Replies to post #1493 on Biotech Values

[DewDiligence]

Re: Asthma competition and trial design:

Asthma is a highly-competitive market and is getting more so. This is one reason I have valued GENR’s share of the IL-9 program at only $80M on a present-value basis (#msg-1981262)

>> After a run-in period to verify dependence on inhaled corticosteroids, patients were randomized to receive daclizumab or placebo in a 3:1 ratio. <<

I like PDLI’s use of a “run in” period to filter out “bad” patients before randomizing the remaining patients to one of the two trial arms (active drug or placebo). I think this design should be used more often in disease settings where patients are likely to experience a strong placebo effect (e.g. CNS illnesses) or spontaneous improvement (e.g. respiratory diseases).

AMD is a disease where a “run in” period is probably not appropriate because patients rarely if ever improve without treatment and there is a clear-cut efficacy measure (visual acuity on the eye chart), which makes a strong placebo effect unlikely.

[DewDiligence]

PDLI’s asthma drug fails in ulcerative colitis:

[Program in asthma will continue.]

http://biz.yahoo.com/prnews/040516/sfsu001_1.html

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Protein Design Labs Reports Negative Results in Phase II Clinical Trial of Daclizumab in Ulcerative Colitis

Sunday May 16, 12:00 pm ET

Study Finds no Clinical Activity; Further Development to Focus on Asthma and Multiple Sclerosis

FREMONT, Calif., May 16 /PRNewswire-FirstCall/ -- Protein Design Labs, Inc. (Nasdaq: PDLI; PDL) today reported that its humanized antibody, daclizumab, did not meet the primary endpoint in a Phase II clinical trial in patients with moderate or severe ulcerative colitis. The primary efficacy endpoint in the study, the proportion of patients who achieved remission at week eight, did not meet statistical significance at either of the dose levels tested. Treatment with daclizumab antibody product was well tolerated.

Steven Benner, M.D., Senior Vice President and Chief Medical Officer, PDL, said, "We are disappointed that daclizumab did not demonstrate a clinical benefit in this setting. Based on these findings, we do not plan to further develop daclizumab as a treatment for ulcerative colitis.

"We remain firmly committed to the development of novel therapies in inflammatory bowel disease with the ongoing development of our Nuvion® antibody product for the potential treatment of patients with severe ulcerative colitis who failed to respond to treatment with intravenous steroids," Dr. Benner continued. "Based on recent encouraging Phase I results, as well as potential time to market, we continue to view Nuvion as our highest priority program.

"We are also committed to further development of daclizumab in additional indications, with top priority now in patients with chronic, persistent asthma," Dr. Benner added. "Our current plan is to follow the positive Phase II data in this setting reported earlier this year with a follow-on study. As the second priority for daclizumab, we also continue preparatory work for a PDL clinical trial in patients with multiple sclerosis. Our current plans are to initiate a follow-on study in each of asthma and multiple sclerosis by the first quarter of 2005."
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[DewDiligence]

PDLI inks worldwide partnership with Roche for Zenapax in asthma:

[Roche has come full circle on Zenapax (a.k.a. Daclizumab). Roche once owned the drug outright but sold the rights to PDLI; now, apparently liking the phase-2 asthma data (#msg-2604857), Roche wants back in.]

http://biz.yahoo.com/prnews/040916/sfth034_1.html

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Roche and Protein Design Labs to Jointly Develop Zenapax(R) for Asthma

Thursday September 16, 1:30 am ET

NUTLEY, N.J. and FREMONT, Calif., Sept. 16 /PRNewswire-FirstCall/ -- Roche and Protein Design Labs (PDL) (Nasdaq: PDLI - News) today announced a worldwide agreement to co-develop and commercialize Zenapax® (daclizumab) for asthma and related respiratory diseases, based on recent positive phase II data in patients with moderate to severe asthma.

Mark McDade, Chief Executive Officer, PDL, said, "The continued development of daclizumab in asthma is among PDL's highest clinical development priorities. With Roche as our ongoing partner in this indication, we believe daclizumab will obtain the resources needed to develop the full potential of this humanized antibody in asthma."

"This new agreement will strengthen our pipeline in asthma, where we are currently in phase II development of a novel oral treatment," said William Burns, Global Head of Roche's Pharmaceuticals Division. "We believe that daclizumab will offer patients a significant improvement over today's current therapy. Our long-standing relationship with PDL continues to grow as we develop daclizumab further."

Under terms of the agreement, PDL will receive a $17.5 million upfront payment as well as up to $187.5 million in development and commercialization milestones for successful further development of daclizumab. Roche and PDL will globally co-develop daclizumab in asthma, share development expenses and co-promote the product in the US. Outside the US, PDL will receive royalties on net sales of the product in asthma.

About the Roche - PDL partnership

In 1989, Roche acquired the worldwide rights to daclizumab, a product that has since gained an important position within Roche's transplantation portfolio. In October 2003, Roche resold to PDL all rights to daclizumab, except in transplantation, until 2007 when PDL will have the option to re-acquire the transplantation rights as well. In 2004, PDL approached Roche with compelling phase II data for daclizumab in asthma, leading to today's announcement for the continued co-development of daclizumab in respiratory disorders by Roche and PDL.

About Asthma

Asthma is among the most common chronic medical conditions in the United States and worldwide, affecting more than 20 million people in the United States, according to the American Lung Association (ALA) and the American Academy of Allergy, Asthma & Immunology (AAAAI). According to a recent report on the global burden of asthma published by the NIH, WHO and the Global Initiative for Asthma, asthma is one of the most common chronic diseases in the world and it is estimated that around 300 million people in the world currently have asthma. The rate of asthma continues to increase and it is estimated that there may be an additional 100 million persons suffering from asthma by 2025. Asthma accounts for 1 in every 250 deaths worldwide.

About Zenapax

Zenapax is an immunosuppressive humanized monoclonal antibody or "anti-rejection" drug approved by the FDA in December 1997 to be used in combination with other immunosuppressive drugs (cyclosporine and corticosteroids) to prevent acute organ rejection in kidney transplant patients. The recommended dose of Zenapax is 1.0 mg/kg. Based on clinical trials, the standard course of Zenapax therapy is five doses.

The most frequently reported adverse events associated with Zenapax were constipation, nausea, diarrhea and vomiting. Cellulitis and wound infections occurred more frequently in patients treated with Zenapax versus placebo. Severe hypersensitivity reactions following Zenapax administration have been reported rarely.

Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Zenapax. The physician responsible for Zenapax administration should have complete information requisite for the follow-up of the patient. Zenapax should be administered only by healthcare personnel trained in the administration of the drug who have available adequate laboratory and supportive medical resources.

About Protein Design Labs

In October 2003, PDL acquired all rights to Zenapax®, excluding transplantation indications but with the option to gain such indication rights by 2007. PDL retains this right in accordance with the terms of the October 2003 agreement.

Protein Design Labs is a leader in the development of humanized antibodies to prevent or treat various disease conditions. PDL currently has antibodies under development for autoimmune and inflammatory conditions, asthma and cancer. PDL holds fundamental patents for its antibody humanization technology. Further information on PDL is available at www.pdl.com.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world's leaders in pharmaceuticals and diagnostics. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company's areas of therapeutic interest are: dermatology; genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.
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