FDA Offers Pfizer's HIV Drug Selzentry New Life -- For All the Good It Will Do

The FDA approved Pfizer’s anti-HIV drug Selzentry for expanded use in combination with other antiretroviral agents for treatment-naïve patients who are infected with only CCR5-tropic HIV-1. Contrary to company expectations, perceived limitations of this entry inhibitor could stall efforts to facilitate usage beyond salvage therapy.

The AIDS virus binds to several different cell receptors and at least one or two different co-receptors, called CXCR4 and CCR5, to enter and infect cells. The use of CCR5, CXCR4 or both co-receptors defines the “tropism” of the virus strain.

Selzentry (maraviroc) is the first of a new class of oral HIV treatments that stops the virus on the outside surface of an uninfected white blood cell instead of fighting it inside the cell like other classes of HIV medicines, principally by blocking the CCR5 co-receptor route. CXCR4 (X4) and dual HIV-1 entry is not inhibited by maraviroc. Ergo, a diagnostic test is used to confirm if a potential patient has a strain of HIV — either the CCR5 co-receptor (R5) or a combination of CCR5 and CXCR4 — that may respond to Selzentry therapy.

Granted accelerated approval by the FDA in August 2007 for treatment-experienced patients infected with the R5 HIV-1 strain, industry pundits  forecasted sales of more than $500 million by 2012. Uptake of Selzentry by HIV specialists has been less than expected — a marketing disaster — with Pfizer reporting Selzentry sales of just $46 million in 2008.

Acknowledging defeat and looking for a quiet exit — or revitalizing a tired drug with a new selling approach? On November 3, Glaxo-SmithKline and Pfizer announced the official launch of Viiv Healthcare, dedicated to the development and sales of HIV therapies, including Selzentry.

A competitive landscape dominated by Merck’s first-in-class integrase inhibitor Isentress (raltegravir) and multi-class, fixed-dosage combination therapies like Atripla (Gilead Sciences‘ two drug pill Truvada and Sustiva by Bristol-Myers Squibb) has relegated the drug to treatment-of-last resort. A roundtable of HIV specialists moderated by market researcher Panel Intelligence in 2008 did a nice job in highlighting why an entry inhibitor like Selzentry is unlikely to dominate much more than salvage treatment. Surveyed panelists prescribed the drug in approximately 3 percent to 10 percent of their patients, citing constraints such as:

• The need to do inconvenient tropism assays. These assays, which can take up to two weeks to deliver results, were unanimously identified as a barrier to greater uptake. (Next-generation tests could reportedly cut turnaround time in half to seven days or less.) Cost of this test to identify viral presence of R5, at about $2,000, was viewed as a limiting factor too.
• Drug cost and reimbursement problems can weigh on treatment planning. Selzentry could be pricing itself out of first-line usage. The drug costs about $13,140 and $26,280 per annum for 300 mg twice daily and 600 mg twice daily, compared to roughly $11,000 a year for competitive therapies. Consequently, insurance coverage variability bothered providers: some third-party payers — like BlueCross BlueShield — require time-consuming “prior authorization” before agreeing to reimbursement (a hassle doctors prefer to avoid).
• Brand awareness was low, with few HIV-patients requesting the drug by name.
• Although standard dosing of some popular drugs, including Isentress, is twice daily, providers strongly preferred once-daily dosing (Atripla).
• Long-term side effects are still unknown (although I view that as nothing more than a “smokescreen,” given at-risk prognosis of patients).
• Efficacy was not in dispute (though the drug’s effectiveness is still questioned in some circles), but consensus still dictated Selzentry was of better utility in a very specific subset of the treatment population consisting of treatment-resistant patients who tested positive for R5.

The paradigm of HIV treatment is being aggressively nudged in the direction of combination therapies, as differing mechanisms of attack likely maximize potency and diminish the risk of developing drug resistance. The supplemental FDA approval opens a second window of opportunity for Selzentry to jump through and capture some market share.

In an alternate ending of the 1962 melodrama, “Requiem for a Heavyweight,” manager Maish Rennick (played by Jackie Gleason) turns to a younger boxer and says: “You fool. You damn stupid fool. Don’t you understand? Can’t you get it into your silly head? There are only eight champions in this business. Everybody else is an also-ran.” That said, Vicriviroc, an experimental entry inhibitor — with a once a day dosing — is in a late-stage trial of treatment-resistant HIV patients being sponsored by Schering-Plough (soon to be part of drug maker Merck). If approved come 2011, the drug will likely make an also-ran out of Selzentry.