Pfizer announced today that an international expanded access programme for its investigational chemokine antagonist maraviroc will begin early in 2007.
Maraviroc is the first of a new class of antiretrovirals called chemokine antagonists which block HIV from using the CCR5 coreceptor to gain access to CD4 cells. The drug is taken orally twice a day.
Results from a 24 week planned interim analysis of two phase III studies of maraviroc in patients with experience of all three major licensed drug classes may be presented at a major international scientific conference in early 2007, and the expanded access programme will begin to recruit patients after these data are publicly available.
Critically, maraviroc will only be available for patients who have CCR5-tropic virus. In people with HIV the virus population is predominantly adapted to using the CCR5 receptor earlier in the course of HIV disease; as the CD4 cell count falls, the virus population begins to switch to one in which use of the CXCR4 coreceptor predominates. In these patients maraviroc may have a modest positive effect on CD4 cell counts, but does not appear to reduce viral load significantly, according to results of a study presented at the Sixteenth International AIDS Conference in Toronto in August.
Pending regulatory review in participating countries, preliminary expanded access programme eligibility criteria include patients who are clinically stable with documented CCR5- tropic HIV-1 infection; at least 16 years of age (or minimum adult age as determined by local regulatory authorities or as legal requirements dictate); have limited or no treatment options available to them due to resistance or treatment intolerance; and they must be failing to achieve adequate virologic suppression on their current regimen.
The study cannot include patients who have failed prior treatment with any CCR5 antagonist in a clinical trial; have evidence of dual/mixedtropic or X4-tropic HIV; require any medications prohibited by the EAP protocol; have a condition which the study investigator deems will interfere with the patient’s adherence and safety; or who are pregnant or lactating. Investigators will select the optimized background therapy based on the patient's prior treatment history and antiretroviral resistance testing conducted according to local practice.
If national regulatory authorities agree, patients who are eligible to take maraviroc will be able to combine it with another new drug class also becoming available through expanded access, the Merck integrase inhibitor MK-0518, which has shown impressive potency in highly treatment-experienced patients.
Pfizer plans to submit licensing applications for maraviroc in the United States and Europen Union shortly, and maraviroc could be available for prescription for an undefined category of treatment-experienced patients by the second half of 2007 in the United States. When it becomes available maraviroc is likely to be the first agent of a new drug class to be approved since enfuvirtide (T-20, Fuzeon), but is likely to be more widely used by treatment-experienced patients because it is an oral drug rather than an injectable product.