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):
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“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.”
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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).
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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.
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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.
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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):
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- 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).
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Table 1
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|||||||||
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).
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|||||||||
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Table 2
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|||||||||
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). | |||||||||
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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
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