Alzheimer’s Drug Failure: Implications for Future R&D in Neuroscience
Alzheimer’s disease is a debilitating neurodegenerative disease characterized by dementia and memory loss. It is the sixth leading cause of death in the United States, where more than 5 million people are affected. There is clearly a need for more effective therapies that address this and other neurodegenerative diseases; however, the research and development (R&D) efforts put forth by pharmaceutical companies have rarely been successful, as illustrated by the recent failure of the Alzheimer’s drug bapineuzumab in clinical trials.
Johnson & Johnson and Pfizer in separate press releases on August 6, 2012, announced the discontinuation of their joint Phase III clinical development of intravenous (IV) bapineuzumab in mild-to-moderate cases of Alzheimer’s disease. This comes on the heels of disappointing results from the clinical trial Study 301, in which bapineuzumab was being tested in patients who are non-carriers of the ApoE4 (Apolipoprotein E epsilon 4) gene. Results indicated that bapineuzumab did not satisfy either cognitive or functional performance endpoints. These disappointing study results follow similar results announced on July 23 from Study 302, in which bapineuzumab also failed to meet clinical endpoints in ApoE4 carrier patients.
Bapineuzumab IV is an antibody that targets the beta-amyloid protein (A), which is believed to cause brain toxicity and is implicated in the pathology of Alzheimer’s disease. This immunotherapy approach is novel and is part of efforts to provide therapies that target the progression of Alzheimer’s disease as compared with existing therapies that are only palliative. Eli Lilly is also developing a similar drug, solanezumab, which is currently in Phase III clinical trials with results expected later this summer. Many scientists believe that for any therapy to be successful in impacting Alzheimer’s progression, it has to be started early, before damage to the brain has set in. Therefore, both bapineuzumab and solanezumab were already considered long-shots by many scientists and researchers because of the late stage of disease in the trials. However, limitations in diagnostic tools for Alzheimer’s make it difficult to make early diagnoses, and the search for biomarkers that will aid in this effort is an active area of research.
Many pharmaceutical companies already consider R&D in the neurosciences a highly risky proposition given the required capital investment. Results such as these for bapineuzumab will no doubt further this sentiment at a time when several major pharmaceutical companies have already strategically been pulling away from the neurosciences. Pfizer, GSK, AstraZeneca and Merck have all restructured or downsized their neuroscience research efforts, while Novartis recently shut down its neuroscience research facility in Basel, Switzerland. Pharmaceutical companies have opted to redirect their resources towards oncology where endpoints are clearer and drug approval is less difficult.
This trend of disappointing drug trials and the resultant disinvestment by pharmaceutical companies in neuroscience is a worrying trend that is further compounded by the fact that academic funding in the neurosciences has also been on the decline. In the UK, the Biotechnology and Biological Sciences Research Council plans to cut neuroscience funding by 20% in favor of other disciplines, while in the US budget concerns and the impending elections have created an uncertain outlook in overall federal research funding.
Neuroscience meanwhile remains one of the least understood areas of biology, and neurological disorders are considered by the World Health Organization (WHO) as one of the greatest threats to public health. It seems counterintuitive that given the global impact of neurological diseases, and the dearth of existing knowledge in the neurosciences, both academic and industry research in this field would be under threat. While one can acknowledge the challenges that neuroscience research presents, in an era of technological advancement, it doesn’t bode well for humanity that we would seemingly be walking away from a challenge that impacts the health of millions across the globe.
Rather than cut back on research in neuroscience, perhaps what is required is a paradigm shift, a change in focus towards newer models of drug discovery. Genetic-based approaches in neuroscience such as those adopted by GSK at its new sequencing center in Shanghai may prove more promising in future. We can only hope that this recent drug failure will not prove a further disincentive because for those in the pharmaceutical industry that maintain their efforts, particularly with neurodegenerative diseases such as Alzheimer’s, the market is only growing. A successful therapy would not only be immensely profitable but would reduce the ever-increasing global burden of Alzheimer’s disease.