Merck’s Investigational Hepatitis C Treatment Regimen MK-5172/MK-8742 Shows Robust Anti-HCV Activity in HIV/HCV Co-Infected Patients with HCV Genotype 1 Infection

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Wednesday, March 5, 2014 4:15 pm EST

Public Company Information:

"We are encouraged by the potential of MK-5172/MK-8742 for the treatment of people living with HIV/HCV co-infection, where there remains a need for additional therapeutic options"

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced new data from HIV/HCV co-infected patients in the ongoing C-WORTHY Study, a Phase 2 clinical trial evaluating the efficacy and safety of Merck's 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. In these co-infected patients, the administration of MK-5172/MK-8742 for 12 weeks resulted in robust HCV suppression, and a safety profile consistent with that observed for patients infected with HCV Genotype 1 infection (GT1) alone.

At 12 weeks, 100 percent (29/29) of co-infected patients who received MK-5172/MK-8742 and ribavirin (RBV), and 90 percent (26/29) of co-infected patients who received MK-5172/MK-8742 alone had HCV RNA levels of less than 25 IU/mL, versus 100 percent (13/13) in patients with HCV alone treated with MK-5172/8742. The data were presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI).

We are encouraged by the potential of MK-5172/MK-8742 for the treatment of people living with HIV/HCV co-infection, where there remains a need for additional therapeutic options,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories.

About the MK-5172/MK-8742 Data Presented at CROI

After 4 weeks of treatment, all co-infected patients showed a reduction in HCV RNA levels to below 25 IU/mL with or without RBV administration. HCV kinetics over the first 4 weeks of therapy were similar in patients with or without HIV co-infection.

Virologic Response: Intent-to-Treat Population

 

 

 

 

 

 

 

 

 

# Patients with HCV RNA <25 IU/mL / total # of patients (%)

Treatment Week
(TW)

 

 

 

HIV/HCV Co-
infected MK-
5712+MK-8742 +
RBV, N= 29

 

 

 

HIV/HCV Co-
infected MK-
5712*+MK-8742,
N= 30

 

 

 

HCV Mono-
infected MK-
5172+MK-8742 +
RBV, N= 52

 

 

 

HCV Mono-
infected MK-
5172+MK-8742,
N= 13

TW2

 

 

 

26/29 (90%)

 

 

 

23/30 (77%)

 

 

 

47/52 (90%)

 

 

 

12/13 (92%)

TW4

 

 

 

29/29 (100%)

 

 

 

30/30 (100%)

 

 

 

50/52 (96%)

 

 

 

13/13 (100%)

TW8

 

 

 

29/29 (100%)

 

 

 

27/30 (90%)

 

 

 

49/52 (94%)

 

 

 

13/13 (100%)

TW12

 

 

 

29/29 (100%)

 

 

 

26/29 (90%)*

 

 

 

49/52 (94%)

 

 

 

13/13 (100%)

*One HIV/HCV co-infected patient had not yet reached TW12; HIV/HCV co-infected (RBV-free) arm: 1 lost to follow-up (HCV RNA undetectable at the last visit on record); 2 breakthroughs with low blood levels of MK-5172 and/or MK-8742; HCV mono-infected (RBV-containing) arm: 3 early discontinuations (day 3 [detectable at the last visit] and days 22 and 35 [undetectable at the last visit]).

There were three treatment failures in the HIV/HCV co-infected study arms; one subject completed the treatment regimen but was lost to follow-up (HCV RNA undetectable at the last visit on record); and two co-infected subjects with low pharmacokinetic levels of MK-5172 and/or MK-8742 experienced virologic breakthrough at the 8 week time point (both cases with low blood levels of MK-5172 and/or MK-8742).

The most common adverse events observed in this cohort were fatigue (7%) and headache (8%). The incidence of these adverse events was not increased in patients with HIV. No co-infected patients discontinued due to either an adverse event or study medication intolerance.

About HIV/HCV Co-Infection

Globally, approximately seven million patients are co-infected with HIV and HCV. HCV is the leading cause of morbidity and mortality among those living with HIV-1, and compared to the general population, the overall prevalence of HCV infection is higher among those infected with HIV-1. Furthermore, HIV/HCV co-infected patients have a three times higher rate of progression to cirrhosis and a six times higher risk of hepatic decompression than HCV patients infected with HCV alone, underscoring the need for new therapeutic options for this patient population.

About the C-WORTHY Clinical Trial

C-WORTHY is a randomized, dose-responsive, parallel-group, multiple-site, open-label trial comparing different patient populations exposed to different durations of treatment of MK-5172 (100 mg QD) in combination with MK-8742 (50 mg QD) with or without RBV in patients with chronic HCV infection. A total of 450 patients with HCV GT1 and HCV RNA levels of ≥10,000 IU/mL have been enrolled in C-WORTHY and randomized across 16 arms to examine difficult-to-treat subpopulations.

The primary objective of C-WORTHY is to evaluate the safety and efficacy of MK-5172 in combination with MK-8742 with or without RBV as assessed by the proportion of patients achieving sustained virologic response at 12 weeks (SVR12) in treatment-naïve patients and more complex patient groups including prior peginterferon alfa and ribavirin treatment failures, cirrhotic patients and co-infected patients. The aim of the HIV/HCV co-infected arms is to compare on-treatment HCV RNA responses (defined as proportion of patients with HCV RNA <25 IU/mL) in GT1 HIV/HCV co-infected patients treated with MK-5712/MK-8742 with or without RBV with those in mono-infected patients.

In the HIV/HCV co-infection arms, 59 treatment-naïve, non-cirrhotic, GT1 HIV/HCV co-infected patients on a stable antiretroviral regimen (raltegravir + tenofovir or abacavir with either 3TC or FTC) were examined. These subjects were randomized at a 1:1 ratio to receive 12 weeks of MK-5172 (100 mg QD) administered concomitantly with MK-8742 (50 mg QD), with or without twice daily (BID) RBV.

Additional data from Merck’s Phase 2 program for MK-5172/MK-8742 will be presented at the 49th Annual Meeting of the European Association of the Study of the Liver, April 9-13 in London. Details on the C-WORTHY Study, as well as additional Phase 2 trials for MK-5172 and MK-8742, can be viewed on www.merck.com/clinical-trials.

In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to MK-5172/MK-8742 for treatment of chronic HCV infection.

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 , 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).

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