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Merck discontinues vicriviroc as first-line therapy for HIV
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BOSTON — Poor phase-2 and phase-3 trial results prompted Merck to discontinue development of vicriviroc, a CCR-5 agonist for the treatment of HIV, according to study results presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy.
“Merck decided to discontinue the development of vicriviroc for the treatment of HIV infection based on the overall clinical data from phase-3 trials in treatment-experienced patients,” said Lisa Dunkle, MD, executive director of clinical research at Merck Research Laboratories. “The primary endpoint of superiority over optimized background therapy was not met.”
She also said that “results from a phase-2 trial in treatment-naive patients demonstrated that the combination of vicriviroc and atazanavir [Reyataz, Bristol Myers Squibb] did not appear to meet the current standards of efficacy for initial therapy of HIV despite promising antiviral activity and safety profile.”
Vicriviroc was initially developed by Merck, but was being developed by Schering-Plough.
The study examined the class-sparing regimen of vicriviroc plus atazanavir vs. tenofovir/emtricitabine plus atazanavir, as an initial ART regimen. The aim was to avoid toxicity associated with nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, lipid toxicity and cross-resistance to other protease inhibitors.
Eligible participants were CCR5-tropic, treatment-naive patients with HIV. The researchers randomly assigned 95 participants to one of the treatments in stage 1. Following a 24-week review of stage 1 outcomes by an external data safety monitoring board, 123 patients were randomly assigned treatment in stage 2. The final analysis involved 108 patients receiving each treatment.
The primary outcome was antiviral activity, which was defined as a drop from baseline HIV RNA levels. The main secondary outcome was efficacy, which was defined as the proportion of patients who reached less than 50 copies/mL of virus at 48 weeks.
The 48-week completion rate was 86%. The premature discontinuation rate was 23% in the vicriviroc arm and 17% in the tenofovir/emtricitabine arm. The only imbalanced reason for premature discontinuation was “adverse event” as judged by investigators during stage 1.
Of 12 protocol-defined virologic failures (defined as an inadequate response or rebound of greater than 50 copies/mL from full suppression), nine resulted from non-adherence. “No drug-resistance and few R5/X4 HIV strains were detected on drug,” the researchers wrote.
Adverse event profiles were heterogeneous among the premature discontinuations. There were no predominant adverse events in the vicriviroc arm, and there were no differences between the two arms in laboratory abnormalities.
The researchers suggested that the premature discontinuation rate may have been due to the open-label design of the trial. The premature discontinuations in the vicriviroc arm, when analyzed as failures, resulted in suppression rates that suggested lesser efficacy, according to the researchers.
“It was determined that the overall profile of vicriviroc does not appear to be an optimal agent for further study in either the treatment-experienced or treatment-naive HIV-1 patient populations,” Dunkle said.
For more information:
- Dunkle LM. H-938a. Antiviral Effect of Vicriviroc (VCV) plus Ritonavir-Boosted Atazanavir (ATV/r) Similar to Tenofovir/emtricitabine (TEM) + ATV/r but Efficacy (%<50c/mL) Inferior as Initial Therapy. Presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy. Boston, Sept. 12-15, 2010.