Bay Area Reporter - August 9, 2007
Bob Roehr

The main caveat is that the drug only works against virus that uses the CCR5 coreceptor. The FDA recommends that maraviroc only be used after a test has been done to determine that the patient only has virus using the CCR5 coreceptor. The drug should be part of a combination therapy regimen.

Clinical trials for maraviroc were conducted using the Trofile CCR5 coreceptor assay developed by Monogram Biosciences. The FDA also approved commercial use of that test on August 6. However, cost is an issue. Reports are that the list price for the assay is a steep $2,000, with a discount for government programs that could bring it down to about $1,500.

The list price for maraviroc is $29 a day, or more than $10,500 a year. That is similar to second-generation protease inhibitors that have been developed to treat experienced patients.

The Fair Pricing Coalition, an ad hoc group of HIV activists that works with the pharmaceutical industry on pricing issues, expressed "dismay and disappointment" with the price.

"Pfizer chose a conventional pricing strategy, which amounts to 'whatever the market will bear,'" said Lynda Dee. She is with AIDS Action Baltimore and met with Pfizer. She called for government imposed price controls on expensive drugs.

Project Inform's Martin Delaney said, "The best way to use this drug has yet to be determined. It requires the use of an expensive diagnostic test at least once, if not more often. Given this and the other limitations it faces, we feel that the company's pricing strategy is inappropriate and unwarranted."

The FDA had granted Pfizer an approval in principle for maraviroc on June 20, in order to meet a fast track regulatory deadline. But a late reported incident of liver toxicity contributed to the delay in issuing a full approval. The FDA also resulted the addition of a "black box" warning, to monitor for that possible toxicity, to the drug label.

Because the drug is the first in its class, and there is incomplete knowledge of the role that CCR5 plays in immune function, Pfizer has agreed to create a data safety base and monitor use for at least five years.

How it works

HIV enters the cell by grabbing on to a CD4 receptor, then on to a coreceptor, either CCR5 or CXCR4. Generally people who are recently infected have R5 virus and the X4 variation emerges as disease progresses. But there is still a great deal of controversy about that; individuals can vary tremendously and the only way to tell for sure is to have a tropism test performed on a blood sample of the virus.

The clinical trials for maraviroc involved 840 patients who were heavily treatment experienced and needed other options. A tropism test was used to screen their virus and about half were found to still have virus that only used the CCR5 coreceptor.

Physicians in the trial used resistance data to create an individualized optimized background therapy (OBT) and then the patients were randomized to receive placebo or maraviroc twice a day.

At the end of 24 weeks, more than half of the patients on maraviroc had a viral load that was below 400 copies, compared with less than a third of those who received OBT plus placebo. Their CD4 cell counts increased by more than 100, twice as much as the increase of those in the placebo arm of the study. Side effects in the two groups were comparable.

Results from a trial in treatment naive patients were presented last month at the AIDS conference in Sydney. It compared 360 patients on a regimen of efavirenz (Sustiva) and Combivir with 361 patients on a regimen of maraviroc and Combivir. The results were good but not spectacular; 69.3 percent and 65.3 percent of patients, respectively, suppressed their viral load below 50 copies.

Pfizer will be seeking approval of the drug in treatment naive patients and it is likely to be granted, probably next year. But maraviroc is not likely to be eagerly embraced by physicians as a drug of first choice because it shows close but not superior outcomes; it does not have a track record; it must be taken twice a day; and it costs more.

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