Washington Editor

Protein Design Labs Inc. decided against pursuing daclizumab in ulcerative colitis after a Phase II trial in the indication missed its primary efficacy endpoint.

Wall Street wasn't too harsh, taking only $2.38, or 10.7 percent, of the firm's stock (NASDAQ:PDLI), leaving it to close Monday at $19.89.

Despite the setback, Jim Goff, senior director of corporate communications for the Fremont, Calif.-based company, told BioWorld Today the company firmly believes in the potential of daclizumab, a humanized antibody.

"We paid $80 million to reacquire rights to daclizumab in nontransplant indications, and we are very eager and anxious to continue its development in additional indications," he said. "Certainly we are disappointed in the results in ulcerative colitis, but as far as our focus in inflammatory bowel disease, we still have Nuvion, which we consider our lead product and our highest development priority."

Protein Design Labs (PDL) will continue evaluating daclizumab in asthma and multiple sclerosis, Goff said.

Daclizumab is sold by Hoffmann-La Roche Inc. in the U.S., Europe and other countries under the trade name Zenapax, for the prevention of acute rejection in kidney transplantation. Zenapax targets the interleukin-2 receptor on activated T cells. (PDL is unsure whether it will use the name Zenapax for potential indications.)

As part of an agreement reached between the firms in late September, PDL reacquired exclusive worldwide rights to daclizumab and is responsible for future development, manufacturing, and sales and marketing of the candidate outside transplantation. Roche will continue marketing Zenapax in transplantation until 2007, when PDL will be given the opportunity to repurchase those rights for about $21 million. If PDL does not buy the transplantation rights, it would pay royalties to Nutley, N.J.-based Roche on sales in all diseases other than transplantation. (See BioWorld Today, Oct. 1, 2003.)

The original collaboration dates back to 1989 when Roche acquired worldwide commercialization rights to Zenapax, which was then launched in the U.S. in 1997. Goff said Zenapax was the first humanized antibody to win marketing clearance in the U.S. (See BioWorld Today, Oct. 26, 1999.)

As for daclizumab in moderate or severe ulcerative colitis, PDL ran a 159-patient Phase II trial that was randomized, double blind and placebo controlled. Patients were randomized to receive either daclizumab at 1 mg/kg at a four-week interval for a total of two doses, or 2 mg/kg every two weeks for a total of four doses, or placebo. The primary study objectives were safety and achievement of remission, defined by the Mayo score. Patients eligible for entry into the trial had evidence of active ulcerative colitis at baseline, the company said.

Going forward, PDL expects to initiate a follow-on or additional Phase II study of daclizumab in asthma early next year. The firm might explore a subcutaneous dose, as well.

In March, PDL reported positive results from an initial study of the candidate in patients with chronic persistent asthma and with disease not well controlled by high doses of inhaled corticosteroid therapy.

The company said daclizumab was generally well tolerated and met its primary endpoint, which was a percent change in FEV1 from baseline to 12 weeks. Patients receiving daclizumab also demonstrated a statistically significant increase in the time to asthma exacerbation requiring oral corticosteroid rescue, as well as lower peripheral eosinophil counts. The Phase II randomized, double-blind, placebo-controlled trial was conducted at 24 centers in the U.S. and treated 114 patients.

Beyond asthma, Goff said work evaluating the candidate in multiple sclerosis also has produced encouraging results. The intention is to start a PDL-sponsored MS study in the first quarter of 2005.

Later this year, PDL expects to enter pivotal trials for Nuvion (visilizumab, anti-CD3) in inflammatory bowel disease.

PDL will host a webcast Wednesday to discuss results and development strategies for its programs in inflammatory bowel disease, including more detail on the results of the Phase II daclizumab study.