In the news ... 2007

Selzentry Gets Approved

August 8, 2007

Over a month after receiving an ‘approvable’ letter from the Food and Drug Administration (FDA), Pfizer has announced that it has received accelerated approval for its oral entry inhibitor, Selzentry (maraviroc). According to the company’s press release, the drug will be widely available in US pharmacies by the middle of September.

Selzentry works by blocking HIV from attaching to a protein, called CCR5 or R5, on the surface of some immune system cells. Some HIV, called R5 HIV, uses this protein to enter and infect immune system cells. Other strains of HIV can use another receptor called CXCR4 (X4 HIV). People can also have HIV that can use either R5 or X4—which is called dual tropic—or a mixed population, called mixed tropic.

Selzentry is approved for use in combination with other anti-HIV drugs for people with R5-only HIV, and evidence of detectable viral replication and resistance to multiple HIV drugs. In order to receive the drug, people will have to take a blood test that can determine if their HIV is R5, X4, dual or mixed tropic. Currently, the only available test is the Trofile assay from Monogram. Though its price hasn’t been publicly announced, we believe it will be very expensive, ranging from $1400 for government programs (like ADAP) to over $2000 for people with private insurance.

The approval of Selzentry was based on data from two trials, called MOTIVATE 1 and 2, which compared Selzentry to a placebo, when combined with optimized background therapy (a combination of the best available anti-HIV drugs chosen by a physician based on treatment history and resistance testing). On average people taking Selzentry had reductions in HIV levels of almost 2 logs (around 99%) compared to around 1 log (90%) for people taking the placebo.

The most common side effects for people taking Selzentry were cough, fever, rash, stomach pain and dizziness. There have been a few reports of liver toxicity in people taking Selzentry, so people with liver disease or a history of liver problems should be monitored closely. Also, people with any history or dizziness when standing up (called postural hypotension) should exercise caution when starting Selzentry.

The use of Selzentry will be limited by the prevalence R5-only HIV among people with extensive treatment experience. Close to half of the people who were screened for the MOTIVATE trials were excluded because they had X4, dual or mixed HIV. As reported here, another recent study of Selzentry found it to be inferior to Sustiva (efavirenz) in people taking anti-HIV drugs for the first time.

Project Inform supports the approval of Selzentry. More options for people with drug-resistant HIV are badly needed by many. While the once sky-high expectations for this drug have been tempered somewhat, studies have shown that it is fairly potent and generally well tolerated. This is the first drug to target a component of the immune system rather than HIV itself. Further studies, as well as clinical experience will give us a better understanding of the longer term use of the drug.

Selzentry works best when combined with other active drugs. FDA approval of Merck’s integrase inhibitor, Isentress (raltegravir), is expected in October of 2007. It is currently available through an expanded access program. Also available in expanded access is Tibotec’s NNRTI, etravirine (TMC-125). Along with the PI Prezista (darunavir) approved late last year, this gives almost people with highly drug-resistant HIV their best opportunity yet to build a combination with multiple active drugs. Never before have so many potent new drugs been available at the same time.