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-na�ve, 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-na�ve, 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)
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.
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
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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 (News - Alert)) 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