Intellect Neurosciences Inc. (fka ILNS)

[montanus]

Alzheimer’s Disease Drug Development Deserves Special Government Incentives Including Market Exclusivity

Dec 13 2012
I was invited to speak about vaccines at the 6th Annual Alzheimer’s Drug Discovery Summit in Philadelphia. The meeting provided an excellent forum for a group of academic opinion leaders and industry specialists to hold in-depth discussions regarding recent developments and work being conducted internationally in the field. Unquestionably, 2012 has been an important year that generated critically important clinical data, including the results of the beta amyloid antibody Phase 3 trials and the studies conducted by the Dominantly Inherited Alzheimer’s Network (DIAN) that likely will have a significant impact on the design of future Alzheimer’s clinical trials. At the same time, the fact that the two major sets of Phase 3 clinical trials failed to meet their primary objectives underscored the enormous challenges that lie ahead, including the need to start treatments far earlier, likely when the first symptoms appear or perhaps several years before the onset of symptomatic disease.

The summit was organized by CBI in consultation with Marc Cantillon, MD, Wellness Managements LLC, and former Executive Director, Critical Path Institute Coalition Against Major Diseases (CAMD).

The first day of the conference was chaired by Johan Luthman, PhD, Senior Program Leader Neuroscience R&D, Franchise Integrator at Merck who also spoke about qualification of diagnostic and prognostic biomarkers for AD. Dr. Luthman emphasized the role of biomarkers as essential tools to support diagnosis of early stage AD, offering possibilities to detect prodromal, pre-dementia, stages of the disease and the potential to identify even presymptomatic patients at risk of developing the disease. In addition, Dr. Luthman described how in various natural progression studies, some biomarkers also have been shown to be good predictors of the clinical rate of disease progression (e.g. conversion to dementia), and explained how this link provides opportunities to allowing further stratification of trial populations, as well as evaluate novel therapeutics in populations that previously could not be entered into trials.

The opening address was by John C. Morris, MD, Friedman Distinguished Professor of Neurology, Director Knight Alzheimer’s Disease Research Center, Washington University School of Medicine. As Professor Morris explained, the initial publication of cross-sectional results from DIAN validate the use of Alzheimer’s biomarkers to identify preclinical AD as only mutant carriers demonstrated biomarker abnormalities. Although preliminary, the findings propose an instructive timeline for the pathophysiology of preclinical AD, beginning with elevated CSF Ab that presumably is present at birth but at perhaps 20-25 years prior to onset of symptomatic AD, begins to decline. The DIAN study will provide the infrastructure for randomized, placebo-controlled secondary prevention trials of mechanism-based therapies in dominantly inherited AD. Three drugs have been selected for an initial trial, including gantenerumab (Roche), a monoclonal antibody that binds to all forms of aggregated beta amyloid and currently in prodromal Phase 2/3 trials; solanezumab (Eli Lilly & Co), a monoclonal antibody that binds to soluble forms of beta amyloid, which is to be tested in additional Phase 3 trials; and a BACE inhibitor from Eli Lilly that targets beta amyloid, theoretically reducing the production of beta amyloid and slowing the accumulation of plaques in the brain. Although dominantly inherited AD occurs in only about 1 percent of the population, most experts believe the lessons learned from these trials will have widespread utility and may be applied to testing therapeutics in a much broader population.

J. Michael Ryan, MD, Vice President and Head Neurodegeneration Clinical Science Unit at Novartis moderated a Roundtable Discussion starting with his personal perspective of how recent results will reshape the design and conduct of future AD clinical trials, as well as the allocation of resources devoted to Alzheimer’s research. Dr. Ryan highlighted what had been a recurring theme throughout the conference regarding how the industry will address the major challenges ahead.

I had recommended the organizers of the conference invite John Reppas MD, PhD, Director of Policy at the Neurotechnology Industry Organization (NIO), a global trade association representing companies involved in commercial neurosciences, brain research institutes and patient advocacy groups.

In his address, Dr. Reppas outlined federal policy levers to foster innovation and address public health in AD, especially focused on the NIO-sponsored Neurodegenerative Drug Incentive Initiative, which aims to address the widening gap between prevalence and treatment in neurodegenerative disease conditions, such as AD, Parkinson’s and others that are causing massive public health and economic burdens. Dr. Reppas said the prospects for advancing new therapies to practice are imperiled by the unique length and expense of clinical trials needed to demonstrate safety and efficacy in these diseases. Because of the slowly progressing nature of neurodegenerative diseases, the additional development time consumes both patent protection and defers market entry. It also has led many investors and developers to abandon disease-modifying approaches entirely.

I fully concur with NIO’s belief that the solution to this problem lies in creating a new market exclusivity for sponsors of novel disease-modifying therapeutics that are targeted to neurodegenerative disease, especially AD. The rationale of the NIO initiative follows that of the 1983 Orphan Drug Act, which has since spurred development of new medicines for hundreds of orphan diseases that, otherwise, would not have been addressable given the small market size. A guaranteed market exclusivity period of ten years would be sufficient to tilt the cost-benefit consideration toward continuing drug development for neurodegenerative diseases.

Much has been made about the recent decision of the Obama Administration to push for a $156 million increase in funding for Alzheimer's research over the next two years. Its proponents, especially the Alzheimer’s Association, should be lauded for their commitment to the cause. However, the size of the award is just a drop in the bucket that, in my opinion, will do very little, if anything, to alleviate the situation. Sadly, it underscores a gross lack of understanding on Capitol Hill regarding the needs of the research community -- including industry -- to identify new drugs and advance them through clinical trials as the only way to prevent a catastrophic socio-economic disaster, as more and more Americans are affected by this disease. One wonders how those government officials involved in this decision would feel about the impact of allocating similar funds, barely sufficient to purchase a single stealth bomber, to the overall security of the nation.

I would urge all to support the NIO initiative.

--Daniel Chain, Chairman and CEO, Intellect Neurosciences, Inc.

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