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
Merck may be late to the blockbuster party with its new hepatitis C drugs, but the pharma giant is moving fast with a top contender boasting high cure rates. Merck ($MRK) unveiled interim Phase II results for an oral combination of MK-5172, its NS3/4A protease inhibitor, and MK-8742, an NS5A, among patients with chronic HCV genotype 1 infection. After 12 weeks of therapy 42 of 43 patients--98%--demonstrated a sustained viral response. The combination plus ribavirin hit a 94% cure rate. And the drugs did it without any injections of interferon, which is widely hated by patients.

Merck hepatitis C drugs shine in easier to treat patients: study
By Bill Berkrot
Thu Apr 10, 2014 1:17am EDT 
Reuters - A two-drug combination being tested by Merck & Co to treat hepatitis C cured 98 percent of previously untreated patients without cirrhosis in a midstage clinical trial, providing the latest evidence that the U.S. drugmaker will be highly competitive in the fast evolving field.

Results of the study called C-Worthy were presented on Thursday at the annual meeting of the European Association for the Study of the Liver (EASL) in London. Researchers are due on Friday to present results of how the Merck pills fared in more difficult to treat patients, such as those who failed to be helped by prior treatments and those with more advanced liver disease.

In the arm of the Phase II study presented on Thursday, 43 of 44 patients treated with 100 milligrams of MK-5172 and 50 mg of MK-8742 once a day for 12 weeks achieved sustained virologic response (SVR), which is considered cured. One patient relapsed, researchers said.

Those who have no detectable levels of the hepatitis C virus in their blood 12 weeks after completing the 12 weeks of treatment are deemed to have achieved SVR.

Current standard treatments take 24 or 48 weeks, cure about 75 percent of patients and involve miserable side effects that have led thousands of patients to put off treatment and wait for highly touted new drugs to become available.

The study also included results of patients treated with the two Merck drugs plus the older drug ribavirin for both 12 weeks and eight weeks. But all eyes will be on the ribavirin-free results as several companies race to produce all-oral treatment regimens that include neither ribavirin nor interferon, which are both used in current treatments and cause flu-like symptoms, anemia and other side effects.

Gilead Sciences Inc, AbbVie and Bristol-Myers Squibb Co are also developing a new generation of all-oral hepatitis C treatments that in previous trials have demonstrated cure rates in excess of 90 percent, while cutting treatment duration to 12 weeks with few side effects.

Gilead, which later this year could have a one pill, once a day two-drug regimen approved in the United States, is widely perceived by Wall Street to be the best of the bunch with some analysts forecasting annual sales of $9 billion or more.

Merck is a bit behind the other three companies in its development timeline, but could prove to be the one that gives Gilead a run for its money as it aims to also produce a one pill, once a day regimen. The AbbVie and Bristol-Myers programs involve more pills and more drugs, but equally impressive cure rates so far in clinical testing.

"Merck has begun a Phase III trial in (previously untreated patients) using one pill, once per day. This should increase everyone's confidence that Merck really has a regimen competitive with Gilead's," ISI Group analyst Mark Schoenebaum said in a research note.

The Merck anti-viral medicines, which hamper the virus' ability to replicate in different ways, were tested in patients who had the genotype 1 form of the virus - the most prevalent and considered the most difficult to treat.

The most common side effects seen with the Merck drugs were fatigue, headache and nausea.

An estimated 170 million people are believed to be infected with hepatitis C worldwide. If left untreated, the progressive disease can lead to cirrhosis, liver cancer or the need for a liver transplant.

(Reporting by Bill Berkrot; Editing by Bernard Orr)

Press Release

Merck Announces Results from Studies Evaluating Investigational Hepatitis C Treatments, MK-5172 and MK-8742, in Treatment-Naïve Patients with Genotype 1 Infection

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
(12 Weeks)
(N =44)
    MK-5172 + MK-8742 + RBV
(12 Weeks)
(N = 85)
    MK-5172 + MK-8742 +
(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
      MK-5172 50 mg
with PR
      MK-5172 100 mg
with PR
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

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 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 (

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

No comments:

Post a Comment