NEW BRUNSWICK, N.J. and NEW YORK—After themuch-watched intravenous drug bapineuzumab for mild-to-moderate Alzheimer'sdisease 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 ImmunotherapyProgram (AIP) of Janssen Alzheimer Immunotherapy and Pfizer, an equalcollaboration committed to researching and developing selective products forthe treatment and/or prevention of neurodegenerative conditions, includingAlzheimer'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 theApoE4 (apolipoprotein E epsilon 4) genotype and the patients in the other trialdid.
The two co-primary clinical endpoints of the PhaseIII trials were change in the Alzheimer's Disease Assessment Scale-Cognitivesubscale (ADAS-Cog), a validated measure of cognition, and the DisabilityAssessment for Dementia (DAD), a validated instrument to measure function. Bothendpoints failed to show any significant difference compared to the use of aplacebo.
The Janssen and Pfizer joint steering committeefor the AIP has decided to discontinue all other bapineuzumab IV studies inpatients with mild-to-moderate Alzheimer's disease, which includes not only twoPfizer-led Phase III studies (Study 3000 and Study 3001) but also all follow-onextension studies in patients with mild-to-moderate Alzheimer's diseasereceiving bapineuzumab IV. All patients in the discontinued studies will have afollow-up evaluation and the alliance will conduct final data analyses, Pfizerreports.
Bapineuzumab IV is an antibody that targetsbeta-amyloid (Aβ), a protein that can exert toxic effects in the brain and isbelieved to play a central role in the pathology of Alzheimer's disease.
In relation to this discontinuation of bapineuzumabIV, J&J says that it expects to record an after-tax, non-cash special itemrelated to in-process research and development consisting of a net charge toearnings of between $300 million and $400 million in the third quarter of 2012.
"While we are disappointed in the results of thetwo bapineuzumab IV studies, particularly in light of the urgent need for newadvancements in Alzheimer's disease, we believe that targeting and clearingbeta amyloid remains a promising path to potential clinical benefits for peoplesuffering from this disease," said Dr. Husseini K. Manji, global therapeuticarea head for neuroscience at Janssen Research & Development LLC. "Janssenremains strongly committed to tackling the enormous unmet medical needs inAlzheimer's disease. We believe the trial results will provide a rich data setthat will advance our understanding of this complex disease and inform futureresearch in this field. Studies with other compounds in earlier stages ofdevelopment in the AIP portfolio are continuing and future development strategieswill be discussed jointly by the alliance partners."
"We are obviously very disappointed in theoutcomes of this trial. We are also saddened by the lost opportunity to providea meaningful advance for patients afflicted with mild-to-moderate Alzheimer'sdisease and their caregivers," echoed Dr. Steven J. Romano, senior vicepresident and head of the Medicines Development Group, Global Primary CareBusiness Unit, Pfizer Inc. "Yet these data, and the subgroup and biomarkeranalyses underway, will further inform our understanding of this complexdisease and advance research in this field."
While there was hope and hype around bapineuzumab,analysts like Damien Conover of Morningstar and Anthony Butler of BarclaysCapital point out that most investors didn't have high expectations for thedrug's success, but there is a sense of emotional disappointment nonethelessbecause of the impact of Alzheimer's disease and desires for a cure.
