Partners Elan Corp. plc and Wyeth said they plan to begin Phase III testing of their lead immunotherapeutic candidate bapineuzumab (AAB-001) for mild to moderate Alzheimer's disease in the second half of this year, boosting excitement around the disease-modifying agent.
Company officials declined to comment beyond a joint press release that said the decision to advance the program reflects findings from a scheduled interim look at an ongoing Phase II study, which remains blinded, as well as the totality of what they've learned from their immunotherapy programs and the severity of the disease. Reading between the lines, there's clearly an assumption of good enough Phase II data, though the partners stressed that no conclusion about the study can be drawn until it's complete and final data are analyzed and released next year.
But all signals certainly appear positive.
"This looks like a real program," said Ian Sanderson, an analyst with Cowen and Co. "There have been lots of rumors that Wyeth would terminate the program, so this relieves a lot of the rumor overhang."
Elan's shares (NYSE:ELN) traded up $2.09 on Monday, or 12.6 percent, to $18.69.
Sanderson told BioWorld Today that the announcement isn't necessarily indicative of moving the product's potential approval ahead of schedule, noting that he's forecasted the partners to file with the FDA in the second half of 2009 and receive a decision in 2010. The companies have not disclosed such schedules, but given bapineuzumab's fast-track status, it might also qualify for a six-month review when Elan and Wyeth submit their application.
The humanized monoclonal antibody "provides a mechanism for which beta-amyloid is cleared from the brain," Sanderson said, by halting the formation of new plaques and possibly removing existing plaques. That would make it a disease-modifying agent like no other in development, assuming the belief that the buildup of beta-amyloid plaques does indeed drive Alzheimer's.
In contrast, Sanderson said two other late-stage drugs in development for the disease, Flurizan (tarenflurbil, from Myriad Genetics Inc.) and Alzhemed (tramiprosate, from Neurochem Inc.), "are much less potent and much less direct in their mechanism."
The randomized, double-blinded, placebo-controlled, multiple-ascending dose study into which the partners peered is to include nearly 240 patients with mild to moderate Alzheimer's, divided into four cohorts. Its primary objective is to measure bapineuzumab's safety, while secondary assessments of cognitive and functional status include evaluations of the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), the Neuropsychological Test Battery (NTB) and the Disability Assessment for Dementia (DAD) scale to measures quality of life. Each patient's participation lasts about 18 months.
It would serve as one of two studies for registration, along with the coming Phase III trial. That study's design has yet to be finalized with regulatory agencies, so the partners declined to share any details on their plans for the protocol. Sanderson speculated that it would evaluate a narrower dose range than Phase II and also include patients with the ApoE4 allele, which seems to provide a genetic predisposition to bapineuzumab response.
In addition, he said the companies would do well to convince the FDA that less rigorous patient monitoring is needed than Phase II, in which they had MRI scans after each infusion, every 12 weeks. "It's very burdensome on the patients and caregivers," he said.
A second Phase II trial is currently being conducted in Europe to evaluate patients' beta-amyloid levels through imaging. The companies do not expect that any data from the two trials to be publicly available until both are complete next year.
Elan, of Dublin, Ireland, and Wyeth, of Madison, N.J., are working in a 50:50 collaboration to research, develop and commercialize bapineuzumab and other immunotherapeutic approaches to treat mild to moderate Alzheimer's, and possibly to prevent the onset of the disease. In addition to bapineuzumab, other programs in their collaborative effort include a subcutaneous formulation of AAB-001, ACC-001 and AAB-002. The partners equally share all costs in the arrangement, and would split any revenues that arise down the road.
Drugs currently indicated for Alzheimer's include Aricept (donepezil, from Pfizer Inc.), Exelon (rivastigmine, from Novartis AG), Cognex (tacrine, from First Horizon Pharmaceutical Corp.), Reminyl (galantamine, from Shire Pharmaceuticals Group plc) and Namenda (memantine, from Forest Laboratories Inc.). All treat disease symptoms, such as slowing patients' declining cognition, but generally they "just buy a little time," Sanderson said.