Following its recent launch in the European Union, 48 week follow-up on the new HIV fusion inhibitor T-20 (enfuvirtide, Fuzeon) in people with heavy drug experience was presented as a Late Breaker at the close of the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris today. The results, from the TORO 1 and 2 studies, support earlier data from 24 weeks follow-up.
The TORO studies randomized close to one thousand people with documented resistance to drugs from each of the three main classes, and viral load above 5,000 copies, to receive antiretroviral therapy consisting of an optimized background regimen with or without T-20. T-20 is given as a twice daily, self-administered subcutaneous injection. In this advanced patient group, the median baseline viral load was over 100,000 copies, and the median CD4 was 92 cells.
A paper from Lalezari and colleagues, in the New England Journal of Medicine earlier this year, reported 24 week results from TORO 1, which were broadly similar to the findings of its sister study, TORO 2. After six months on study treatment, those receiving T-20 were more likely to have sustained a fall in viral load of at least one log, and to have viral load suppressed below both the 400 and 50 copy cut-off. Data to 48 weeks were presented by David Cooper for the first time today.
By an intent to treat analysis, where both discontinuation and virological failure were considered to be failures, 37.4% of the T-20 arm had a viral load reduced by at least one log from their baseline value after 48 weeks, compared to 17.1% of those on optimized background alone. Proportions with viral load below 400 copies were 30.4% versus 12.0% in favour of T-20. 18.3% and 7.8% reached the below 50 cut-off; a tough measure for people with such heavy drug experience. The 48 week CD4 change was an average of 91 cells in T-20 recipients, and 45 cells in the control arm. Median time to virological failure was 32 weeks in the T-20 arm, and 11 weeks in the other. Each of these differences are significant.
Safety data
The most common adverse events associated with T-20 use are problematic reactions such as pain, soreness and redness around the injection site; termed injection site reactions. These typically occur within the first weeks of administration and, as data presented today indicate, persist throughout time on therapy. Between fifty and sixty per cent of T-20 users in TORO 1 and 2 reported mild tenderness at the injection site at any clinic visit; around 20% reported moderate pain; and 1-3% reported severe pain.
Bacterial pneumonia and lymphadenopathy (swollen glands) were also reported more frequently in T-20 users, occurrences which are so far unexplained, but which manufacturer Roche has promised to explore further in post-marketing studies. Bacterial pneumonia occurred in 6.6% of T-20 recipients in TORO, and in 0.6% of the control arm. Presenting the results, Professor David Cooper of the University of New South Wales, Sydney, said that he believed lymphadenopathy to be a result of the large amount of foreign protein injected by T-20 users over time (T-20 is a peptide).
Roche turn up more drug supply
Following their announcement in February that, owing to the complexity of the production process and scarcity of raw materials, T-20 would be priced at close to £13,000 per year, Roche chose yesterday to make public their unexpectedly rapid progress in manufacturing supplies of the drug. Having forecast in Spring that this year’s output would stretch to just 12-15,000 patients, it seems Roche now expect to have enough T-20 for 18,000 people by the end of this year.
Cooper D et al. Enfuvirtide TORO studies: 48 week results confirm 24 week findings. 2nd IAS Conferenec on HIV Pathogenesis and Treatment, Paris July 13-16, LB2, 2003.