The data are from the second pivotal phase 3 clinical trial of the investigational drug methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illnesses, such as cancer and cardiovascular disease. Results presented at DDW showed that nearly half of constipated patients with advanced illness experienced laxation (bowel movement) within four hours of receiving their first dose of methylnaltrexone (0.15 mg/kg), and more than 70% responded by the end of the first week of treatment (0.15 mg/kg qod). For those who responded, the median time to laxation following methylnaltrexone treatment was 30 minutes, and there were no reports of diminished analgesia due to study medication.
"In order to provide the most compassionate care possible, health care professionals want to focus on aggressive pain management without the worry of opioid-induced bowel dysfunction," says study investigator Neil Slatkin, M.D., DABPN, Director, Department of Supportive Care, Pain and Palliative Medicine, City of Hope, Duarte, CA. "These data are encouraging for patients living with advanced illnesses who must take opioids to control their pain."
Opioids such as morphine are widely used to lessen the suffering of the approximately 1.7 million Americans living with painful terminal illnesses. In addition to their analgesic effect of blocking the perception of pain within the central nervous system, these medications also interact with opioid-specific receptors outside the brain and spinal cord, resulting in constipation. More than 50 percent of cancer patients admitted to palliative care units experience opioid-induced bowel dysfunction. Opioid-induced bowel dysfunction includes constipation that is not adequately addressed by current therapies, such as laxatives or stool softeners. Methylnaltrexone is a peripheral opioid-receptor antagonist designed to rapidly block the effect of these medications on opioid receptors outside the central nervous system. Since methylnaltrexone does not cross the blood-brain barrier, it does not interfere with brain-centered pain relief.
Study Design
In the double blind, placebo-controlled trial, 133 patients with advanced illness at nursing homes, hospice and palliative care centers across the U.S. were randomized to receive either methylnaltrexone (0.15 mg/kg, SC) or placebo every other day for two weeks. All patients experienced opioid-induced constipation, despite the use of laxatives and stool softeners. No rescue laxatives were allowed within four hours of dosing. By day eight, a blinded dose escalation was permitted (methylnaltrexone, 0.30 mg/kg or placebo) if a patient did not have at least three bowel movements during the previous week that were not associated with rescue therapy. This dosing regimen was continued through the remaining week of the trial (dosing on days 9, 11 and 13). Co-primary endpoints were laxation within four hours of the first dose and laxations occurring within four hours of at least two of the first four doses.
Top-line Results
- 48.4% of patients experienced laxation within 4 hours of receiving the first dose of methylnaltrexone (0.15 mg/kg), more than three times the rate seen in patients treated with placebo (15.5%) (P<0.0001).
- 51.6% of patients experienced laxation within four hours of receiving at least two of the first four doses, compared to 8.5% receiving placebo (P<0.0001).
- The most frequently reported adverse event was transient abdominal cramping.
Contacts: Wyeth
Media Contacts:
Gerald Burr
Wyeth Pharmaceuticals
(484) 865-5138
Doug Petkus
Wyeth
973-660-5218
Investor Contact:
Justin Victoria
Wyeth
(973) 660-5340
Progenics Pharmaceuticals, Inc.:
Richard W. Krawiec, Ph.D.
Vice President
Corporate Affairs
(914) 789-2800
rkrawiec@progenics.com
Progenics-Wyeth Collaboration
Under the terms of the collaboration, Wyeth will develop oral methylnaltrexone worldwide. Progenics will lead the U.S. development of subcutaneous and intravenous methylnaltrexone, while Wyeth will lead development for these formulations outside of the U.S. In 2006, phase 3 clinical studies are set to begin in the U.S. and Europe for post-operative bowel dysfunction with intravenous methylnaltrexone, and the oral product will enter phase 2 in patients receiving opioids for chronic pain.
About Progenics
In December 2005, Wyeth and Progenics entered into a license and co-development agreement for the development and commercialization of methylnaltrexone. Progenics Pharmaceuticals, Inc., of Tarrytown, NY, is a biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. Principal programs are directed toward symptom management and supportive care and the treatment of HIV infection and cancer. The Company has four product candidates in clinical development and several others in preclinical development. The Company, in collaboration with Wyeth, is developing methylnaltrexone for the treatment of opioid-induced side effects, including constipation and post-operative bowel dysfunction. In the area of HIV infection, the Company is developing the viral-entry inhibitor PRO 140, a humanized monoclonal antibody targeting the HIV coreceptor CCR5 (in phase 1b studies). In addition, the Company is conducting research on ProVax, a novel prophylactic HIV vaccine. The Company is developing in vivo immuno¬therapies for prostate cancer, including a human monoclonal antibody directed against prostate-specific membrane antigen (PSMA), a protein found on the surface of prostate cancer cells. Progenics is also developing vaccines designed to stimulate an immune response to PSMA. A recombinant PSMA vaccine is in phase 1 clinical testing. The Company is also developing a cancer vaccine, GMK, in phase 3 clinical trials for the treatment of malignant melanoma.
PROGENICS DISCLOSURE NOTICE The information contained in this document is current as of May 23, 2006. This press release contains forward-looking statements. Any statements contained herein that are not statements of historical fact may be forward-looking statements. When the Company uses the words "anticipates"' "plans"' "expects" and similar expressions, it is identifying forward-looking statements. Such forward-looking statements involve risks and uncertainties which may cause the Company's actual results, performance or achievements to be materially different from those expressed or implied by forward-looking statements. Such factors include, among others, the uncertainties associated with product development, the risk that clinical trials will not commence or proceed as planned, the risks and uncertainties associated with dependence upon the actions of our corporate, academic and other collaborators and of government regulatory agencies, the risk that our licenses to intellectual property may be terminated because of our failure to have satisfied performance milestones, the risk that products that appear promising in early clinical trials do not demonstrate efficacy in larger-scale clinical trials, the risk that we may not be able to manufacture commercial quantities of our products, the uncertainty of future profitability and other factors set forth more fully in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2005, and other reports filed with the Securities and Exchange Commission, to which investors are referred for further information. In particular, the Company cannot assure you that any of its programs will result in a commercial product.
Progenics does not have a policy of updating or revising forward-looking statements and assumes no obligation to update any forward-looking statements contained in this document as a result of new information or future events or developments. Thus, it should not be assumed that the Company's silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements.
About Wyeth
Wyeth is one of the world's largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products and nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health.
WYETH DISCLOSURE NOTICE: The statements in this press release that are not historical facts are forward-looking statements based on current expectations of future events and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include risks associated with the inherent uncertainty of the timing and success of product research, development and commercialization (including with respect to our pipeline products), drug pricing and payment for our products by government and third party-payors, manufacturing, data generated on the safety and efficacy of our products, economic conditions including interest and currency exchange rate fluctuations, changes in generally accepted accounting principles, the impact of competitive or generic products, trade buying patterns, global business operations, product liability and other types of litigation, the impact of legislation and regulatory compliance, intellectual property rights, strategic relationships with third parties, environmental liabilities, and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption "Item 1A, Risk Factors." We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.