How antiretroviral drugs are approved

* FDA document says Selzentry “well tolerated” (“Pfizer HIV drug seems safe for new use — FDA staff”; Susan Heavey, 6 October 2009)

“Through 48 weeks, fewer participants discontinued maraviroc [generic name of Selzentry] because of toxicity (4.2%” [in a comparison against efavirenz; NIH Treatment Guidelines, 3 November 2008, pp. 36-7].

In the world of HIV/AIDS,
a medication that brings toxic effects
within 48 weeks in more than 4% of patients
is said to be “well tolerated”.

Here’s the fuller context:

“Pfizer Inc’s . . . HIV drug Selzentry appears to be safe for wider use in certain patients with the disease who have not yet begun taking any medications, U.S. Food and Drug Administration staff said in a document released on Tuesday. The drug, also know by its generic name maraviroc, is already FDA-approved in combination with similar drugs for HIV patients who have tried other antiretroviral medications. Pfizer is seeking FDA permission to market Selzentry for HIV patients who have a certain variation of HIV-1 — one of two strains of the human immunodeficiency virus that causes AIDS — who have not yet tried any medications. It would be taken with other antiretroviral drugs. An FDA staff document said the drug appeared to be “well tolerated” in patients in a company-funded study [that in itself is cause for concern, of course]. A review of an FDA database also found no new reported safety concerns [apparently the 4.2% toxicity in less than a year is not a “NEW” safety concern] in HIV patients who have already been taking the drug. . . . The FDA released the document ahead of a public meeting on Thursday when the agency will ask its outside advisers for a recommendation on whether to approve the drug’s wider use. It usually follows their advice. [How can the conclusion “well tolerated” precede the advisory panel’s discussion?] Pfizer said its trial showed the drug is safe [to 95% of patients, provided they don’t take it for more than 48 weeks] and effective.”

NIH Treatment Guidelines, 3 November 2008, regarding Selzentry (generic is maraviroc, MVC)

Table 13 —
Hepatotoxicity (clinical hepatitis or asymptomatic serum transaminase elevation):
All NNRTIs; all PIs; most NRTIs; maraviroc

Appendix Table 6:
“Side” effects include — Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension.

Pp. 36-7: Maraviroc-Based Regimen. The MERIT study compared the CCR5 antagonist maraviroc with efavirenz . . . . Only participants who had CCR5 virus and no evidence of resistance to any drugs used in the study were enrolled (n = 633). At 48 weeks, virologic suppression (defined as HIV RNA <400 copies/mL) was seen in 75.3% of maraviroc recipients and in 78.9% of efavirenz recipients, and HIV RNA <50 copies/mL was observed in 65.2% of maraviroc recipients and in 69.2% of efavirenz recipients. The HIV RNA <50 copies/mL results did not meet the criteria set by the investigators to demonstrate noninferiority for maraviroc in this study. CD4 counts increased by an average of 170 cells/mm3 in the maraviroc arm and by an average of 143 cells/mm3 in the efavirenz arm. Through 48 weeks, more participants discontinued maraviroc because of lack of efficacy (11.9% vs. 4.2%), whereas fewer participants discontinued maraviroc because of toxicity (4.2% vs. 13.6%).