When trying to get a drug approved, biotechnology companies must provide the FDA with data - data showing that a drug is efficacious, that it works in the appropriate patient and that it is safe, among other things.
Genentech Inc. and partner XOMA Ltd. also had to provide data showing their psoriasis drug, Raptiva, has the same effect on patients when made with material produced by either one of the partners. A completed Phase III trial disclosed Tuesday seems to have done just that, potentially removing the final obstacle for a biologics license application filing by year's end.
"We view this as the last stumbling block," said Laura Zobkiw, corporate communications manager at XOMA. "We think that we are still on track for the filing at the end of the year. This was the one piece of the overall puzzle that we were waiting to get positive news on."
The Phase III trial - the third one conducted with Raptiva, formerly Xanelim - reached its primary efficacy endpoint of comparing the percentage of patients who achieved 75 percent or greater improvement in Psoriasis Area and Severity Index scores after 12 weeks of Raptiva therapy to placebo. The Raptiva drug used in the trial was constructed completely from Genentech materials. The data from the 556 patients with moderate to severe plaque psoriasis will be rolled into the BLA filing package that both XOMA and Genentech said should be in the FDA's hands before the new year.
Raptiva's development path goes like this: The companies hit the primary endpoints in two Phase III trials, but because of manufacturing modifications made while in the transition from small-scale to large-scale production, the FDA requested a 99-patient pharmacokinetic study of Raptiva. That study, however, did not reach a predefined statistical definition for comparability, showing that Genentech-produced Raptiva material had a higher serum concentration than XOMA-produced Raptiva material - news that dragged down XOMA's stock by 42 percent and Genentech's 8.8 percent on the day preliminary results were released. (See BioWorld Today, April 8, 2002.)
The FDA then requested that the most recent Phase III trial, which used only Genentech-produced Raptiva material, be completed. The positive results from the trial, from observers' points of view, should have washed away the companies' Raptiva troubles.
"Yes, totally," said George Farmer, analyst with Fortis Securities Inc. in New York, when asked if XOMA and Genentech have everything they need for filing. "It's the last of the pivotal Phase III trials and it used 100 percent Genentech materials. This puts everything on track for the filing of a BLA by the end of this year."
Farmer sees Raptiva on the market and helping patients by the first quarter of 2004, the same year, incidentally, his firm predicts XOMA will become profitable, although he feels that won't happen until the end of fiscal 2004.
In early August, Genentech, of South San Francisco, and XOMA, of Berkeley, Calif., said they signed a deal with Serono SA, giving the Geneva-based company rights to market Raptiva in areas outside the U.S., Japan and certain other Asian countries. Genentech and XOMA would handle U.S. sales if and when Raptiva is approved, and Genentech will push the product itself in Japan and the certain other Asian countries. Financial terms of the deal were not disclosed. (See BioWorld Today, Aug. 9, 2002.)
Serono said Tuesday it would use the most recent Phase III positive results in its own Raptiva (efalizumab) filing with European authorities, expected in 2003's first quarter.
Raptiva is a humanized monoclonal antibody and a targeted T-cell modulator. It is designed to inhibit certain inflammatory processes in the cascade of events associated with psoriasis. The product is administered intravenously, and the psoriasis market is extensive.
It's estimated that there are about 5.5 million psoriasis sufferers in Europe and about 4.5 million in the States. SG Cowen Securities Corp. estimates the U.S. market alone at $5 billion, meaning there is room for more than one therapy. And that's good, since there are several products on the psoriasis horizon. Enbrel, made by Amgen Inc., of Thousand Oaks, Calif., and Remicade, developed by Centocor Inc., of Malvern, Pa., are being developed for psoriasis, but both drugs are approved for other indications and are already being used off-label for psoriasis. Biogen Inc., of Cambridge, Mass., is developing Amevive - the drug received an 8-to-2 approval-recommendation vote from the FDA's Ophthalmic Drugs Advisory Committee in May, and Biogen received a favorable complete response letter from the FDA in June. Last week the FDA told Biogen it would finish the Amevive application, originally filed in August 2001, within six months, potentially setting up a launch in early 2003. (See BioWorld Today, May 24, 2002, and Sept. 16, 2002.)
If that occurs, Amevive would reach the psoriasis market first. SG Cowen estimates Amevive could generate $500 million in sales by 2006, but Fortis' Farmer has more faith in Raptiva, an opinion formed mainly from safety issues.
"I'm not bullish on Amevive," he told BioWorld Today. "The efficacy is definitely there, but the T-cell depletion is of concern to me.
"Put yourself in a patient's position," he added. "What if your physician tells you, I think I can cure these [psoriasis plaques], but it will be likely that it will suppress your T-cell count.' Would you want to do that? I don't think I would."
Farmer suggested Raptiva, in head-to-head market competition, would win out.
"The safety profile of the two products are going to be considered," he said. "And, [Raptiva] has a better efficacy profile than Amevive."
Putting aside any future marketing battles, the Phase III news is a good harbinger for Genentech and XOMA, and, in the end, for psoriasis patients.
"[The trial results] mean positive things for [XOMA], and its positive that we continue to meet our goals with Raptiva," XOMA's Zobkiw told BioWorld Today. "And we hope to have more successful partnerships like the one we have with Genentech down the road."
XOMA's stock (NASDAQ:XOMA) rose 49 cents Tuesday, or 8 percent, to close at $6.58. Genentech's stock (NYSE:DNA) climbed 92 cents to close at $31.75. Serono's stock (NYSE:SRA) increased 6 cents to close at $12.89.