Genentech Inc. and partner XOMA Ltd. are expected to receive a favorable recommendation on the biologics license application for Raptiva, a proposed treatment for adults suffering with moderate to severe plaque psoriasis.
The companies are scheduled to present the BLA before the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee in Gaithersburg, Md., today. The FDA is not bound by the committee's recommendation.
On Monday, FDA reviewers released a 148-page briefing document describing and analyzing the six Phase III trials conducted by the companies in support of Raptiva's (efalizumab, formerly Xanelim) safety and efficacy in those 18 years and older.
The agency document does not include a recommendation from reviewers. In fact, Mike King, managing director with Banc of America Securities in New York, described the package to BioWorld Today as "very benign and straightforward - there's no smoking gun."
King believes Genentech, of South San Francisco, Calif., and XOMA, of Berkeley, Calif., will leave the meeting this afternoon with a vote of approval. "This should be a pretty easy process," he said. "The risk-benefit looks very much skewed in Raptiva's favor."
Regarding the safety of Raptiva, FDA reviewers reported that malignancies in the placebo-controlled portion of the trials were few, and not higher in the treated portion of the trials. But the trials demonstrated a higher percentage (0.4 percent vs. 0.1 percent) of serious infections in the treated arm compared to placebo, according to the FDA. Some infections were pneumonia, sepsis or seeding of distal sites.
Genentech officials were not answering press questions a day in advance of the meeting. However, the company previously said it expected FDA action on Raptiva sometime in October. The application was filed in December. (See BioWorld Today, Dec. 27, 2002.)
If approved late this year and launched in early 2004, King said U.S. sales could reach $178 million in 2008.
Raptiva, a subcutaneous injection, is a humanized monoclonal antibody and targeted T-cell modulator, designed to inhibit the inflammatory cascade in psoriasis. Specifically, it works by blocking the binding of LFA-1 to ICAM-1, inhibiting the T cells from binding to key cells in the psoriasis cascade, rather than depleting T cells.
All told, according to the companies, Raptiva has been studied in 13 psoriasis clinical trials in which 2,762 participants were treated with the drug. Four of the Phase III studies were placebo-controlled while two were open label.
Patients treated with Raptiva experienced rapid, clinically meaningful and statistically significant benefits across every measured endpoint in all Phase II and III trials, the companies reported in their briefing document. Furthermore, Raptiva patients had fewer psoriatic skin lesions, less itching and improved quality of life.
After 12 weeks of treatment, the companies said 27 percent of patients had PSAI-75 (greater than 75 percent improvement in Psoriasis Area and Severity Index) improvement while 59 percent of patients had a PSAI-50, compared with placebo rates of 4 percent and 14 percent, respectively, the companies said.
The companies said Raptiva's efficacy improves with continuous treatment after 12 weeks. After 24 weeks of Raptiva treatment, 44 percent of patients had PASI-75 improvement and 66 percent of patients had PASI-50 improvement.
If Raptiva makes it to market, it will be entering a field of growing competition.
Other psoriasis products include Cambridge, Mass.-based Biogen Inc.'s Amevive (alefacept) and Thousand Oaks, Calif.-based Amgen Inc.'s Enbrel (etanercept). Enbrel is approved for psoriatic arthritis and is often used off label in psoriasis. (See BioWorld Today, Feb. 3, 2003, and Sept. 16, 2002.)
Enbrel, a TNF blocker, is being considered by the FDA as a treatment for psoriasis.
When asked how Raptiva would compare with Enbrel and Amevive, King said "better than Amevive, but not as good as Enbrel."
He said Raptiva would have efficacy and convenience similar to Enbrel, but because it's a new entity, it would not have the safety database of Enbrel.
Other TNF blockers under development in psoriasis are Remicade (infliximab), made by Centocor Inc., of Malvern, Pa., and Humira, Abbott Laboratories' product for rheumatoid arthritis.
Genentech and XOMA had intended to file the Raptiva BLA in late 2001, but were delayed when the FDA requested a pharmacokinetic study to confirm the equivalence between materials used for testing and manufacturing. That was the result of medications made in the transition from small-scale to large-scale production. (See BioWorld Today, Oct. 8, 2001.)
The companies suffered a few months later when preliminary data from the study came back looking bad. XOMA's stock dropped 42.1 percent, or $3.21, to close at $4.42 on that news, while Genentech's fell 8.8 percent, or $4.29, to close at $44.70. (See BioWorld Today, April 8, 2002.)
Genentech and XOMA share rights to Raptiva in the U.S. Serono SA, of Geneva, has rights outside the U.S., except in Japan, where Genentech has rights. Serono filed for European regulatory approval in late February.
Under the Genentech-Serono arrangement, Genentech will receive milestones and royalties between 15 percent and 20 percent on Raptiva sales, with royalties of about 5 percent from Genentech to XOMA. (See BioWorld Today, Feb. 7, 2003.)
Genentech's stock (NYSE:DNA) closed Monday at $83.52, up $2.77, while XOMA's (NASDAQ:XOMA) closed at $9.40, up $1, or 11.9 percent.