Treatment Issues Vol. 11, no. 2

GAY EN' HE LTH RISS l s NE SLE TE O LUXP ME VALANUMBTER 45 API S9

Roche Brings New Formulation of
Saquinavir To FDA
by Jill Cadman

On May 12, Hoffmann-La Roche announced that it
was applying to the FDA for approval of the long
awaited "soft gelatin capsule" formulation of
saquinavir. The soft gel capsule contains the protease
inhibitor saquinavir blended with a proprietary lipid
mixture that raises intestinal absorption of the compound to 12% of the total drug available, three times
the abysmally low 4% observed with the hard capsule.
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. Sixteenweek 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 The "protease inhibitor
and would probably be limited to.0
specific drug combinations initially you can live with Is
(in particular, 400 mg saquinavir plus beingreplaced.
400 mg ritonavir), rather than a g
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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