FDA Hits Valeant’s Plaque Psoriasis Drug with a Complete Response Letter

FDA

Ortho Dermatologics, a division of Quebec-based Valeant Pharmaceuticals International, received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for its New Drug Application (NDA) for Duobrii for plaque psoriasis.

Duobrii is a combination of halobetasol propionate and tazarotene, which when used separately to treat plaque psoriasis, can only be used for four weeks or less and have a high rate of adverse side effects, respectively. However, the company published data that found the combination, because of a dual mechanism of action, had the potential for an expanded duration of use and a proven safety profile.

In April, the company published results from two Phase III, multicenter, randomized, double-blind clinical trials in the Journal of the American Academy of Dermatology. The two studies enrolled a total of 418 patients, and demonstrated that Duobrii was consistently more effective in treatment success defined as at least a two-grade improvement in an Investigator Global Assessment (IGA) score, and “clear” or “almost clear” skin. In Study 1, it showed statistically significant superiority by week four and in Study 2, by week two. In both trials, by week eight, 35.8 percent and 45.3 percent, respectively, had hit the primary efficacy outcome.

“I’ve found that psoriasis patients may benefit from combination therapy with topical agents, many of whom are unsatisfied with current treatment options,” said Linda Stein Gold, director of Dermatology Clinical Research for Henry Ford Health System in Detroit, in a statement in April. “DUOBRII is a fixed dose combination of halobetasol and tazarotene that has shown synergistic efficacy in the Phase II study. Efficacy was again demonstrated in the two Phase III studies versus vehicle with minimal side effects in a well-tolerated, patient preferred formulation.”

Although few details were released about the CRL, Valeant’s chairman and chief executive officer, Joseph Papa, said in a statement, “The CRL did not specify any deficiencies related to the clinical efficacy or safety of Duobrii and no issues with CMC [Chemistry, Manufacturing and Controls] processes. The CRL only noted questions regarding pharmacokinetic data. We are working to resolve this matter expeditiously and have already requested a meeting with the FDA. We hope to bring forward this important new treatment option for those who suffer from plaque psoriasis as quickly as possible.”

Psoriasis is a chronic, painful and often life-altering immune-mediated inflammatory skin disease. More than 75 percent of patients with moderate-to-severe plaque psoriasis have significant itching, and more than 55 percent report moderate or worse levels of pain.

Ortho has a number of projects to treat psoriasis in the works. In February, it announced the FDA has accepted its NDA for Jemdel (halobetasol propionate 0.01%). If that is approved, it will be the first high-potency topical steroid treatment for plaque psoriasis with dosing for up to eight weeks.

The FDA has set a PDUFA date of October 5, 2018, to approve Jemdel.

Also in February, Ortho inked an exclusive license deal with Kaken Pharmaceuticals Co. to develop and commercialize products with a new chemical entity, KP-470, for topical treatment of psoriasis. Valeant will have rights to develop and commercialize products with KP-470 in the U.S., Canada, and Western and Eastern Europe.

No financial terms were released. Nor were there any details about KP-470 other than it is a novel drug with an alternate mechanism of action.

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