Applied Clinical Trials
Pharma and diagnostics companies need to strengthen alignment in Alzheimer’s disease research-to help turn science and data into actionable medical innovations.
Edward I. Ginns
Since the turn of the decade, pharmaceutical and diagnostic companies have collaborated more than ever before to advance the commercial and clinical value of precision medicine. Today, the need for these collaborations is greater than ever before, as healthcare tackles one of medicine’s greatest challenges: Alzheimer’s disease (AD). According to the Alzheimer’s Association, more than 5.7 million Americans live with AD, and the number is projected to increase to 14 million by the year 2050.
Tragically, AD remains virtually untreatable. Currently available medications have limited impact on progression and virtually no impact on the disease’s severity.
Several barriers have stymied successful research and commercialization of drug targets. In fact, despite a drug pipeline with more than 100 treatment agents, not one drug has been approved to treat the underlying cause or slow the progression of AD since 2003. A 2018 analysis of Alzheimer’s drug development published in Translational Research & Clinical Interventions noted that eight agents listed in Phase III in 2017 failed in clinical trials. Six drugs listed in Phase II last year are no longer in development, and trials for five particular agents in Phase I in 2017 were either completed or terminated and are not listed in the 2018 pipeline.
However, recent announcements from regulatory bodies and public health organizations offer great hope that promising new therapies can be accelerated through trials and approvals to the point of clinical care.
In April, the National Institute on Aging and Alzheimer’s Association (NIA-AA) released a new research framework that proposes the use of biomarkers to assess the presence of AD, whether symptoms are present or not.
While not currently intended by clinical use, this new framework is expected to build upon research discoveries that certain biomarkers are predictive of AD by as much as 20 years. Specifically, the NIA-AA “biological construct” proposes to use three general groups of biomarkers-beta-amyloid, tau, and neurodegeneration, or neuronal injury (AT(N))-in a new AD classification system that covers the continuum of the disease.
The NIA-AA framework comes on the heels of the FDA’s draft guidance in February on using biomarkers in an approval pathway for new AD drugs if drug developers could hit acceptable biomarkers that indicate the drug is working.
Taken together, these developments could lead to an improved understanding of the disease process and the sequence of events that lead to cognitive impairment and dementia-and an entirely new way of accurately measuring clinically meaningful cognitive and functional outcomes based on biological data. Most of all, they hold the potential to advance AD drug R&D and potentially surmount the many barriers to success in this area.
But the use of biomarkers in AD research will also require new types of collaborations by pharmaceutical companies and R&D partners-including diagnostic providers. While the new framework does not recommend the use of current biomarkers for clinical applications, some specialists today order them as clinical tests to enhance their assessment of patients. As a result, diagnostic providers specializing in AD, cognitive impairment, and dementia likely already perform these biomarker tests and may have vast data sources on which to glean insights useful in research settings.
AD drug research is a long-term game. In order to minimize risk and optimize a smooth and successful transition from lab discovery to clinical trial to regulatory approval, pharma and diagnostic companies should design a long-term strategy to turn science and data into actionable medical innovations. These include, potentially, companion and complementary diagnostics for future AD therapies. Here, a diagnostic provider can help generate the right data to support regulatory approval and payer support post-market launch.
Edward I. Ginns, MD, PhD, Medical Director of Neurology, Quest Diagnostics