Maraviroc receives accelerated approval in US

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Regulatory authorities in the United States have granted accelerated approval to maraviroc (Selzentry in the US, Celsentri in Europe), the first drug from a new class of antiretrovirals called CCR5 inhibitors. Unlike the existing oral anti-HIV drugs which inhibit HIV replication once the virus has entered immune system cells, maraviroc works by blocking the CCR5 co-receptor on the cell’s surface. Maraviroc is expected to be available for prescription in the US in September.

Maraviroc has been approved for use, in combination with other antiretrovirals, by treatment-experienced individuals with ongoing HIV replication who have CCR5-tropic HIV. Between 50 and 60% of treatment-experienced patients have CCR5 tropic virus.

Approval of maraviroc was based upon 24-week results from the MOTIVATE studies involving highly treatment experienced individuals. These results showed that significantly more patients who received maraviroc, with an optimised background of antiretroviral drugs, achieved a viral load below 400 copies/ml and 50 copies/ml compared to individuals who received optimised background plus a placebo. Furthermore, patients in the maraviroc arms of the MOTIVATE studies also experienced greater increases in their CD4 cell count compared to the patients who were randomised to receive a placebo.

Glossary

CCR5

A protein on the surface of certain immune system cells, including CD4 cells. CCR5 can act as a co-receptor (a second receptor binding site) for HIV when the virus enters a host cell. A CCR5 inhibitor is an antiretroviral medication that blocks the CCR5 co-receptor and prevents HIV from entering the cell.

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

Food and Drug Administration (FDA)

Regulatory agency that evaluates and approves medicines and medical devices for safety and efficacy in the United States. The FDA regulates over-the-counter and prescription drugs, including generic drugs. The European Medicines Agency performs a similar role in the European Union.

tropic

When HIV selectively attaches to a particular coreceptor on the surface of a host CD4 cell. HIV can attach to either the CCR5 coreceptor (R5-tropic) or the CXCR4 coreceptor (X4-tropic) or both (dual-tropic).

replication

The process of viral multiplication or reproduction. Viruses cannot replicate without the machinery and metabolism of cells (human cells, in the case of HIV), which is why viruses infect cells.

Two twice-daily doses of maraviroc have been approved: a 150mg dose when used with protease inhibitors (with the exception of tipranavir/ritonavir), 300mg when combined with tipranavir/ritonavir or efavirenz or nevirapine. Maraviroc can be taken with or without food.

There have been concerns that CCR5 inhibitors as a class involve a risk of serious liver side-effects, and the Food and Drug Administration’s (FDA) approval from maraviroc states that the product label should include a boxed warning about liver toxicity. The warnings/precautions section of the drug information leaflet also cautions about the possibility of an increased risk of cardiovascular illness such as heart attack or dizziness when standing up quickly. The most commonly observed side-effects of maraviroc are cough, fever, upper respiratory tract infections, rash, bone and muscle problems, abdominal pain and dizziness.

The safety and efficacy of maraviroc had not been studied in pregnant women.

Full approval of maraviroc will be granted once the FDA has had an opportunity to review maraviroc’s full 48-week study data. In July, European drug regulatory authorities provided scientific approval for maraviroc, meaning that it could be available for prescription in the UK and other EU countries by November. Until its formal approval, maraviroc is available to treatment-experienced patients who would benefit from its use in an expanded access scheme.

Data on the use of maraviroc in treatment-naïve patients was presented to the recent International AIDS Society conference in Sydney. This showed that patients taking maraviroc were slightly less likely to achieve a viral load below 50 copies/ml than those taking efavirenz, but maraviroc was shown to be more tolerable.