By Brady Huggett
Genentech Inc. and XOMA Ltd. released positive preliminary results from their two pivotal Phase III trials of Xanelim in patients with moderate-to-severe plaque psoriasis, and expect to file a biologics license application perhaps as early as year¿s end.
Both trials hit their primary endpoint of achieving a 75 percent or greater improvement in Psoriasis Area and Severity Index scores over placebo. The companies will continue to analyze data as the trial extends beyond the 12-week period, as well as monitor the two other Phase III trials ¿ a retreatment trial and a one-year continuous trial ¿ both now under way.
While the initial 12-week data were good, it is the revelations from the other trials that will determine filing.
¿What we need now is not so much related to the 12-week data ¿ that was fine,¿ said Peter Davis, chief financial officer at Berkeley, Calif.-based XOMA. ¿But what remains to be seen now is this retreatment data and dosability schemes. We want to have as comprehensive a safety package as we can to take to the FDA. From a practical point of view, we want to be as confident of the safety and efficacy data before launch as opposed to after launch.¿
The two double-blinded, placebo-controlled trials involved more that 1,000 patients at about 80 sites in the United States. Patients enrolled were aged 18 to 70 and had plaque psoriasis covering a minimum of 10 percent of total body surface area. Full data from the extended part of the trial will be presented at upcoming scientific meetings, said Wendy Emmanuel, corporate communications spokes-woman for Genentech.
¿We are pleased with the initial results from the studies and the programs are continuing and progressing according to our internal schedule,¿ she said. ¿We plan to evaluate the data that comes in through the rest of the year, make a BLA filing decision later this year, and, pending favorable data analysis, file a BLA before year end or the first quarter of next year.¿
Genentech and XOMA have co-developed Xanelim since they began their $35 million collaboration in 1996. XOMA paid for Phase I and II trials, Davis said, but once the product got into Phase III trials and for everything beyond, Genentech pays 87.5 percent and XOMA 12.5 percent. (See BioWorld Today, April 23, 1996.)
¿And they lend us that 12.5 percent,¿ Davis said. ¿Once the product is approved, we go into a 75 percent [for Genentech] and a 25 percent cost-sharing and profit-sharing plan in the United States.¿
For the rest of the world, XOMA will get royalties in the mid-single digits. Genentech, of South San Francisco, will make marketing decisions.
¿Genentech is planning to market Xanelim in the United States and is seeking a partner outside the U.S.,¿ Emanuel said.
Xanelim, a humanized monoclonal antibody, is designed to inhibit the binding of T cells to other cell types and to target three psoriasis processes. First, it can inhibit the binding of T cells through interactions with adhesion molecules on the endothelial cell surface. Also, it can affect trafficking of T cells into the skin. Finally, it is designed to inhibit the activation of T cells. All three processes may contribute to abnormal skin cell growth and lesions.
The results from the 12-week portion of the trial were all but expected, based on the positive results seen in Phase I and II trials, Davis said. Those results lent themselves to a cautious optimism regarding Phase III, but as Davis pointed out, the battlefield is strewn with optimistic companies.
¿[The results] were not surprising to us because the results have been consistent all along,¿ he said. ¿But that is why you run the trials. It¿s like a highly favored football game ¿ you still play it. We have seen from our earlier trials good results and that gave us confidence going into Phase III. We are hopeful that the follow-on arms will be as equally positive.¿
Genentech¿s stock (NYSE:DNA) rose $1.45 Thursday to close at $51.15. XOMA¿s stock (NASDAQ:XOMA) jumped $1.05, or about 9 percent, to close at $12.75.