UPDATE 2-Merck says hepatitis C drugs to lose breakthrough status
By Ransdell Pierson
Feb 4 (Reuters) - Merck & Co on Wednesday said the U.S. Food and Drug Administration intends to rescind its "breakthrough therapy" designation for the company's experimental combination treatment for hepatitis C because of other recently approved treatments.
Merck, in its fourth-quarter earnings report, said it plans to discuss the matter with the FDA, and still expects to seek U.S. approval for the treatment in the first half of 2015. It consists of a protease inhibitor called MK-5172 and a so-called NS5A inhibitor called MK-8742 that together had received the "breakthrough therapy" designation from the FDA.
Shares of the second-biggest U.S. drugmaker slumped 2.3 percent in premarket trading.
The setback for Merck's treatment follows recent approvals of costly oral treatments for the liver disease from Gilead Sciences Inc and AbbVie that have wiped out all signs of the virus in more than 90 percent of patients after eight or 12 weeks.
In the face of such potent rival medicines, Merck in June announced it would ramp up its involvement in the lucrative hepatitis C market by buying Idenix Pharmaceuticals Inc for $3.85 billion and combining the two companies' most promising drugs to produce a faster, more effective cure for hepatitis C. It agreed to pay $24.50 per share, more than three times Idenix's share price before the deal was made public.
Idenix had three drugs in development to treat hepatitis C, most notably a pill in early-stage trials called IDX21437, which Merck has renamed MK-3682. Like Gilead's Sovaldi, it is a nucleotide inhibitor - or "nuc" - that blocks a protein needed by the hepatitis C virus to replicate.
Merck is conducting a mid-stage trial to study combinations of MK-3682 and MK-5172 (grazoprevir) with either MK-8742 (elbasivir) or another drug called MK-8408. It hopes to begin larger late-stage trials later this year.
"We do not see this affecting the development of the combo," said JPMorgan analyst Chris Schott, referring to the potential loss of the special "breakthrough" designation, which provides a gloss of specialness to drugs and can speed up an FDA review.
Gilead introduced Sovaldi in late 2013 at a cost of $1,000 a pill, and reported fourth-quarter sales of $1.73 billion for the drug. Gilead later introduced Harvoni, a new pill combining Sovaldi with another treatment, and it captured sales of $2.11 billion in the quarter.
After AbbVie launched its Viekira Pak treatment late last year, it and Gilead have fought for market share by offering rebates to group payers.
Gilead estimated that 141,000 Americans have been started on one of its hepatitis C products so far, and it expects 250,000 to be treated this year. As many as 3.2 million people in the United States are estimated to be infected with the hepatitis C virus, which can lead to severe liver disease.
STRONG DOLLAR HURTS
Merck on Wednesday reported slightly disappointing fourth-quarter sales and predicted 2015 earnings below analyst forecasts, citing the negative impact of the stronger dollar, as most of its U.S. rivals have done in making their own cautious forecasts.
Merck said it expects full-year 2015 earnings of $3.32 to $3.47 per share, excluding special items, with foreign exchange factors crimping earnings by 27 cents per share. Wall Street had predicted $3.49 per share.
The company said it earned $7.32 billion, or $2.54 per share, in the quarter. That compared with $781 million, or 26 cents per share, in the year-earlier period.
Excluding special items, the company earned 87 cents per share. Analysts, on average, expected 85 cents per share, according to Thomson Reuters I/B/E/S.
Company revenue fell 7 percent to $10.48 billion, trailing Wall Street expectations of $10.5 billion, held back by lower sales of its Remicade arthritis drug, now facing competition abroad from cheaper generic drugs. Sales would have fallen 4 percent if not for the stronger dollar, which lowers the value of sales abroad, when converted back into U.S. currency. (Reporting by Ransdell Pierson; Editing by W Simon and Paul Simao)
Showing posts with label MK-5172/MK-8742. Show all posts
Showing posts with label MK-5172/MK-8742. Show all posts
Wednesday, February 4, 2015
Friday, April 11, 2014
EASL - Merck’s MK-5172/MK-8742 Demonstrates Antiviral Activity in Hard-to-Cure Patients
Also See -EASL-Merck reports mid-stage data for MK-5172 and MK-8742, all-oral hepatitis C regimen
Merck’s Investigational Chronic Hepatitis C Combination Therapy MK-5172/MK-8742 Demonstrates Antiviral Activity in Hard-to-Cure Patients with HCV Genotype 1 Infection
April 11
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced interim results from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of an all-oral, once-daily regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). Interim analysis of hard-to-cure1 patients administered MK-5172/MK-8742 with and without ribavirin (RBV) for 12 or 18 weeks showed sustained viral response2 (SVR), 4 to 8 weeks after the completion of therapy (SVR4/8):
.
“There is still a need for further options for the most difficult-to-cure patients, including those with cirrhosis and HCV/HIV co-infection,” said Dr. Eric Lawitz, MD, vice president, Scientific and Research Development, The Texas Liver Institute, and clinical professor of medicine, University of Texas Health Science Center in San Antonio. “These findings provide additional clinical evidence regarding the potential of MK-5172/MK-8742 in treating a broad spectrum of HCV patients.”
.
C-WORTHy Study Design
C-WORTHy is a randomized, dose-responsive, parallel-group, multiple-site, double-blind clinical trial comparing different patient populations exposed to different durations of treatment of MK-5172 (100 mg once daily) in combination with MK-8742 (50 mg once daily) with or without RBV in subjects with chronic HCV infection. A total of 471 patients with chronic HCV GT1 and HCV RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy and randomized across 16 arms. These results examine hard-to-cure subpopulations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV), prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV) and patients with HIV/HCV co-infection (12-week arms).
.
Key Findings for MK-5172/MK-8742
Viral suppression (HCV RNA levels less than 25 IU/mL) was demonstrated for treatment-naïve patients with cirrhosis, prior-null responder patients with and without cirrhosis and HIV/HCV co-infected patients by Treatment Week (TW)12. These levels were maintained at rates between 90 and 100 percent across patient subgroups through the completion of dosing and at the four-week treatment follow-up time point (FU4).
The most common adverse events observed among treatment-naïve patients with cirrhosis and prior-null responder patients with and without cirrhosis were fatigue (23% and 28%, respectively), headache (24% and 24%, respectively), and asthenia (8% and 19%, respectively). The most common adverse events observed among HIV co-infected patients were headache (8%), asthenia (8%), fatigue (7%), and sleep disorder (7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities observed in routine laboratory analysis of hematologic markers.
.
About Merck’s Phase 3 HCV Program: C-EDGE
Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be found at www.clinicaltrials.gov.
.
Merck’s Commitment to HCV
For more than 25 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HCV worldwide.
Source
Merck’s Investigational Chronic Hepatitis C Combination Therapy MK-5172/MK-8742 Demonstrates Antiviral Activity in Hard-to-Cure Patients with HCV Genotype 1 Infection
April 11
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced interim results from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of an all-oral, once-daily regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). Interim analysis of hard-to-cure1 patients administered MK-5172/MK-8742 with and without ribavirin (RBV) for 12 or 18 weeks showed sustained viral response2 (SVR), 4 to 8 weeks after the completion of therapy (SVR4/8):
.
- HCV GT1 infected, treatment-naïve cirrhotic patients, MK-5172/MK-8742 treated - 97 percent (28/29 and 29/30) for 12 and 18 weeks, and MK-5172/MK-8742 plus RBV - 90 percent (28/31) and 97 percent (30/31) for 12 and 18 weeks, respectively.
- HCV GT1 infected prior-null responder patients (with or without cirrhosis), MK-5172/MK-8742 treated - 91 percent (30/33) and 97 percent (29/30) for 12 and 18 weeks, respectively, and MK-5172/MK-8742 plus RBV treated 94 percent (30/32) and 100 percent (32/32) for the 12 and 18 weeks, respectively.
- Treatment-naïve, non-cirrhotic patients with HCV/HIV co-infection, MK-5172/MK-8742 treated for 12 weeks - 90 percent (26/29) and MK-5172/MK-8742 plus RBV for 12 weeks 97 percent (28/29).
“There is still a need for further options for the most difficult-to-cure patients, including those with cirrhosis and HCV/HIV co-infection,” said Dr. Eric Lawitz, MD, vice president, Scientific and Research Development, The Texas Liver Institute, and clinical professor of medicine, University of Texas Health Science Center in San Antonio. “These findings provide additional clinical evidence regarding the potential of MK-5172/MK-8742 in treating a broad spectrum of HCV patients.”
.
C-WORTHy Study Design
C-WORTHy is a randomized, dose-responsive, parallel-group, multiple-site, double-blind clinical trial comparing different patient populations exposed to different durations of treatment of MK-5172 (100 mg once daily) in combination with MK-8742 (50 mg once daily) with or without RBV in subjects with chronic HCV infection. A total of 471 patients with chronic HCV GT1 and HCV RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy and randomized across 16 arms. These results examine hard-to-cure subpopulations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV), prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV) and patients with HIV/HCV co-infection (12-week arms).
.
Key Findings for MK-5172/MK-8742
Viral suppression (HCV RNA levels less than 25 IU/mL) was demonstrated for treatment-naïve patients with cirrhosis, prior-null responder patients with and without cirrhosis and HIV/HCV co-infected patients by Treatment Week (TW)12. These levels were maintained at rates between 90 and 100 percent across patient subgroups through the completion of dosing and at the four-week treatment follow-up time point (FU4).
.
Table 1
|
|||||||||
Interim Analysis of the C-WORTHy Trial: Treatment-Naïve,
Cirrhotic Patients with HCV
GT1 Infection (Intention-to-Treat Analysis (ITT), Excluding
Patients Yet to Reach FU4)
|
|||||||||
| Parameter | MK-5172 + MK-8742 + RBV (12 Weeks) (N = 31) |
MK-5172 + MK-8742 (NO RBV) (12 Weeks) (N = 29) |
MK-5172 + MK-8742 + RBV (18 Weeks) (N = 32) |
MK-5172 + MK-8742 (NO RBV) (18 weeks) (N = 31) |
|||||
SVR4/8, % (n/m†)
|
90% (28/31) | 97% (28/29) | 97% (30/31) | 97% (29/30) | |||||
| No SVR, % (n) | |||||||||
| Breakthrough | 3% (1) | 0% (0) | 0% (0) | 0% (0) | |||||
| Relapse | 7% (2) | 3% (1) | 0% (0) | 3% (1) | |||||
| Non-virologic Discontinuation | 0% (0) | 0% (0) | 3% (1) | 0% (0) | |||||
† m = patients who have reached the FU4 visits (all patients in
the 12-week arms, and 61/63 patients in the 18-week arms have
reached FU4).
|
|||||||||
,
Table 2
|
|||||||||
Interim Analysis of the C-WORTHy Trial: Prior Null
Responders (~50% Cirrhotics),
Cirrhotic Patients with HCV GT1 Infection (ITT, Excluding
Patients Yet to Reach FU4)
|
|||||||||
| Parameter | MK-5172 + MK-8742 + RBV (12 Weeks) (N = 32) |
MK-5172 + MK-8742 (NO RBV) (12 Weeks) (N = 33) |
MK-5172 + MK-8742 +
RBV (18 Weeks) (N = 33) |
MK-5172 + MK-8742 (NO RBV) (18 weeks) (N = 32) |
|||||
SVR4/8, % (n/m†)
|
94% (30/32) | 91% (30/33) | 100% (32/32) | 97% (29/30) | |||||
| No SVR, % (n) | |||||||||
| Breakthrough | 0% (0) | 0% (0) | 0% (0) | 3% (1) | |||||
| Relapse | 0% (0) | 9% (3) | 0% (0) | 0% (0) | |||||
| Non-virologic Discontinuation | 6% (2) | 0% (0) | 0% (0) | 0% (0) | |||||
| † m = patients who have reached the FU4 visits (all patients in the 12-week arms, and 62/65 patients in the 18-week arms have reached FU4). | |||||||||
.
Table 3
|
|||||
Interim Analysis of the C-WORTHy Trial:Treatment-Naïve
Non-Cirrhotic HCV GT1-Infected
Patients with HIV Co-Infection (ITT, Excluding Patients Yet to Reach FU4) |
|||||
| Parameter | MK-5172 + MK-8742 + RBV (12 Weeks) (N = 29) |
MK-5172 + MK-8742 (NO RBV) (12 Weeks) (N = 30) |
|||
SVR4/8, % (n/m†)
|
97% (28/29) | 90% (26/29) | |||
| No SVR, % (n) | |||||
| Breakthrough | 0% (0) | 7% (2) | |||
| Relapse | 3% (1) | 0% (0) | |||
| Non-virologic Discontinuation | 0% (0) | 3% (1) | |||
| † m = patients who have reached the FU4 visits (only one patient in the RBV-free arm has not yet reached FU4). | |||||
The most common adverse events observed among treatment-naïve patients with cirrhosis and prior-null responder patients with and without cirrhosis were fatigue (23% and 28%, respectively), headache (24% and 24%, respectively), and asthenia (8% and 19%, respectively). The most common adverse events observed among HIV co-infected patients were headache (8%), asthenia (8%), fatigue (7%), and sleep disorder (7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities observed in routine laboratory analysis of hematologic markers.
.
About Merck’s Phase 3 HCV Program: C-EDGE
Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be found at www.clinicaltrials.gov.
.
Merck’s Commitment to HCV
For more than 25 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HCV worldwide.
Source
Thursday, April 10, 2014
EASL-Merck reports mid-stage data for MK-5172 and MK-8742, all-oral hepatitis C regimen
Investment Commentary
UPDATED: Watch out Gilead, Merck is mounting a hep C combo comeback
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced additional data from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of a once-daily, all-oral regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). In an interim analysis of treatment-naïve, non-cirrhotic patients administered a 12-week regimen of MK-5172/MK-8742, with and without ribavirin (RBV), a sustained viral response1 (SVR) was observed in 98 percent (42/43) of patients administered MK-5172/MK-8742 alone and 94 percent (75/80) in those administered MK-5172/MK-8742 plus RBV.
These data were presented, along with data on an 8-week regimen, at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), also known as The International Liver Congress™ 2014, in London, UK.
“These Phase 2 results add to growing evidence for the potential efficacy of MK-5172 and MK-8742 for treatment of chronic HCV infection,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories. “These findings are integral to advancing our research of these investigational candidates into C-EDGE, the Phase 3 clinical program that will seek to more broadly evaluate the potential of MK-5172/MK-8742 in diverse patient populations.”
C-WORTHy Study Design
C-WORTHy is a two-part, parallel-group, randomized (within group) clinical trial evaluating a range of subpopulations of patients with HCV GT1 infection. The study evaluated different treatment durations of MK-5172 (100 mg once daily) plus MK-8742 (50 mg once daily), with or without RBV. A total of 471 patients with HCV GT1 RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy across 16 arms.
Key Findings for MK-5172/MK-8742
The interim results presented were from treatment-naïve, non-cirrhotic patients who received one of 3 regimens: A) MK-5172/MK-8742 + RBV for 8 weeks (N=30), B) MK-5172/MK-8742 + RBV for 12 weeks (N=85), and C) MK-5172/MK-8742 (without RBV) for 12 weeks (N=44), (see table 1).
Table 1 – Interim Results from the C-WORTHy Trial Showing Treatment-Naïve, Non-Cirrhotic Patients with HCV GT1 Infection (Intention-to-Treat (ITT) Analysis)
Among the five patients who relapsed in the eight-week regimen arm of PN035B, two patients had very low MK-5172 and MK-8742 levels during the course of therapy. The relationship between this finding and the relapse is being investigated.
The most common adverse events recorded in the RBV and RBV-free treatment groups, respectively, were fatigue (32%, 23%), headache (20%, 33%), nausea (21%, 16%), diarrhea (13%, 9%) and insomnia (13%, 7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities detected in routine laboratory analysis of hematologic markers.
PN038 Study Design and Findings
Additionally, new data from PN038, a Phase 2 dose-ranging clinical trial evaluating MK-5172 once-daily with peginterferon alfa-2b and ribavirin (PR, weekly), were presented, evaluating SVR24 in treatment-naïve, non-cirrhotic patients with GT1 infection. PN038 is a Phase 2 clinical trial investigating the efficacy and safety of MK-5172 doses (25 mg, 50 mg, and 100 mg) once-daily with PR over a 12-week treatment cycle in GT1 treatment-naïve, non-cirrhotic patients (n=87). The analysis presented was ITT, in which all patients who did not achieve SVR (including those who dropped out for non-virologic reasons), were recorded as failures.
MK-5172 at doses of 50 mg and 100 mg with PR for 12 weeks of treatment achieved SVR24 rates of 75.0 percent (21/28) and 83.3 percent (25/30), respectively, supporting use of MK-5172 below 100 mg dose (see table 2).
Table 2: PN038 Virologic Responses – (ITT Analysis)
*Treatment week
The most common recorded adverse experiences recorded across all treatment arms were: fatigue (61%), headache (46%), nausea (43%), and decreased appetite (43%). These adverse experiences did not appear to be dose-related.
One patient discontinued therapy after seven days of dosing with MK-5172 100 mg, plus PR and experienced muscle inflammation (creatine kinase >5x upper limits of normal [ULN]), elevated transaminases to >3x ULN, and total bilirubin >2x ULN, associated with a positive toxicology screen for ethanol. There were no other clinically significant transaminase elevations recorded in this study.
About Merck’s Phase 3 HCV Program: C-EDGE
Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be found at www.clinicaltrials.gov.
Merck’s Commitment to HCV
For more than 25 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HCV worldwide.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
Merck Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
1 Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, 12, or 24 weeks after the completion of therapy
UPDATED: Watch out Gilead, Merck is mounting a hep C combo comeback
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced additional data from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of a once-daily, all-oral regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). In an interim analysis of treatment-naïve, non-cirrhotic patients administered a 12-week regimen of MK-5172/MK-8742, with and without ribavirin (RBV), a sustained viral response1 (SVR) was observed in 98 percent (42/43) of patients administered MK-5172/MK-8742 alone and 94 percent (75/80) in those administered MK-5172/MK-8742 plus RBV.
These data were presented, along with data on an 8-week regimen, at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), also known as The International Liver Congress™ 2014, in London, UK.
“These Phase 2 results add to growing evidence for the potential efficacy of MK-5172 and MK-8742 for treatment of chronic HCV infection,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories. “These findings are integral to advancing our research of these investigational candidates into C-EDGE, the Phase 3 clinical program that will seek to more broadly evaluate the potential of MK-5172/MK-8742 in diverse patient populations.”
C-WORTHy Study Design
C-WORTHy is a two-part, parallel-group, randomized (within group) clinical trial evaluating a range of subpopulations of patients with HCV GT1 infection. The study evaluated different treatment durations of MK-5172 (100 mg once daily) plus MK-8742 (50 mg once daily), with or without RBV. A total of 471 patients with HCV GT1 RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy across 16 arms.
Key Findings for MK-5172/MK-8742
The interim results presented were from treatment-naïve, non-cirrhotic patients who received one of 3 regimens: A) MK-5172/MK-8742 + RBV for 8 weeks (N=30), B) MK-5172/MK-8742 + RBV for 12 weeks (N=85), and C) MK-5172/MK-8742 (without RBV) for 12 weeks (N=44), (see table 1).
Table 1 – Interim Results from the C-WORTHy Trial Showing Treatment-Naïve, Non-Cirrhotic Patients with HCV GT1 Infection (Intention-to-Treat (ITT) Analysis)
| Parameter | MK-5172 + MK-8742 (NO RBV) (12 Weeks) (N =44) |
MK-5172 + MK-8742 + RBV (12 Weeks) (N = 85) |
MK-5172 + MK-8742 + RBV (8 Weeks) (N =30) |
||||||
| SVR4-24†, % (n) | 98% (43) | 94% (80) | 83% (25) | ||||||
| No SVR, % (n) | |||||||||
| Breakthrough | 0 | 1% (1) | 0 | ||||||
| Relapse | 2% (1) | 1% (1) | 17% (5) | ||||||
| Non-virologic Discontinuation | 0 | 4% (3) | 0 | ||||||
| By Sub-genotype | |||||||||
| GT1a | 97% (29) | 94% (49) | 83% (25) | ||||||
| GT1b§ | 100% (14) | 94% (31) | -- | ||||||
† Part A: 100% of patients completed Follow-up week (FU)24; Part
B: 8 week arm: 93% have completed FU8; 12 week arm: 100% of
patients have completed FU4; 2 patients (Part A) and 1 patient
(Part B) discontinued early and are counted as failures.
§ Two patients with GT1 (non-a, non-b) were enrolled; these are
analyzed with GT1b.
|
|||||||||
Among the five patients who relapsed in the eight-week regimen arm of PN035B, two patients had very low MK-5172 and MK-8742 levels during the course of therapy. The relationship between this finding and the relapse is being investigated.
The most common adverse events recorded in the RBV and RBV-free treatment groups, respectively, were fatigue (32%, 23%), headache (20%, 33%), nausea (21%, 16%), diarrhea (13%, 9%) and insomnia (13%, 7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities detected in routine laboratory analysis of hematologic markers.
PN038 Study Design and Findings
Additionally, new data from PN038, a Phase 2 dose-ranging clinical trial evaluating MK-5172 once-daily with peginterferon alfa-2b and ribavirin (PR, weekly), were presented, evaluating SVR24 in treatment-naïve, non-cirrhotic patients with GT1 infection. PN038 is a Phase 2 clinical trial investigating the efficacy and safety of MK-5172 doses (25 mg, 50 mg, and 100 mg) once-daily with PR over a 12-week treatment cycle in GT1 treatment-naïve, non-cirrhotic patients (n=87). The analysis presented was ITT, in which all patients who did not achieve SVR (including those who dropped out for non-virologic reasons), were recorded as failures.
MK-5172 at doses of 50 mg and 100 mg with PR for 12 weeks of treatment achieved SVR24 rates of 75.0 percent (21/28) and 83.3 percent (25/30), respectively, supporting use of MK-5172 below 100 mg dose (see table 2).
Table 2: PN038 Virologic Responses – (ITT Analysis)
| Patients with HCV RNA <25 IU/mL / total # of patients (%) | ||||||||||||
| MK-5172 25 mg with PR (N=29) |
MK-5172 50 mg with PR (N=28) |
MK-5172 100 mg with PR (N=30) |
||||||||||
| TW*4 | 93.1% (27/29) | 96.4% (27/28) | 100.0% (30/30) | |||||||||
| TW12 | 93.1% (27/29) | 96.4% (27/28) | 96.7% (29/30) | |||||||||
| SVR12 | 48.3% (14/29) | 75.0% (21/28) | 86.7% (26/30) | |||||||||
| SVR24 | 48.3% (14/29) | 75.0% (21/28) | 83.3% (25/30) | |||||||||
*Treatment week
The most common recorded adverse experiences recorded across all treatment arms were: fatigue (61%), headache (46%), nausea (43%), and decreased appetite (43%). These adverse experiences did not appear to be dose-related.
One patient discontinued therapy after seven days of dosing with MK-5172 100 mg, plus PR and experienced muscle inflammation (creatine kinase >5x upper limits of normal [ULN]), elevated transaminases to >3x ULN, and total bilirubin >2x ULN, associated with a positive toxicology screen for ethanol. There were no other clinically significant transaminase elevations recorded in this study.
About Merck’s Phase 3 HCV Program: C-EDGE
Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection). Study information can be found at www.clinicaltrials.gov.
Merck’s Commitment to HCV
For more than 25 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HCV worldwide.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
Merck Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
1 Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, 12, or 24 weeks after the completion of therapy
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