Alzheimer’s Drug Development Comparable To Cancer 50 Years Ago, Says Targacept CEO
This article was originally published in The Pink Sheet Daily
Executive Summary
Biomarkers and diagnostic tools must be developed to allow drug manufacturers to target Alzheimer’s disease modification, BioInvestor Forum panelists say.
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Developing drugs to effectively treat Alzheimer's disease has been stymied by a failure to understand underlying causes of the disease, according to industry panelists at the BioInvestor Forum in San Francisco. Four FDA-approved Alzheimer's drugs are on the market; three acetylcholinesterase inhibitors Pfizer/Eisai's Aricept (donepezil), Novartis' Exelon (rivastigmine), and Johnson & Johnson's Razadyne (galantamine, formerly Reminyl )); and Forest Labs' N-methyl-D-aspartate antagonist Namenda (memantine). But "the unmet need in Alzheimer's disease is tremendous," Targacept CEO Donald deBethizy said Oct. 19. There is "an incredible lack of efficacy in these acetylcholinesterase inhibitors," he added, noting that the U.K. National Institute for Health & Clinical Excellence has said that acetylcholinesterase inhibitors are not cost-effective for patients with less severe forms of the disease (1 (Also see "NICE To Release Final Alzheimer's Guidance Nov. 22" - Pink Sheet, 11 Oct, 2006.)). Acetylcholinesterase inhibitors also have gastrointestinal side effects, which limit dosing options, panelists noted. "It's like 50 years ago with cancer, we are still learning about the underlying mechanisms" of the disease, deBethizy said. "Nobody has decided how to assess disease modification." "We hope to get into the market with a symptomatic improvement claim...and then go after disease modification, because we hope by then people will understand that better." Targacept, based in Winston-Salem, N.C., has inked a deal with AstraZeneca to develop and commercialize its Phase II Alzheimer's candidate TC-1734, an oral neuronal nicotinic receptor (2 (Also see "AstraZeneca Licenses Nicotinic Alzheimer’s Treatment From Targacept" - Pink Sheet, 28 Dec, 2005.)). Disease modification claims would also require longer studies, more suitable to Phase IV, Ceregene CEO Jeffrey Ostrove said. It is only in Phase IV where "you are following large number of patients for four, five, six, seven years, that you could make those claims." San Diego-based Ceregene is developing the nerve growth factor CERE-110 in Phase I for Alzheimer's. The gene therapy is administered to the brain via stereotactic injection. Ultimately, like oncology, advances in Alzheimer's therapy probably will depend on development of tools to identify early signs of the disease, University of California-San Francisco Assistant Professor Adam Boxer told meeting attendees. "Any advance that we have in the therapeutic domain will rely on [the development] of good biomarkers," Boxer said. Without adequate biomarkers, manufacturers cannot identify early stage patients for research and clinical trials, panelists said. By focusing on later-stage, identifiable patients, manufacturers are forced to concentrate on drug targets for symptomatic improvement and progression delay, rather than disease modification. "Pfizer is very interested in the diagnosis and diagnostic tools, as well as biomarkers" for Alzheimer's, Pfizer/Rinat Neuroscience Senior Director-Strategic Alliances Paul Resnick said. "You don't want to wait two years to know whether your drug is working." Rinat has monoclonal antibody RN1219 in Phase I for Alzheimer's. Pfizer acquired South San Francisco-based Rinat in April. In a same-day presentation, San Francisco biotech Medivation released promising Phase II data for its Alzheimer's drug Dimebon . The oral neuroprotectant drug met all five efficacy endpoints in a six-month randomized, double-blinded, placebo-controlled trial of 183 patients in Russia with mild to moderate Alzheimer's disease. Patients' cognition and memory functions improved over baseline through week 26, Medivation CEO David Hung told BioInvestor Forum attendees. "We think that's significant because if you look at Aricept's effects on cognition and memory...at week 24, there's a negative slope," he said. Dimebon, which has been approved in Russia since 1983 for use in allergies, also is in Phase I for Huntington's disease. - Joshua Berlin ([email protected]) |