Sometime in the next year—when details are ironed out—QLT Inc., Vancouver, Canada, plans to launch Aczone (dapsone 5%
gel) for the topical treatment of acne vulgaris. The product was approved in July, but QLT is pondering how best to work with
the labeling required by the Food & Drug Administration. "We might wait [to launch] until we have phase IV data," said Mohammed
Azab, M.D., chief medical officer of QLT. Phase IV trials evaluating this issue are slated to begin this year.
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Aczone, which utilizes solvent microparticulate (SMP) technology to make its active ingredient dapsone (which is extremely
insoluble) effective topically, has been tested in more than 3,000 patients with acne of varying severity. Clinical trial
results document its efficacy in reducing the number of lesions—by 46% to 48% of inflammatory lesions and by 30% to 31% in
non-inflammatory lesions—over the 12-week trials. While the gel's mechanism of action in acne is unknown, Azab believes its efficacy results from the drug's proven anti-inflammatory
and antibacterial properties. "There are three driving factors in the pathogenesis of acne: increased sebum production, bacterial
infection, and inflammation," he said. "Topical dapsone may well address two of these three factors. Existing products typically
combine a drying agent with an antibacterial agent."
Topical dapsone gel appears to have a clean safety profile. Azab noted, "The systemic absorption of dapsone from the topical
formulation into the blood is quite low. It's at least 100-fold less than a dose of oral dapsone." According to the package
insert, dapsone topical gel is only minimally absorbed: At day 14, the mean AUC0-24h for topical absorption for the 5% gel was 415 ±224 ng·hr/mL in comparison with a single 100-mg oral dose of dapsone AUC0-infinity = 52,641 ±36,223 ng·hr/mL. "In over 3,000 patients, there was no significant difference in any of the adverse events you
would expect from dapsone between the treated and the vehicle groups," Azab said. Because of its concern over the safety of topical dapsone—based on the safety of oral dapsone—the FDA has issued a labeling
requirement that patients need to be screened for G6PD deficiency, and patients with this deficiency must be monitored by
regular blood counts. "Dapsone is known for its potential side effect of hemolysis, especially in patients with certain common
enzyme deficiencies like G6PD," Azab said. So despite very clean data, the FDA is requiring labeling that mandates screening
of patients for G6PD deficiency. (In the clinical trial program, 1.4% of 3,500 patients had G6PD deficiency, a percentage
consistent with the incidence of G6PD deficiency in the North American population.) Azab noted, however, that "the FDA left
the door open for us to conduct a phase IV study that treats G6PD patients, and, if we show that the product is safe in those
patients compared with vehicle, then it is willing to reconsider that requirement." That study will soon be under way.
QLT is also evaluating dapsone gel in conjunction with other acne therapy. "Following our submission, we conducted a randomized,
controlled phase IIIB study in which we added a drying agent to dapsone gel therapy. Using dapsone gel with a drying agent
should affect the factors that contribute to acne: inflammation, infection, and sebum production. We will be reporting these
data before the end of the year," Azab concluded.
Kathy Hitchens is a medical writer based in Indiana.
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