
Vertex (News - Alert) Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that data on ALS-2200 (VX-135), an oral medicine Vertex is developing for the treatment of hepatitis C, are being presented for the first time at The Liver Meeting®, the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

There was a median 4.54 log10 reduction (range -3.81, -5.08) in hepatitis C virus (HCV) RNA after seven days of dosing with ALS-2200 (200 mg) once daily in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Similar reductions in HCV RNA were seen in a seven-day viral kinetic study of once daily ALS-2200 (200 mg) in combination with ribavirin (n=8). ALS-2200 was well-tolerated in this study, with no serious adverse events and no discontinuations due to adverse events.

Based on these data, and to further characterize the medicine's safety and efficacy profile, Vertex plans to begin multiple Phase 2 studies of 12-week all-oral regimens in people with genotype 1 hepatitis C in early 2013, pending discussions with regulatory authorities. These studies will include combinations of VX-135 with GSK2336805 and separately with simeprevir (TMC435). Upon the start of Phase 2 studies, ALS-2200 will be known as VX-135. Screening in the first study, which will evaluate VX-135 in combination with ribavirin, is expected to begin in the coming weeks.

"We're working quickly to evaluate multiple all-oral treatment regimens with VX-135 and expect to have a significant amount of data from several Phase 2 studies by the end of 2013," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "Our goal is to proceed to pivotal development with one or more regimens that have the greatest potential to offer doctors and the people they treat a more tolerable, short-duration therapy with high viral cure rates for hepatitis C."

Seven-day viral kinetic data showed that when once-daily ALS-2200 (200 mg) was dosed in combination with ribavirin, there was a median 4.18 log10 reduction (range -3.6, -5.2) in HCV RNA in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Five patients achieved HCV RNA levels below the limit of quantification (< LOQ = < 25 IU/mL), and two of these five achieved HCV RNA levels below the limit of detection (Roche COBAS Taqman HCV test, Version 2) after seven days of dosing. Similar to the data from the monotherapy cohort, ALS-2200 in combination with ribavirin was well-tolerated, no patients discontinued due to adverse events and there were no serious adverse events.

"The early antiviral activity and tolerability of this nucleotide analogue are very promising as we seek to develop new interferon-free treatment regimens," said Patrick Marcellin, M.D., Ph.D., Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "The data suggest VX-135 could be a core component of all-oral regimens for the treatment of hepatitis C."

"Preclinical characterization of ALS-2200, a potent nucleotide polymerase inhibitor for the treatment of chronic hepatitis C."
Poster presentation #1882
November 13, 2012, 8:00 a.m. - 12:00 p.m. EST
Preclinical data on ALS-2200 will be presented at AASLD that support the Phase 1 viral kinetic study and further clinical development plans. In preclinical studies, ALS-2200 was shown to be a potent, selective, specific, and pan-genotypic nucleotide analogue that inhibits the HCV NS5B polymerase. Specifically, there was no in vitro inhibition of non-HCV viruses, human DNA (ß or ?) or RNA (II) polymerases, or mitochondrial protein synthesis. The studies also showed that ALS-2200 retains potency in vitro against a panel of HCV variants resistant to NS3/4A, NS5A and non-nucleoside NS5B inhibitors.

"Analysis of ALS-2200, a novel potent nucleotide analog, combination drug interactions in the hepatitis C virus (HCV) subgenomic replicon system."
Poster presentation #1887
November 13, 2012, 8:00 a.m. - 12:00 p.m. EST
Combination studies with ALS-2200 were performed in vitro to determine whether interactions with other drugs were additive, synergistic or antagonistic. Combination of ALS-2200 with either telaprevir or VX-222 demonstrated a synergistic effect, and combination with ribavirin resulted in an additive response. No significant cytotoxicity or antagonism were observed at any concentration of the combinations tested. Combinations of ALS-2200 and 18 other compounds were also tested, including simeprevir, which showed significant synergy with ALS-2200.
"We're pleased with the strength of our collaboration with Vertex and how it may lead to advances in the treatment of hepatitis C," said Lawrence M. Blatt, Ph.D., Founder, President and Chief Executive Officer of Alios BioPharma. "We're looking forward to seeing the results of several studies evaluating various all-oral combinations including VX-135."

VX-135 Phase 2 Trials
Vertex recently announced that it has entered into two non-exclusive agreements to conduct Phase 2 proof-of-concept studies of VX-135 in combination with simeprevir (TMC435), a protease inhibitor being jointly developed by Janssen R&D Ireland and Medivir AB, and with GSK2336805, an NS5A inhibitor in development by GlaxoSmithKline (GSK). The studies with GSK2336805 and simeprevir are expected to begin in early 2013, pending discussions with regulatory authorities. Screening is expected to begin in the coming weeks for a Phase 2 study of VX-135 and ribavirin. Vertex also plans to begin a study of VX-135 and telaprevir, the company's approved protease inhibitor marketed as INCIVEK®(telaprevir) tablets for people with chronic genotype 1 hepatitis C, in early 2013, pending discussions with regulatory authorities. All of these Phase 2 studies will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end of treatment) using 12-week combination regimens.

About VX-135 (ALS-2200)
VX-135 (ALS-2200) is a uridine nucleotide analogue pro-drug that appears to have a high barrier to drug resistance based on in vitro studies. It is designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In vitro studies of the compound showed antiviral activity across all genotype, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.

Vertex gained worldwide rights to ALS-2200 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that focuses on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

About INCIVEK
INCIVEK® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK has been prescribed to more than 50,000 patients in the United States. Approximately three out of four U.S. patients who are prescribed a direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C (HCV) receive INCIVEK combination therapy.

In Phase 3 clinical studies, 79 percent of people who had not previously been treated for HCV achieved a viral cure following treatment with INCIVEK combination therapy, compared with 46 percent of those who received pegylated-interferon and ribavirin (P/R) alone. Among people who were treated previously but did not achieve a viral cure, in the Phase 3 studies: 86 percent of relapsers achieved a viral cure with INCIVEK combination therapy compared to 22 percent with P/R alone; 59 percent of partial responders achieved a viral cure compared with 15 percent with P/R alone; and 32 percent of null responders achieved a viral cure compared with 5 percent with P/R alone. In addition, many people are eligible to complete treatment with INCIVEK combination therapy in 24 weeks - half the time required for P/R alone.

INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for adults with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).

Vertex developed telaprevir in collaboration with Janssen and Mitsubishi (News - Alert) Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic®.

Continue reading @ http://technews.tmcnet.com/news/2012/11/10/6715418.htm

Thursday, November 1, 2012

Vertex Joins Glaxo, J&J in Testing Hepatitis C Combos


Vertex Joins Glaxo, J&J in Testing Hepatitis C Combos
By Meg Tirrell on November 01, 2012

Source - Bloomberg

Vertex Pharmaceuticals Inc. (VRTX), maker of the hepatitis C drug Incivek, said it agreed to test one of its experimental therapies for the disease with other drugs from Johnson & Johnson (JNJ) and GlaxoSmithKline Plc. (GSK)

The drug, VX-135, will be tested with J&J’s simeprevir and Glaxo’s GSK2336805 in separate 12-week trials to determine whether the combinations help rid patients of the virus, Cambridge, Massachusetts-based Vertex said in two statements today. The companies will split development costs with Vertex.

Vertex Chief Executive Officer Jeffrey Leiden said in an interview last month that the company had been drawing collaborator interest for VX-135, one of the last viable experimental therapies in a class called nucleotides thought to be an important part of combination therapy to treat hepatitis C. The disease affects an estimated 170 million people worldwide, and drugmakers have been rushing to bring to market next-generation therapies that don’t require injections.

“We view this as a best case path forward for Vertex, as it allows the company to explore VX-135 with two different classes, partnered with major pharmaceutical companies who are fairly dependent on the success of these respective combinations to remain competitive in the all-oral hepatitis-C virus race,”Brian Abrahams, an analyst with Wells Fargo Securities, wrote in a research note today.

The drug combinations will be tested in the second of three stages of clinical trials generally required for regulatory approval. J&J’s drug, partnered with Sweden’s Medivir AB (MVIRB), is in a class of therapies called protease inhibitors, which includes Incivek, also known as telaprevir. Glaxo’s drug is in a class called NS5A inhibitors.

Combination Therapy
Combinations of different kinds of drugs are thought to be the most effective way to combat hepatitis C because they strike at the various ways the virus infects the body. Gilead Sciences Inc. (GILD), Abbott Laboratories (ABT) and Bristol-Myers Squibb Co. (BMY) are among other drugmakers testing therapies for the disease.

Vertex rose 3.5 percent to $49.98 at 9:48 a.m. in New York trading, after increasing 45 percent this year through yesterday. The shares of New Brunswick, New Jersey-based J&J, which has a partnership with Vertex already on Incivek, gained less than 1 percent to $71.07. Glaxo rose 0.3 percent to 1,391 pence in London.

Vertex also plans to test VX-135 in combination with its own therapies, Incivek and the experimental medicine VX-222, Leiden said last month. The company licensed VX-135 from Alios BioPharma Inc. along with another nucleotide, ALS-2158. Vertex discontinued development of the second compound in September for lack of efficacy.

“This is a good move for Vertex and should help quell concerns from some investors that the company wanted to prioritize Incivek combo regimens,” Mark Schoenebaum, an analyst with ISI Group in New York, wrote in a note to clients today. “Recall, however, that there is very little data available for Vertex’s nuc at this point - thus development risk remains high.”

To contact the reporter on this story: Meg Tirrell in New York at mtirrell@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Source - Bloomberg

Related -Hepatitis C: Vertex Enters Agreement with GlaxoSmithKline - Phase 2 All-Oral Study of VX-135 and GSK2336805

 Hepatitis C: Vertex Announces Collaboration with Janssen - Phase 2 All-Oral Study of VX-135 and Simeprevir (TMC435)



Hepatitis C: Vertex Announces Collaboration with Janssen - Phase 2 All-Oral Study of VX-135 and Simeprevir (TMC435)

November 1, 2012
 
Vertex Announces Collaboration with Janssen To Initiate Phase 2 All-Oral Study of VX-135 and Simeprevir (TMC435) for the Treatment of Hepatitis C

-Companies to evaluate two-drug combination of Vertex's investigational nucleotide analogue VX-135 and Janssen's investigational protease inhibitor simeprevir (TMC435)-
 
-Phase 2 proof-of-concept study to begin in early 2013 to evaluate safety, tolerability and viral cure rates of 12-week treatment regimen-
 
CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that it has entered into a non-exclusive collaboration with Janssen Pharmaceuticals, Inc. to conduct a Phase 2 proof-of-concept study of an all-oral regimen for the treatment of hepatitis C containing Vertex's nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135 and Janssen's protease inhibitor simeprevir (TMC435). As part of the collaboration, Janssen will conduct a drug-drug interaction study with VX-135 and simeprevir to support the planned initiation of a Phase 2 proof-of-concept study in early 2013, pending discussions with regulatory authorities. The Phase 2 study is expected to evaluate safety, tolerability and viral cure rates using a 12-week combination of VX-135 and simeprevir. The companies will jointly fund development costs associated with the collaboration. There are no up-front or milestone payments associated with the agreement. VX-135 is an investigational uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Simeprevir is a potent, once-daily investigational hepatitis C protease inhibitor, currently in Phase 3 trials, being jointly developed by Janssen R&D Ireland and Medivir AB.
  
"This collaboration is an important step forward in our commitment to develop new all-oral treatment regimens for people with hepatitis C — both in collaboration with other companies like Janssen and with medicines within our own pipeline," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "We believe that an all-oral regimen of VX-135 and simeprevir has the potential to achieve high cure rates with only 12 total weeks of treatment for people with hepatitis C, and we look forward to the start of the Phase 2 proof-of-concept study with Janssen."
   
Clinical Development Plans
Vertex and Janssen expect to initiate a Phase 2 proof-of-concept study of VX-135 and simeprevir in early 2013, following the completion of a drug-drug interaction (DDI) study and pending discussions with regulatory authorities. Costs associated with the studies will be shared equally between the two companies. The goals of the study will be to evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end treatment) of multiple 12-week combination regimens of VX-135 and simeprevir, with and without ribavirin, in people who have chronic non-cirrhotic genotype 1 hepatitis C and have not previously been treated (treatment-naïve). Further clinical development activities beyond the Phase 2 proof-of-concept study are not covered as part of this collaboration. Additional information on the Phase 2 study will be provided upon initiation of the study.
  
About VX-135
VX-135 (ALS-2200) is a uridine nucleotide analogue pro-drug that appears to have a high barrier to drug resistance based on in vitro studies. It is designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In vitro studies of the compound showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.
  
Earlier this year, Vertex announced the first 7-day viral kinetic data for VX-135. Based on these data, the company plans to initiate multiple all-oral, Phase 2 proof-of-concept studies, including a study of VX-135 and ribavirin and a study of VX-135 and telaprevir, the company's approved protease inhibitor marketed as INCIVEK for people with chronic genotype 1 hepatitis C. Vertex is on track to initiate the study of VX-135 in combination with ribavirin by the end of 2012, followed by the study with telaprevir in early 2013. The studies will evaluate safety, tolerability and viral cure rates (SVR12; undetectable hepatitis C virus 12 weeks after the end treatment) of 12-week combination regimens in people with chronic non-cirrhotic genotype 1 hepatitis C who have not previously been treated (treatment-naïve).
  
Vertex gained worldwide rights to VX-135 through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.
  
About Simeprevir (TMC435)
Simeprevir is a once-daily potent investigational hepatitis C protease inhibitor in late Phase 3 clinical development being jointly developed by Janssen R&D Ireland and Medivir AB to treat chronic hepatitis C virus infections. Simeprevir is being investigated in combination with PegIFN/RBV in Phase 3 trials and is also being evaluated with Direct-acting Antiviral (DAA) agents in three other Phase 2 interferon-free combinations both with and without ribavirin (RBV). For further details please visit http://www.medivir.com.
  
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1

Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8

More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9,10 Hepatitis C is four times more prevalent in the United States compared to HIV.10 The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting for 82 percent of people with the disease.11 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.12,13 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.10

About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.
  
About Janssen
At Janssen we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland and Janssen Pharmaceuticals, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.
  
IMPORTANT SAFETY INFORMATION FOR INCIVEK
Indication
INCIVEK® (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
  
Important Safety Information:
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.
  
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
  
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
  
References:
1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed September 21, 2012.
2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
9 Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.
  
10 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed September 21, 2012.
11 Smith, BD, et al. Hepatitis C Virus Antibody Prevalence, Correlates and Predictors among Persons Born from 1945 through 1965, United States, 1999-2008. AASLD 2011 Annual Meeting.
12 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
13 S.D. Holmberg, K.N. Ly., et.al. The Growing Burden of Mortality Associated with Viral Hepatitis in the United States, 1999-2007. AASLD 2011 Annual Meeting.
   
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the second paragraph of the press release and statements regarding Vertex's expectations with respect to the timing and structure of studies evaluating the combination of VX-135 and simeprevir (TMC435) and other planned all-oral Phase 2 studies with VX-135. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the initiation of planned studies may be delayed or prevented, that the outcomes of Vertex's planned clinical studies may not be favorable and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
  
VRTX — GEN

Vertex Pharmaceuticals Incorporated
Media:
Zach Barber, 617-444-6470
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Kelly Lewis, 617-444-7530
Source: Vertex Pharmaceuticals Incorporated

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