Merck Plans to Initiate Phase 3 Clinical Development Program in Second Half of 2014
BOSTON, MA, USA I March 5, 2014 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today presented data from the dose-ranging portion of an ongoing Phase 2B clinical trial of doravirine, the company’s investigational next-generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), at the 21st Conference on Retroviruses and Opportunistic Infections (CROI). Interim data demonstrating potent antiretroviral (ARV) activity for four doses (25, 50, 100 and 200 mg) of once-daily, oral doravirine in combination with tenofovir/emtricitabine in treatment-naïve, HIV-1 infected adults after 24 weeks of treatment were presented during a late-breaker oral session. Based on these findings as well as other data from the doravirine clinical program, Merck plans to initiate a Phase 3 clinical trial program for doravirine in combination with ARV therapy in the second half of 2014.
“Building on our long-standing commitment to the HIV community, Merck continues to evaluate new candidates we believe have the potential to make a meaningful difference in the lives of HIV patients,” said Daria Hazuda, Ph.D., vice president, Infectious Diseases, Merck Research Laboratories. “We look forward to advancing doravirine into Phase 3 clinical trials in the second half of 2014.”
Doravirine Clinical Data
This randomized, double-blind clinical trial examined the safety, tolerability and efficacy of once-daily doravirine (25, 50, 100 and 200 mg) in combination with once-daily tenofovir/emtricitabine versus efavirenz (600 mg), in treatment-naïve, HIV-1 infected patients. The primary efficacy analysis was percentage of patients achieving virologic response (< 40 copies/mL).
At 24 weeks, doravirine doses of 25, 50, 100, and 200 mg showed virologic response rates consistent with those observed for efavirenz at a dose of 600 mg. All treatment groups showed increased CD4 cell counts.
| |
|
|
|
Proportion of Patients with Virologic
Response at 24 weeks (95% CI)
|
|
Mean CD4 Change
from Baseline (95% CI)
|
| Treatment* |
|
Dose (mg) |
|
n/N |
|
% <40
copies/mL
|
|
cells/μL
|
| Doravirine |
|
25 |
|
32/40 |
|
80.0 (64.6, 90.9) |
|
158 (119, 197) |
| |
|
50 |
|
32/42 |
|
76.2 (60.5, 87.9) |
|
116 (77, 155) |
| |
|
100 |
|
30/42 |
|
71.4 (55.4, 84.3) |
|
134 (100, 167) |
| |
|
200 |
|
32/41 |
|
78.0 (62.4, 89.4) |
|
141 (96, 186) |
| Efavirenz |
|
600 |
|
27/42 |
|
64.3 (48.0, 78.4) |
|
121 (73, 169) |
| Missing data approach: |
|
Non-completer = Failure |
|
Observed Failure |
| |
|
|
|
|
|
*In combination with tenofovir/emtricitabine
|
The incidence of drug-related adverse events was comparable among the doravirine-treated groups. The overall incidence of drug-related adverse events was lower in the doravirine-treated groups (n=166) than the efavirenz-treated group (n=42), 35 percent and 57 percent, respectively. The most common central nervous system (CNS) adverse events at week 8, the primary time point for evaluation of CNS adverse experiences, were dizziness [3.0% doravirine (overall) and 23.8% efavirenz], nightmare [1.2% doravirine (overall) and 9.5% efavirenz], abnormal dreams [9.0% doravirine (overall) and 7.1% efavirenz], and insomnia [5.4% doravirine (overall) and 7.1% efavirenz].
Based on the 24-week data from this dose-finding study, a single dose of 100 mg doravirine was chosen to be studied for the remainder of this study, up to 96 weeks.
About Doravirine
Doravirine, also known as MK-1439, is an investigational next-generation, NNRTI being evaluated by Merck for the treatment of HIV-1 infection. In preclinical studies, doravirine demonstrated potent antiviral activity against HIV-1 with a characteristic profile of resistance mutations selected in vitro compared with currently available NNRTIs. In early clinical studies, doravirine demonstrated a pharmacokinetic profile supportive of once-daily dosing and did not show a significant food effect.
Merck’s Commitment to HIV
For more than 25 years, Merck has been at the forefront of the response to the HIV epidemic, and has helped to make a difference through our proud legacy of commitment to innovation, collaborating with the community, and expanding global access to medicines. Merck is dedicated to applying our scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HIV worldwide.
About Merck
Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside 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.
SOURCE: Merck
Post Views: 39
Merck Plans to Initiate Phase 3 Clinical Development Program in Second Half of 2014
BOSTON, MA, USA I March 5, 2014 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today presented data from the dose-ranging portion of an ongoing Phase 2B clinical trial of doravirine, the company’s investigational next-generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), at the 21st Conference on Retroviruses and Opportunistic Infections (CROI). Interim data demonstrating potent antiretroviral (ARV) activity for four doses (25, 50, 100 and 200 mg) of once-daily, oral doravirine in combination with tenofovir/emtricitabine in treatment-naïve, HIV-1 infected adults after 24 weeks of treatment were presented during a late-breaker oral session. Based on these findings as well as other data from the doravirine clinical program, Merck plans to initiate a Phase 3 clinical trial program for doravirine in combination with ARV therapy in the second half of 2014.
“Building on our long-standing commitment to the HIV community, Merck continues to evaluate new candidates we believe have the potential to make a meaningful difference in the lives of HIV patients,” said Daria Hazuda, Ph.D., vice president, Infectious Diseases, Merck Research Laboratories. “We look forward to advancing doravirine into Phase 3 clinical trials in the second half of 2014.”
Doravirine Clinical Data
This randomized, double-blind clinical trial examined the safety, tolerability and efficacy of once-daily doravirine (25, 50, 100 and 200 mg) in combination with once-daily tenofovir/emtricitabine versus efavirenz (600 mg), in treatment-naïve, HIV-1 infected patients. The primary efficacy analysis was percentage of patients achieving virologic response (< 40 copies/mL).
At 24 weeks, doravirine doses of 25, 50, 100, and 200 mg showed virologic response rates consistent with those observed for efavirenz at a dose of 600 mg. All treatment groups showed increased CD4 cell counts.
| |
|
|
|
Proportion of Patients with Virologic
Response at 24 weeks (95% CI)
|
|
Mean CD4 Change
from Baseline (95% CI)
|
| Treatment* |
|
Dose (mg) |
|
n/N |
|
% <40
copies/mL
|
|
cells/μL
|
| Doravirine |
|
25 |
|
32/40 |
|
80.0 (64.6, 90.9) |
|
158 (119, 197) |
| |
|
50 |
|
32/42 |
|
76.2 (60.5, 87.9) |
|
116 (77, 155) |
| |
|
100 |
|
30/42 |
|
71.4 (55.4, 84.3) |
|
134 (100, 167) |
| |
|
200 |
|
32/41 |
|
78.0 (62.4, 89.4) |
|
141 (96, 186) |
| Efavirenz |
|
600 |
|
27/42 |
|
64.3 (48.0, 78.4) |
|
121 (73, 169) |
| Missing data approach: |
|
Non-completer = Failure |
|
Observed Failure |
| |
|
|
|
|
|
*In combination with tenofovir/emtricitabine
|
The incidence of drug-related adverse events was comparable among the doravirine-treated groups. The overall incidence of drug-related adverse events was lower in the doravirine-treated groups (n=166) than the efavirenz-treated group (n=42), 35 percent and 57 percent, respectively. The most common central nervous system (CNS) adverse events at week 8, the primary time point for evaluation of CNS adverse experiences, were dizziness [3.0% doravirine (overall) and 23.8% efavirenz], nightmare [1.2% doravirine (overall) and 9.5% efavirenz], abnormal dreams [9.0% doravirine (overall) and 7.1% efavirenz], and insomnia [5.4% doravirine (overall) and 7.1% efavirenz].
Based on the 24-week data from this dose-finding study, a single dose of 100 mg doravirine was chosen to be studied for the remainder of this study, up to 96 weeks.
About Doravirine
Doravirine, also known as MK-1439, is an investigational next-generation, NNRTI being evaluated by Merck for the treatment of HIV-1 infection. In preclinical studies, doravirine demonstrated potent antiviral activity against HIV-1 with a characteristic profile of resistance mutations selected in vitro compared with currently available NNRTIs. In early clinical studies, doravirine demonstrated a pharmacokinetic profile supportive of once-daily dosing and did not show a significant food effect.
Merck’s Commitment to HIV
For more than 25 years, Merck has been at the forefront of the response to the HIV epidemic, and has helped to make a difference through our proud legacy of commitment to innovation, collaborating with the community, and expanding global access to medicines. Merck is dedicated to applying our scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HIV worldwide.
About Merck
Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside 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.
SOURCE: Merck
Post Views: 39
