Treatment Issues, Vol 11, No. 4/5; April 1997
Jill Cadman

The recommended dose of the new version is 1,200 mg three times a day (TID), compared to 600 mg TID for the hard capsules. Taking this much will require 18 saquinavir soft gel capsules per day and provide eight to ten times the drug exposure of the current formulation. The eight-week dose-ranging study (NV15107) that identified 1,200 mg TID as the preferred dose recorded a respectable, though hardly record-breaking, 1.43 log (96.3%) drop in viral load among 22 volunteers on saquinavir monotherapy.

The safety study (NV15182) showed few adverse side effects with the new formulation, but caution should be advised for those with a history of liver disease. In addition to the safety data, the FDA has recently requested a head-to-head activity study comparing the two formulations to prove that the soft gel is an enhancement over the hard capsule. Sixteen week activity data from this study (NV15355) should be available by mid-summer and will be submitted to the FDA during the review process. Roche expects to receive the FDA's go- ahead to market the improved saquinavir by the end of this year.

Community activists have raised concerns about the continuation of Roche's aggressive marketing campaign which is advertising saquinavir as "a protease inhibitor you can live with." The hard capsules are administered at 600 mg TID, a suboptimal dose that may breed resistance to both the new formulation and other protease inhibitors by failing to have much impact on HIV replication. At a community meeting in May, activists asked Roche to pull the campaign until the soft gel capsules are available. Tammy Lewis, Product Director for saquinavir, conceded that the best way to use the current formulation is in combination with the protease inhibitor ritonavir, which raises blood levels of saquinavir ten-fold by blocking the drug's metabolism in the liver. But the saquinavir/ritonavir combination has not been reviewed, much less approved, by the FDA, and Roche is prohibited from promoting it.

Roche is now pursuing approval of an expanded indication of saquinavir for use in combination with other protease inhibitors. Approval is not likely within the next 12 months and would probably be limited to specific drug combinations initially (in particular, 400 mg saquinavir plus 400 mg ritonavir), rather than a broad saquinavir/other protease inhibitor indication. Discussions have already taken place between Roche, Abbott and the FDA regarding registration trials in Europe for saquinavir/ritonavir.

Another long-standing community complaint is the current price of saquinavir. At $5800 per year wholesale, the hard capsule saquinavir is at least as expensive as the other protease inhibitors even if it is the weakest. Ms. Lewis says it is "premature" to comment on the pricing of the soft gel capsule. Especially at the preferred 1,200 mg TID dose, the soft gel could prove much more costly than the present version.

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