The HIV fusion inhibitor Fuzeon (also known as T-20 or enfuvirtide) received scientific approval by the EMEA, the European Union’s drug regulatory agency, yesterday, just one week after the United States approved the drug. Marketing approval is likely to follow in approximately two months, and the drug may be available for prescription in France, Germany and the United Kingdom very soon afterwards.
However, in other European countries such as Spain where pricing negotiations can delay the introduction of new agents, the high price of Fuzeon in comparison with other antiretrovirals may delay the introduction of the drug if governments baulk at the cost.
Fuzeon has been approved for use in patients who have experienced failure of at least one drug from each class of currently licensed antiretrovirals (nucleoside analogues, protease inhibitors and NNRTIs), or for those in whom intolerance to agents from a particular class makes it difficult to construct a viable drug regimen.
Despite evidence from the TORO-1 and TORO-2 studies showing that baseline susceptibility to a greater number of agents in the background regimen predicted a successful response to T-20, the EMEA’s scientific committee has made a relatively weak recommendation regarding the use of resistance testing to optimise the background regimen when starting T-20 treatment. The committee’s statement notes only that “where available, resistance testing may be appropriate”.
However, the committee does emphasise that T-20, the most complex anti-HIV drug to administer, should only be prescribed by doctors experienced in HIV treatment.
Treatment-experienced patients receiving T-20 plus an optimised background regimen were significantly more likely to achieve viral load below 400 copies/mL at week 24 (31.7% of the T-20 group compared to 16.4% of the optimised background group), and had a significantly lower risk of virologic failure after week 6, according to findings from the TORO-1 study published last week in early release form by the New England Journal of Medicine.
According to a Roche statement released yesterday, "the preliminary 48 week analysis [of pooled data from TORO-1 and TORO-2] shows that for patients on the Fuzeon-containing arm who achieved a reduction in HIV to below detection (less than 400 copies/ml) by week 24, 80% maintained this response at week 48. Significantly fewer patients on the control arm achieved a reduction in HIV to below detection by week 24, and of these 68% maintained this response at week 48. Overall the proportion of all patients achieving Fuzeon arm (30%) compared to the control arm (12%)."
Bacterial pneumonia risk highlighted
Like the US Food and Drug Administration, the EMEA has warned that a higher risk of bacterial pneumonia may exist in patients who receive T-20. A preliminary analysis of longer term safety data has identified an increased rate of some bacterial infections, primarily pneumonia, in patients treated with T-20.
In the two phase III studies, 4.68 pneumonia events per 100 patient years of T-20 treatment were recorded, compared to 0.61 events per 100 patient years of treatment in the optimised background arm. Risk factors included low CD4 cell count, high viral load at initiation of T-20 treatment, intravenous drug use, smoking, and a prior history of lung disease.
Roche has been asked to investigate whether T-20 has any immune suppressive effect that might account for these events.
Doctors and patients are also warned that T-20 can occasionally cause serious systemic allergic reactions, which may recur on rechallenge.
According to the US FDA, symptoms of a serious systemic allergic reaction with T-20 can include: trouble breathing, fever and skin rash, chills, vomiting and low blood pressure. Patients taking T-20 should contact their healthcare provider right away if they get any of these symptoms.
Two cases have been seen so far in the combined TORO-1 and TORO-2 studies after patients follow-up of between 24 and 48 weeks. In both cases the individuals were also taking amprenavir, a drug also associated with hypersensivity reactions. In one case onset occured after eight days; in the other, onset did not occur until day 57 of therapy, in a patient with a history of allergy. In both cases, rechallenge resulted in recurrence.
Further information on this website
Fuzeon fury: price of first FDA-approved HIV fusion inhibitor sparks protest in US - news report on last week's US decision
T-20 to sell at 18,980 euros: most expensive HIV drug yet - news report on likely European price
US Food and Drug Administration documentation on Fuzeon
Lalezari J et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. New England Journal of Medicine, 2003 (early release article available online - click here for full text if you are a subscriber)