Hepatitis C Interferon-free: Late-breaking Abstracts Selected for Oral Presentation at The Liver Meeting®

Six Late-breaking Abstracts Selected for Oral Presentation at The Liver Meeting®

By American Association for the Study of Liver Diseases (AASLD)

American Association for the Study of Liver Diseases (AASLD)

Last modified: 2012-11-02T15:34:47Z

Published: Friday, Nov. 2, 2012 - 8:34 am

Read more here: http://www.sacbee.com/2012/11/02/4957094/six-late-breaking-abstracts-selected.html#storylink=cpy

BOSTON, Nov. 2, 2012 --
/PRNewswire/ --
Late-breaking Oral Session Monday, November 12, 2012 – 3:00-4:30 pm Auditorium, Hynes Convention Center

The six abstracts that will be presented at our late-breaking oral session relate to new therapies for patients with chronic liver diseases.

Four of the six studies (see numbers 1 - 4 below) report on the results of oral therapy for the treatment of hepatitis C, a disease that affects more than 3 million Americans and that is currently treated with weekly injections of a medication called interferon, in addition to pills. These studies show that almost all patients who receive these new pills (without interferon) eliminate the hepatitis C virus, even those who had not responded to interferon-based therapies. Given that these drugs are well-tolerated, these findings, if confirmed in longer follow up periods, can potentially lead to important changes in practice.

Viral hepatitis and other chronic liver diseases can lead to liver failure and/or liver cancer, requiring liver transplantation. After liver transplantation, one of the main complications is renal failure due to tacrolimus-based therapy to prevent rejection. The final results of a randomized study (see number 5 below) in patients with liver transplant shows that the addition of everolimus, another anti-rejection medication, allows us to minimize the dose of tacrolimus with comparable efficacy and better renal function.

Advanced unresectable liver cancer is currently treated with sorafenib, an oral anti-tumor medicine. A very large multinational, multicenter study (see number 6 below) enrolling over 1000 patients showed that brivanib was inferior to sorafenib in overall survival and was less well tolerated, and therefore sorafenib will continue to be the standard of care for these patients.

"We are living in very exciting times," says AASLD President Guadalupe Garcia-Tsao, MD. "While years ago there were no specific therapies for liver diseases, we now have many different therapies for patients with different types of liver disease and at different stages of disease. One of the most exciting areas is the therapy of hepatitis C, one of the main causes of liver disease in the world. At our late-breaking session, data will be presented on different therapeutic strategies that seem capable of eliminating the hepatitis C virus in practically all patients."

The following six studies will be presented at the late-breaking oral session:

1. A 12-Week Interferon-free Treatment Regimen with ABT-450/r, ABT-267, ABT-333 and Ribavirin Achieves SVR12 Rates (Observed Data) of 99% in Treatment-Naive Patients and 93% in Prior Null Responders with HCV Genotype1 InfectionA regimen of 3 direct acting antiviral medicines plus ribavirin was well tolerated and achieved high 12-week post-treatment viral elimination rates in both new patients and prior null responders with hepatitis C virus genotype 1 infection.
2. High Rate of Sustained Virologic Response with the All-Oral Combination of Daclatasvir (NS5A Inhibitor) Plus Sofosbuvir (Nucleotide NS5B Inhibitor), With or Without Ribavirin, in Treatment-Naive Patients Chronically Infected With HCV Genotype 1, 2, or 3A 24-week regimen of an all oral combination of once-daily daclatasvir (DCV) plus sofosbuvir (SOF) achieved high 12-week viral elimination rates in previously untreated patients infected with hepatitis C virus genotype 1, 2, or 3.
3. An Interferon-free, Ribavirin-free 12-Week Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 Yielded SVR4 of 94% in Treatment-Naive Patients with Genotype (GT) 1 Chronic Hepatitis C Virus (HCV) InfectionA 12-week interferon and ribavirin free regimen of three direct-acting antivirals, daclatasvir, asunaprevir, and BMS-791325 was well tolerated and achieved high 4-week post-treatment viral elimination rates in treatment-naive patients infected with hepatitis C virus genotype 1.
4. High Efficacy Of GS-7977 In Combination With Low or Full dose Ribavirin for 24 weeks In Difficult To Treat HCV Infected Genotype 1 Patients : Interim Analysis From The SPARE TrialA 24-week regimen of nucleotide NS5B inhibitor GS-7977 combined with low dose ribavirin was highly effective in suppressing hepatitis C virus replication in difficult to treat patients.
5. Everolimus-Facilitated Reduction Of Tacrolimus Provides Comparable Efficacy And Superior Renal Function Versus Standard Tacrolimus In De Novo Liver Transplant Recipients: 24-Month Results Of A Randomized Trial24-month results show that the minimization of tacrolimus (TAC) by introduction of everolimus (EVR) one month post liver transplant results in comparable overall efficacy and superior l renal function compared to standard TAC immunosuppression.
6. Brivanib (BRI) versus Sorafenib (SOR) as First-line Therapy in Patients with Unresectable, Advanced Hepatocellular Carcinoma (HCC): Results from the Phase 3 BRISK-FL StudyThe anti-tumor and anti-angiogenic drugbrivanib (BRI was less effective than sorafenib (SOR) when comparing overall survival rates in patients with advanced hepatocellular carcinoma, despite having a similar antitumor activity. BRI was also similar to SOR in terms of time to progression, objective response rate, and disease control rate but was less well-tolerated than SOR

Late-breaking abstracts contain research of new and sufficient scientific importance that merited special consideration after the standard abstract submission deadline. Late-breaking abstracts describe either large clinical studies or high-impact translational research that could not be completed prior to the original abstract submission deadline. The closure date of the study must have been March 21 or later with clinical trials (phase 2 or 3) being considered for oral presentation.

Founded in 1950, AASLD is the leading organization of scientists and health care professionals committed to preventing and curing liver disease. AASLD has grown into an international society responsible for all aspects of hepatology, and the annual meeting attracts 8,500 physicians, surgeons, researchers, and allied health professionals from around the world.

The Liver Meeting® is the premier meeting in the science and practice of hepatology, including the latest findings on new drugs, novel treatments, and the results from pilot and multicenter studies.

When: November 9-13, 2012
Where: Hynes Convention Center Boston, Massachusetts
Contact: Please click here to obtain a press pass for this event.

Press releases and all abstracts are available online at www.aasld.org.
Media Contact: Ann Haran 703/299-9766 aharan@aasld.org Press Room: November 10 – November 13, 2012 Hynes Convention Center, Room 208

"This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com."
SOURCE American Association for the Study of Liver Diseases (AASLD)

Read more here: http://www.sacbee.com/2012/11/02/4957094/six-late-breaking-abstracts-selected.html#storylink=cpy

Hepatitis C - Alcohol effects on liver diseases: good or bad buddy?

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AASLD and Advocacy: Sometimes it Takes Awhile

AASLD and Advocacy: Sometimes it Takes Awhile

By Lyle Dennis, Cavarocchi – Ruscio – Dennis Associates, Consultants to AASLD

It is axiomatic that the wheels of government turn slowly. Sometimes, we see that they do not turn at all! But when government acts and acts in the interest of your patients as result of AASLD’s efforts, it is important that you know about it. Recently, two examples have come across our desk (or more accurately our computer screen) that are worth mentioning.

The FDA and Acetaminophen

A couple of years ago, the three FDA advisory committees held a joint hearing to discuss the role of acetaminophen in liver toxicity. Acetaminophen is, of course, one of the safest drugs on the market when used appropriately, following label directions. However, sometimes people assume that more is better or they don’t realize that it is included in other pain-relieving drugs. In that way, patients can get into trouble and the trouble is usually directly felt in the liver.

The FDA considered multiple options for reducing the possibility of inadvertent overdose of acetaminophen. AASLD was an active participant in the process. Dr. Tim Davern testified on AASLD’s behalf; Dr. Will Lee was an expert advisor to the FDA. AASLD sought aggressive action from the FDA to reduce risk to patients.

While we certainly did not get all we asked for in the hearing, the FDA eventually did adopt some additional restrictions on acetaminophen. Among them was limiting its presence in prescriptions medicines to 325 mg or lower, the equivalent of a single regular strength OTC pill.

Last month, the FDA approved a new formulation for Vicodin® that contains 300 mg of acetaminophen – the lowest effective dose of the pain reliever in combination hydrocodone products. It is going on the market more than a year before the FDA deadline and revised packaging will communicate the new levels to doctors, pharmacists, and patients.

This is one step in addressing a significant and complicated problem, but it seems clear that AASLD’s experts like Drs. Davern and Lee played a significant role in moving this cause forward.

The Viral Hepatitis Action Plan

Regular readers know the sequence of events that led to the Department of Health and Human Services (HHS) adopting an action plan to address viral hepatitis in May 2011. First, an Institute of Medicine Report on the problem; then AASLD and the Trust for America’s Health combined to issue a blueprint for addressing this issue; then the Action Plan was issued by the Office of the Assistant Secretary for Health Dr. Howard Koh.

Recently, HHS issued the Interagency Implementation Progress Report – Year 1 and it is full of hopeful and helpful information. Implementation is proceeding apace in fifteen HHS agencies, as well as in the Federal Bureau of Prisons and the Department of Veterans Affairs

This report highlights the progress that has been made in the first year since the plan was adopted.

If you click on the link above and read the report, you will find a stunning level of cooperation among government agencies that have not always played nicely in the sandbox together. As you read it, you can be proud to know that AASLD was involved with creating this report, working on the ground floor with the Assistant Secretary for Health and the with the CDC to make it a reality.

These are just two recent examples among many where aggressive advocacy on the part of AASLD, its leadership, and its members has resulted in moving the proverbial needle on government action.  http://www.aasld.org/news/110112/Pages/default.aspx

Pretreatment Care Predicts Hepatitis C Outcomes

Pretreatment Care Predicts HCV Outcomes

By: MARY ANN MOON, Family Practice News Digital Network

Patients with hepatitis C infections are more likely to initiate appropriate antiviral therapy and achieve a sustained virologic response if they receive high quality health care, Dr. Fasiha Kanwal of the Michael E. DeBakey Veterans Affairs Medical Center, Houston, and her colleagues reported in the November issue of Clinical Gastroenterology and Hepatology.

In their study of nearly 35,000 adults with HCV, the odds of initiating antiviral therapy were threefold higher in patients who received optimal care from the moment HCV infection was diagnosed than in those who did not. And among patients who initiated antiviral therapy, the quality of care they received before that therapy even began strongly predicted whether they would complete antiviral therapy and achieve a sustained virologic response, the investigators said.

The study showed, however, that only 11% of patients received all of the appropriate initial care.

Process-of-care measures are frequently used to assess the quality of care for HCV, but until now no study has assessed whether these measures actually correlate with better outcomes. To address this issue, Dr. Kanwal and her associates "evaluated the relationship between adherence to a broad set of process-based measures in HCV and 3 subsequent HCV-specific endpoints: receipt of antiviral treatment, completion of antiviral treatment, and the clinical outcome associated with improved survival: sustained virologic response."

The investigators used data from the VA registry on HCV clinical care, which covers patient demographics, lab tests, pharmacy information, and data on inpatient and outpatient care for approximately 300,000 patients across the country. For this study, they included data on 34,749 adults.

The mean subject age was 53 years, and 97% were men. Approximately half the study population was white and 26% was black; ethnicity was not reported for the others.

The researchers assessed seven process-of-care measures: confirmation of HCV viremia, evaluation by HCV specialists, HCV genotype testing, liver biopsy for those found to have genotype 1 HCV, and the ruling out of liver diseases related to hepatitis B, autoimmunity, or iron overload.

They also assessed seven process-of-care measures related to the prevention and management of comorbid conditions: HIV testing; hepatitis A and B serology testing, hepatitis A and B vaccination if serology results proved negative; treatment of depression; and treatment of substance abuse disorder.

inally, they assessed six process-of-care measures related to monitoring of antiviral therapy’s effects: testing of viral load before antivirals were initiated and again at weeks 12, 24, and 48; reduction of ribavirin dose if anemia developed during treatment; and avoidance of prescribing growth-stimulating factors for leukopenia during antiviral therapy.

Overall, only 11% of the study subjects received all of the appropriate initial care, and 8% received all the appropriate care related to prevention and management of comorbid conditions. Moreover, of the study subjects who received antiviral therapy, just 37% received all the appropriate monitoring of treatment effects Dr. Kanwal and her associates said.

In patients who received optimal care before a definitive diagnosis was made, the odds of receiving antiviral therapy were 3.2 times higher than in patients who did not receive optimal care before diagnosis, they reported.

Similarly, patients who received optimal preventive and comorbid-condition care showed rates of antiviral therapy that were 36% higher than those of patients who received suboptimal preventive and comorbid-condition care.

The strong association between fulfillment of these process-of-care measures and appropriate antiviral therapy remained robust in a series of sensitivity analyses, which means it’s likely that meeting process-of-care goals directly leads to better HCV outcomes, Dr. Kanwal and her colleagues said.

The investigators could not, however, rule out the possibility that meeting these goals is simply a marker of more compliant patients, which in turn produces better outcomes.

The study findings imply that the effectiveness of the two new direct-acting antiviral agents that recently became available for HCV may hinge on the quality of care patients are receiving before they even start taking these drugs, rather than simply on the effectiveness of the drugs alone, Dr. Kanwal and her associates said.

This study was supported by the U.S. Department of Veterans Affairs Health Services Research and Development Service. No financial conflicts of interest were reported.

 Quality Measures Supported
Financial reimbursement in medicine has long been driven by volume rather than quality. This incentive structure is changing, and in the near future practitioners will experience increased scrutiny of the quality of care we provide.

Dr. Michael Volk

Quality can be divided into structure (having the proper equipment to clean endoscopes), process (testing for latent tuberculosis before beginning anti–tumor necrosis factor therapy), and outcomes (perforation rate during colonoscopy). The latter is, of course, the most important, but it is also the most difficult to measure because of low event rates and inadequate risk adjustment. Therefore, most quality measures are based on processes of care. For quality measurement to yield any true value to the patient, however, it is important that these processes are clearly linked to better patient outcomes.
Hepatitis C, which affects 1.3% of Americans, has recently been a target disease for measuring and improving quality of care. Dr. Kanwal and her colleagues found that patients receiving optimum process-related quality care were more likely to undergo antiviral therapy. Such patients also were more likely to complete treatment once started and to achieve sustained virologic response if treatment was completed. Since these findings persisted despite adjustment for numerous potential confounders such as comorbidities, it appears that higher quality of care (as measured by processes) may truly lead to better patient outcomes.

What does this mean for practitioners?

Particularly in the era of triple therapy, hepatitis C virus (HCV) infection cannot be managed like any other disease. Protocols and tracking systems need to be developed to ensure that quality measures are met. Many practices find it helpful to funnel HCV patients to a single person for case management, such as a nurse or midlevel provider. Hopefully, these efforts, in conjunction with newer antivirals, will soon eradicate hepatitis C altogether.

Michael Volk, M.D., is assistant professor of hepatology at the University of Michigan, Ann Arbor.

http://www.familypracticenews.com/news/infectious-diseases/single-article/pretreatment-care-predicts-hcv-outcomes/32eb66f77e591177db173cd150e5b102.html

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)

Idenix Reports Financial Results and HCV Program Update

Idenix Pharmaceuticals Reports Third Quarter and Nine Month 2012 Financial Results and HCV Program Update

CAMBRIDGE, Mass., Nov. 1, 2012 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today reported unaudited financial results for the third quarter and nine months ended September 30, 2012 and provided an update of its hepatitis C virus (HCV) development programs.

 

HCV Pipeline and Third Quarter Business Review
IDX719, an NS5A inhibitor

• The Company previously reported early clinical results demonstrating a favorable safety profile and potent pan-genotypic activity for IDX719. Idenix anticipates that a phase II clinical trial evaluating IDX719 in combination therapy will begin in the first half of 2013.

Nucleotide polymerase inhibitor program

• In August 2012, the U.S. Food and Drug Administration (FDA) placed IDX184 on partial clinical hold due to serious cardiac--related adverse events seen with a competitor's nucleotide polymerase inhibitor, BMS-986094 (formerly INX-189). Idenix has obtained cardiac safety measurements from the ongoing phase IIb study of IDX184 in combination with pegylated interferon and ribavirin and has found no evidence of severe cardiac findings to date. Idenix is reviewing additional preclinical and clinical data and conducting further testing . The Company anticipates submitting the complete response package to the FDA by year-end.
• In July 2012, Idenix submitted an investigational new drug (IND) application for IDX19368, a 2'methyl guanosine nucleotide inhibitor. In August 2012, FDA placed IDX19368 on clinical hold due to serious cardiac-related adverse events seen with BMS-986094 and has requested additional toxicology and metabolic preclinical studies for IDX19368 prior to permitting the initiation of clinical studies.
• As part of the ongoing extensive nucleotide discovery effort, the Company is exploring a diverse spectrum of nucleotides with novel bases, prodrugs and sugar moieties. IND-enabling studies have begun for a new nucleotide prodrug and an IND is expected to be filed in 2013.

"We are working diligently to assemble all of the data requested by the FDA regarding IDX184, and we expect to receive a response from the FDA in early 2013," said Ron Renaud, Idenix's President and Chief Executive Officer. "We also are excited about IDX719, a potentially best-in-class pan-genotypic NS5A inhibitor, and look forward to moving it into phase II clinical development in the near term. Additionally, in 2013 we expect to see the results of our robust discovery efforts focused on next-generation nucleotide inhibitors, with the objective of filing at least one IND next year."
Renaud continued, "Our goal remains to develop an all-oral pan-genotypic regimen that will play a significant role in future HCV treatments. With a strong cash position and the restructured Novartis collaboration, we are able to maximize opportunities for advancing our programs in order to achieve that goal."

Upcoming Meeting
The 63^rd Annual Meeting for the American Association for the Study of Liver Diseases (AASLD) will take place in Boston from November 9 -- November 13, 2012.

• A poster titled "IDX719, HCV NS5A Inhibitor, Demonstrates Pan-Genotypic Activity after Three Days of Monotherapy in Genotype 1, 2, 3 or 4 HCV-Infected Subjects," by D. Mayers, et al, will be presented on November 13 at 8:00 am ET.
• A poster titled "High Rates of Rapid Virologic Response (RVR) and Complete Early Virologic Response (cEVR) with IDX184, Pegylated Interferon and Ribavirin in Genotype 1 HCV-Infected Subjects: Interim Results," by E. Lawitz, et al, will be presented on November 13, 2012 at 8:00 am ET.

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

Vertex Enters Agreement with GlaxoSmithKline for Phase 2 All-Oral Study of VX-135 and GSK2336805 for the Treatment of Hepatitis

November 1, 2012

-Companies to evaluate two-drug combination of Vertex's investigational nucleotide analogue VX-135 and GSK's investigational NS5A inhibitor GSK2336805-

 

-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 it has entered into a non-exclusive agreement with GlaxoSmithKline (GSK) 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 GSK's NS5A inhibitor GSK2336805. Vertex and GSK plan to initiate the study in early 2013, pending discussions with regulatory authorities. The study is expected to evaluate safety, tolerability and viral cure rates using a 12-week combination of VX-135 and GSK2336805. The companies will jointly fund costs associated with the study. 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. GSK2336805 is an investigational NS5A replication complex inhibitor being developed by GSK for the treatment of hepatitis C.

  

"This agreement underscores our broad commitment to develop all-oral treatment regimens for people with hepatitis C using medicines within our own pipeline and by working in collaboration with other companies like GSK who share our commitment to further improve treatment of this disease," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "We are focused on the development of new all-oral treatments for hepatitis C that have the potential to provide a high cure rate with only 12 weeks of treatment, and we look forward to the start of this study with GSK."
  
Clinical Development Plans
The Phase 2 proof-of-concept study is expected to begin in early 2013, pending discussions with regulatory authorities, and will enroll people who have chronic non-cirrhotic genotype 1 hepatitis C and have not previously been treated (treatment-naïve). The study will be conducted in the U.S. by Vertex, and costs associated with the study will be split 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 of treatment) of multiple 12-week combination regimens of VX-135 and GSK2336805, with and without ribavirin. Additional information on the Phase 2 study will be provided upon initiation of the study. Further clinical development activities beyond the Phase 2 proof-of-concept study are not covered as part of this agreement.
  
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 of 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 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.
  
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 a Phase 2 study evaluating the combination of VX-135 and GSK2336805 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
Kelly Lewis, 617-444-7530
Source: Vertex Pharmaceuticals Incorporated

News Provided by Acquire Media

http://investors.vrtx.com/releases.cfm?hdr02=press