MRK: HIV research continues in naive patients
From Biospace
Merck & Co., Inc. (MRK): Potential Remains For HIV Drug Despite Trial Disappointment
2/2/2010
New HIV treatment vicriviroc has failed to meet its primary efficacy endpoint in two Phase III clinical trials. As a result, developer Merck has opted to temporarily suspend seeking FDA approval for the drug in treatment-experienced patients. The company is, however, continuing development in naive patients where the market opportunity for the CCR5 class is considerably higher.
Although the drug was evaluated in treatment-experienced patients, a high percentage of participants were able to take three or more other active HIV drugs as part of the optimized background regimen with vicriviroc, potentially undermining vicriviroc's ability to demonstrate superiority over placebo. developer Merck will continue to study the drug in HIV patients who have not received prior treatment.
The two Phase III trials, VICTOR-E3 and VICTOR-E4, compared the safety and efficacy of 30mg once-daily vicriviroc in combination with an optimized background regimen (ritonavir boosted protease inhibitor plus at least two active drugs) against placebo. Participants were treatment experienced with documented resistance to at least two antiretroviral drug classes. While data from the study are not yet available, Datamonitor speculates that vicriviroc may have failed to achieve superiority due the inclusion of two to three active drugs in the background regimen. Efficacy rates as high as 90% have been observed in this population with the combination of currently available options, such as Merck 's Isentress (raltegravir) or Tibotec/Johnson & Johnson's Prezista (darunavir) and Intelence (etravirine). Unsurprisingly, this leaves little room for newer agents such as vicriviroc to show any additional benefits.
Vicriviroc belongs to a new class of antiretrovirals called the chemokine co-receptor 5 (CCR5) inhibitors. Pfizer's (now ViiV Healthcare's) Celsentri/Selzentry (maraviroc) is currently the only marketed drug in this class, but despite its first-to-market status, Selzentry has so far experienced a poor uptake. Its efficacy is restricted to the subset of patients infected with the CCR5-tropic strain and therefore requires a 'tropism test', which is both expensive and lengthy, taking up to a month to obtain results.
Selzentry was initially approved for experienced patients (the same group in which vicriviroc has now failed to show a benefit), of whom only 50-60% are CCR5 tropic. However, recent approval in naive patients may boost sales to some extent, given that, at approximately 80%, CCR5 tropism is significantly more common in this population. In light of this, Merck is continuing the development of vicriviroc for treatment-naive patients.
Interestingly, the company is taking a novel approach in this setting by investigating vicriviroc in combination with Bristol-Myers Squibb's Reyataz (atazanavir) and eliminating the traditional nucleoside backbone. Concerns over NRTI toxicity have led to a renewed interest in such regimens, and prescribing two agents instead of the traditional three is also likely to have cost benefits. Moreover, this strategy may be highly effective in countering the threat from developmental fixed-dose combinations such as Gilead 's Quad Pill and Gilead and Tibotec/Johnson & Johnson's Truvada/rilpivirine combination.<<
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