FDA approves maraviroc for adults with HIV

Approval represents the first new drug class in 10 years and promising therapy for treatment-experienced patients.

Issue: September 2007

The FDA approved maraviroc in 150 mg and 300 mg tablets as the newest treatment for adults with HIV, last month. Maraviroc is the first CCR-5 co-receptor antagonist, representing the first therapy in a new class of drugs.

Maraviroc (Selzentry, Pfizer) received FDA priority review. The drug is now approved for treatment of adults with CCR5-tropic HIV-1, evidence of viral replication and HIV strains resistant to multiple antiretroviral agents.

“Remarkably, maraviroc is the first oral anti-HIV medication in a new class to be approved by the FDA in more than 10 years,” said Elizabeth Connick, MD, associate professor of medicine at the University of Colorado Health Sciences Center and director of the University of Colorado Center for AIDS Research Immunology Core, both in Denver. Connick is also a member of the Infectious Disease News editorial advisory board.

Maraviroc is unique in that it blocks a host molecule, chemokine receptor 5 (CCR5), which is used by the virus to enter cells. It is recommended in combination with other antiretroviral medications for treatment–experienced patients with drug–resistant virus.

An estimated 50% to 60% of patients who have previously received HIV medications have circulating CCR5-tropic HIV-1.

“These patients constitute a significant minority of HIV-1-infected patients and have limited treatment options,” Connick said. “Not all patients with drug resistant HIV-1 will respond to maraviroc; a subset will have strains of HIV-1 that use another chemokine receptor, CXCR4.”

Connick said screening patients prior to prescribing maraviroc is essential. “It is important to screen these patients out by testing their virus to determine its chemokine receptor usage prior to prescribing the drug,” she said. “Nevertheless, for treatment experienced individuals with drug resistant HIV-1, maraviroc represents an important advance in care.”

The FDA approval is based on safety and efficacy data from two double blind, placebo-controlled studies. Trial participants (n=1,076) were selected because of detectable CCR5-tropic HIV. During the two 24-week trials, 840 patients received maraviroc. Both studies were conducted with patients who had a history of treatment with advanced, class-3 antiretrovirals (NRTI, NNRTI, PIs or fusion inhibitors, specifically enfuvirtide) but showed evidence of replication despite ongoing antiretroviral therapy.

“This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options,” said Steven Glason, MD, MPH, director of FDA’s center for drug evaluation research, in press release.

Product safety

Several safety points should be considered when initiating therapy with maraviroc. Tropism and treatment testing should guide use and use of maraviroc is not recommended in patients with dual/mixed or XXCR4-tropic HIV as efficacy was not demonstrated in a phase 2 study of the patient group. Safety and efficacy of maraviroc has not been established in antiretroviral naive adult and pediatric patients.

The product label includes warnings about hepatotoxicity and a statement of the possibility of myocardial infarctions in the warnings sections. The recommended dose of maraviroc differs based on concomitant medications due to drug interactions. Maraviroc can be taken with or without food.

Maraviroc has not been tested or studied in pregnant women. The FDA recommends HIV positive women should not breast feed, whether or not they are on antiretroviral medications.

The most common adverse events associated with maraviroc are cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain and dizziness. – by Kirsten H. Ellis

For more information:

Visit Pfizer’s website for maraviroc prescription information at http://media.pfizer.com/files/products/uspi_maraviroc.pdf