By Mary Welch

Staff Writer

Genentech Inc. and Xoma Ltd. started a Phase III trial of their anti-CD11a (hu1124) product, a recombinant humanized monoclonal antibody for treating moderate to severe plaque psoriasis. Another Phase III trial is set to begin in the first quarter of 2000.

"Our first Phase III started in mid-December and will involve about 30 sites in the U.S. and Canada," said Ellen Martin, director of corporate communications for Berkeley, Calif.-based XOMA. "The two studies will overlap."

Each trial will last 12 weeks, but Martin declined to say how many patients will be involved. The trials will be similar to the Phase II studies except in the dosing schedule and administration.

"The endpoints are similar," she said. "However, the Phase II trial was an eight-week trial. The Phase III will be 12 weeks. In addition, the Phase III trials will be given by subcutaneous administration vs. intravenous in the Phase II trial. That's very important because a subcutaneous administration is more comfortable for the patient. Eventually, it is our hope that patients can administer it themselves. It'll become an easier, outpatient treatment."

In the Phase II trial, the anti-CD11a antibody showed highly statistically significant improvement in patients. The randomized, double-blind, placebo-controlled trial done in Canada tested the antibody in 145 patients. The primary endpoint was fair or better improvements in a physician's global assessment (PGA) score, with fair meaning 25 percent. The company also measured "good" (50 percent improvement) and "excellent" (75 percent). The score represents improvement of clinical signs and symptoms, as compared to baseline in a six-point scale. The data showed 48 percent of patients treated with the 0.3 kilogram dose had a PGA score at 56 days of at least 50 percent improvement compare to 15 percent of placebo patients (p=0.0002). Twenty-five percent had a PGA score of 75 percent or greater improvement, compared to 2 percent among placebo patients (p=0.0004). (See BioWorld Today, July 8, 1999, p. 1.)

Anti-CD11a is a humanized antibody designed to prevent activation of T cells and their migration to sites of inflammation. It has potential applications in organ transplant rejection and in certain inflammatory disorders, such as psoriasis. In fact, a Phase I study in kidney transplantation will begin in the first quarter of 2000 as well.

Xoma and South San Francisco-based Genentech started their collaboration in 1996 in a deal valued at $35 million. At the time, Genentech purchased $9 million in Xoma stock, but Martin said some of that stock has since been sold. Xoma received a milestone payment when the antibody entered Phase II but does not receive one for the initiation of Phase III trials. (See BioWorld Today, April 23, 1996, p. 1.)

The companies funded the research efforts in a 75-25 split, with Genentech paying the larger share. However, Genentech lent Xoma the money in the form of long-term convertible loans that could be paid back in cash, stock or through royalties. "We're hoping we can pay them back from our share of the royalties," Martin said.

The collaboration has been a fruitful one, she said. "Genentech had more good discoveries and not enough resources to fully develop them. We had expertise in monoclonal antibodies as well as clinical and manufacturing capabilities. It was a logical marriage and it's worked out well. We've moved the antibody quickly through trials."

This is the second start of a Phase III trial for Genentech this month. Last week it said it was staring Phase III trials of its recombinant humanized monoclonal antibody to vascular endothelial growth factor (rhuMAb-VEGF) in combination with chemotherapy in metastatic colorectal cancer and metastatic non-small-cell lung cancer. (See BioWorld Today, Dec. 17, 1999, p. 1.)

Genentech's stock (NYSE:DNA) closed Monday at $124, down $1.062. Xoma's stock (NASDAQ:XOMA) closed Monday at $2.750, up 6.25 cents.