GlaxoSmithKline’s protease inhibitor fosamprenavir yesterday received a recommendation for marketing approval in the European Union from the Committee for Proprietary Medicinal Products.
As with the recently approved protease inhibitor atazanavir, the European drug regulatory body has approved a different dose from the one approved in the United States, reflecting a more cautious attitude towards the use of protease inhibitors without ritonavir boosting. Fosamprenavir will also be known by a different name (Telzir) in Europe from the brand name used in the United States (Lexiva).
Fosamprenavir is a prodrug of amprenavir, which means that it is converted into amprenavir during absorption. The use of the prodrug means that people need take fewer tablets in order to achieve similar levels of amprenavir when compared with the existing amprenavir formulation Agenerase.
Fosamprenavir has been approved in Europe for use in combination with low dose ritonavir. The recommended dose is 700mg of fosamprenavir twice daily with 100mg of ritonavir twice daily (in combination with at least two other antiretrovirals).
In contrast, fosamprenavir has been licensed at the following dosages in the United States:
- Fosamprenavir 1400 mg twice daily (two tablets)
- Fosamprenavir 1400 mg once daily (two tablets) with 200 mg of ritonavir (2 capsules) - only in people who have not previously taken PIs.
- Fosamprenavir 700 mg twice daily (one tablet) with 100 mg of ritonavir (one capsule).
European dosing decision driven by weaknesses in pivotal study
The Committee for Proprietary Medicinal Products notes that when compared with the lopinavir/ritonavir group in a 48 week study in treatment-experienced patients, it is possible that patients treated with fosamprenavir/ritonavir may have had an inferior degree of virologic suppression.
The results of this study, called the Context study, may have influenced European regulators to opt for a twice daily dose. The study compared once and twice daily dosing of ritonavir-boosted fosamprenavir with lopinavir/ritonavir (Kaletra). Preliminary results of the study showed that whilst the degree of virologic suppression in Telzir- treated patients was possibly inferior to the lopinavir group over the 48 weeks of treatment (potentially indicating a higher risk of drug resistance), there was no difference in the proportions of patients receiving lopinavir or fosamprenavir twice daily who had viral load below 400 copies or 50 copies at week 48 of the study.
The regulators chose not to license fosamprenavir for use without ritonavir in treatment-naive individuals, and chose not to license it for once daily use with ritonavir boosting. This may have been due to the fact that data presented to support these indications came from two studies in which unboosted and boosted fosamprenavir were compared with nelfinavir, which is proven to be inferior to lopinavir/ritonavir. In the SOLO study of once daily ritonavir-boosted fosamprenavir, nelfinavir was not inferior to fosamprenavir, although data presented at conferences from this study suggest that boosted fosamprenavir was superior to nelfinavir in people with very high viral load (above 500,000 copies/ml).
A full presentation of the 48-week data from the Context study has still not taken place more than six months after the US developer of fosamprenavir announced the key findings of the study by press release. Further information will become available when Telzir receives full marketing approval in Europe, which should take place by the end of June.
Further information on this website
Fosamprenavir (433908) shows signs of weakness in Kaletra comparison - news story, July 2003