Alzheimer’s drug gets boot by Pfizer and Johnson & Johnson after Phase III program failure
NEW BRUNSWICK, N.J. and NEW YORK—After the much-watched intravenous drug bapineuzumab for mild-to-moderate Alzheimer’s disease failed to meet clinical endpoints in a pair of Phase III trials led by Johnson & Johnson subsidiary Janssen Alzheimer Immunotherapy, J&J and Pfizer Inc. have announced the discontinuation of further development of the agent.
The drug was part of the Alzheimer's Immunotherapy Program (AIP) of Janssen Alzheimer Immunotherapy and Pfizer, an equal collaboration committed to researching and developing selective products for the treatment and/or prevention of neurodegenerative conditions, including Alzheimer’s disease.
The Janssen-led trials (Study 301 and Study 302) differed from each other in that the patients in one trials did not carry the ApoE4 (apolipoprotein E epsilon 4) genotype and the patients in the other trial did.
The two co-primary clinical endpoints of the Phase III trials were change in the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), a validated measure of cognition, and the Disability Assessment for Dementia (DAD), a validated instrument to measure function. Both endpoints failed to show any significant difference compared to the use of a placebo.
The Janssen and Pfizer joint steering committee for the AIP has decided to discontinue all other bapineuzumab IV studies in patients with mild-to-moderate Alzheimer’s disease, which includes not only two Pfizer-led Phase III studies (Study 3000 and Study 3001) but also all follow-on extension studies in patients with mild-to-moderate Alzheimer’s disease receiving bapineuzumab IV. All patients in the discontinued studies will have a follow-up evaluation and the alliance will conduct final data analyses, Pfizer reports.
Bapineuzumab IV is an antibody that targets beta-amyloid (Aβ), a protein that can exert toxic effects in the brain and is believed to play a central role in the pathology of Alzheimer’s disease.
In relation to this discontinuation of bapineuzumab IV, J&J says that it expects to record an after-tax, non-cash special item related to in-process research and development consisting of a net charge to earnings of between $300 million and $400 million in the third quarter of 2012.
“While we are disappointed in the results of the two bapineuzumab IV studies, particularly in light of the urgent need for new advancements in Alzheimer’s disease, we believe that targeting and clearing beta amyloid remains a promising path to potential clinical benefits for people suffering from this disease,” said Dr. Husseini K. Manji, global therapeutic area head for neuroscience at Janssen Research & Development LLC. “Janssen remains strongly committed to tackling the enormous unmet medical needs in Alzheimer’s disease. We believe the trial results will provide a rich data set that will advance our understanding of this complex disease and inform future research in this field. Studies with other compounds in earlier stages of development in the AIP portfolio are continuing and future development strategies will be discussed jointly by the alliance partners.”
“We are obviously very disappointed in the outcomes of this trial. We are also saddened by the lost opportunity to provide a meaningful advance for patients afflicted with mild-to-moderate Alzheimer’s disease and their caregivers,” echoed Dr. Steven J. Romano, senior vice president and head of the Medicines Development Group, Global Primary Care Business Unit, Pfizer Inc. “Yet these data, and the subgroup and biomarker analyses underway, will further inform our understanding of this complex disease and advance research in this field.”
While there was hope and hype around bapineuzumab, analysts like Damien Conover of Morningstar and Anthony Butler of Barclays Capital point out that most investors didn’t have high expectations for the drug’s success, but there is a sense of emotional disappointment nonetheless because of the impact of Alzheimer’s disease and desires for a cure.