Very rapid European approval of drugs for salvage therapy could be a reality by the end of this year, if proposals of a French working party are adopted by the European Union's drug licensing body, the EMEA.
The proposals, first outlined by Dr Daniel Vittcoq at last month's salvage therapy workshop in Chicago, focus on making drugs available for people who have run out of other treatment options. The proposals may affect licensing submissions for Abbott's ABT-378, Gilead's tenofovir and Roche's T-20 within the next year, which means that these drugs could be available in Europe before they are licensed in the United States.
The agency is considering whether to license drugs for salvage therapy on the basis of very short trials (lasting 16 weeks) that show effectiveness of new drugs in individuals with extensive treatment experience and rising viral load.
For example, the committee is considering whether to license drugs on the basis of studies which switch people from a failing regimen to monotherapy with a new compound for 10-14 days in order to assess the speed and magnitude of viral load decline. After this period the failing regimen will be re-introduced and the durability of the viral load decline might be assessed over 12 or 16 weeks.
Another possibility is that people on a failing regimen will be randomised to receive new drugs chosen on the basis of their treatment history and the new compound or placebo. Again, the trial would last only 12-16 weeks.
Current practice for licensing drugs that might be useful in salvage therapy is to demand data from 24 week studies which are active in people failing current therapy, or which have offer advantages in terms of tolerability or pharmacokinetic profile.
The endpoints used to assess the performance of the drugs will be the impact on viral load, and also treatment effect in people with high viral load, performance of the drugs according to baseline resistance profiles, and the correlation between virological impact and drug levels (pharmacokinetic parameters). The working party is likely to recommend that new agents should be able to reduce viral load by 0.5 to 1 log by 12 or 16 weeks.
The committee is also considering how to evaluate studies that test several new agents at once. The committee is concerned that new drugs should only be combined when the optimal dose of each drug is well defined, and when the pharmacokinetic interactions have already been characterised. Additive toxicity is also a concern; for example, will two drugs used together have much greater effects on lipid levels than each drug used alone?
The European move runs in the opposite direction to American views on the licensing of drugs, which have become more conservative as concerns grow over the incidence of serious long-term toxicities associated with HAART.
The CPMP will make a final decision on its approach to licensing new compounds for salvage therapy at its meeting in July or September, but the committee will not be altering the guidelines for assessment of new compounds for first-line therapy.