Paradigm shift in AIDS
Perhaps because there is no controversy or hint of scandal associated with the product, an FDA advisory committee's unanimous endorsement last week of Isentress raltegravir from Merck & Co. Inc. barely registered on media radar screens. But the Antiviral Drugs Advisory Committee meeting sets the stage for the second first-in-class HIV therapy approval in 2007 and what will likely be a paradigm shift in AIDS treatment.
Isentress, which has a mid-October PDUFA date, would be the first marketed integrase inhibitor.
By itself the compound would be a substantial addition to the AIDS armamentarium. But by a fortuitous convergence, its market entry would be bracketed by a cluster of HIV treatments. Another first-in-class drug, Selzentry maraviroc from Pfizer Inc. (PFE, New York, N.Y.), was approved in August, and a new-generation protease inhibitor, Prezista darunavir from the Tibotec Pharmaceuticals Ltd. subsidiary of Johnson & Johnson (JNJ, New Brunswick, N.J.), got the green light last year.
Isentress, Selzentry, Prezista and the anticipated 2008 approval of Tibotec's etravirine non-nucleoside reverse transcriptase inhibitor (NNRTI), have created new hope for salvage patients as well as the prospect of simpler, more effective interventions earlier in the disease process (see "HIV Pipeline").
Anticipation of the wave of approvals has already changed practice patterns and goals.
Previously, the best that could be done for patients who developed multi-drug resistance was to attempt to deal with the constellation of AIDS-related diseases that are the inevitable consequence of degradation of the immune system. Now, the new drug cohort is creating the expectation that even for heavily treatment-experienced patients with multi-drug resistance, viral load can be suppressed to levels comparable to those achieved in treatment-naïve patients by standard frontline therapies.
The wave of approvals has been so eagerly anticipated that AIDS experts have been counseling physicians to hold potential active drug in reserve in cases when the patient's virus is potentially susceptible to only a single drug or drug class, in the hope that the remaining therapy