Dr Francis CollinsFrancis S. Collins, MD, PhD
The National Institutes of Health (NIH) has announced that it is launching a new initiative aimed at encouraging innovation in amyotrophic lateral sclerosis (ALS) research. The program, dubbed Accelerating Leading-edge Science in ALS (ALS2), will invest $25 million over the course of a 5-year period.1

The Institutes noted that with no cure and a high rate of mortality associated with ALS, there is a vital need for advances. As of now, there are 2 therapies FDA-approved for its treatment— riluzole (Rilutek; Sanofi) and edaravone (Radicava; Mitsubishi Tanabe Pharma)—which can prolong the life of patients but cannot improve symptoms.

“Over the past few decades, there has been significant progress in our understanding of ALS, but we still do not have any breakthrough treatments for this terrible disease,” said Francis S. Collins, MD, PhD, director, NIH, said in a statement. “We hope this program will inject new ideas to the field to push us rapidly toward effective therapies.”

Part of the NIH Common Fund’s High-Risk, High-Reward (HRHR) research program, ALS2 is planned to support creative research deemed exceptional—and inherently riskier—in an attempt to “transform biomedical science,” the Institutes noted. Overall, the initiative is managed collaboratively by the NIH Common Fund, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Institute of Environmental Health Sciences, and the National Institute of General Medical Sciences.
 
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ALS2 will operate through the HRHR program’s Transformative Research Award initiative, which is considered well-suited for interdisciplinary science, in hopes of sparking new ideas.

The ALSprogram will use a 3-pronged approach, according to the NIH, which are as follows:
  • Adapt emerging tools and technologies from neuroscience and cell biology to identify what causes ALS at the molecular level, and how the disease progresses, leading to new therapeutic strategies.
  • Attract new talent from a range of scientific disciplines, including neuroscience, cell biology, bioengineering, genomics, chemistry, biophysics, environmental health sciences, and computational science.
  • Examine biological similarities between ALS and motor neuron disease in other neurodegenerative disorders, including frontotemporal dementia, chronic traumatic encephalopathy, Kennedy’s disease, spinal muscular atrophy, and primary lateral sclerosis.
This announcement follows a number of advances in ALS thus far this year, including Orphazyme’s arimoclomol getting fast track designation in June, and the FDA acceptance of an investigational new drug application—and a corresponding phase 3 study—for AB Science’s masitinib in April.2,3

As well, in an innovative fashion, a platform clinical trial with a novel design including a single master protocol and placebo control arm for multiple candidate treatments, successfully used to test new drugs for cancer, was launched in February at the Healey Center for ALS at Massachusetts General Hospital (MGH) to expedite clinical assessment of investigational agents for the terminal neuromuscular disease.4

In contrast to the more lengthy and costly process of conducting controlled clinical trials of 1 candidate drug at a time—which has yielded only 1 FDA-approved compound for ALS (edaravone) since riluzole was approved in 1995—the Healey Center announced in September 2019 that it would start with as many as 5 candidate drugs. The Healey Center is collaborating with the network of clinical research and treatment sites in the Northeast ALS Consortium (NEALS) and working with each of the selected biotechnology firms to tailor platform trial study arms to the respective investigational products.

The NIH noted that information on a Notice of Special Interest to accompany the Transformative Research Award funding opportunity will be posted at commonfund.nih.gov/tra/grants.
REFERENCES
1. NIH announces new Transformative Research Award program for ALS [press release]. Bethesda, MD. NIH. Published June 17, 2020. Accessed July 7, 2020. www.nih.gov/news-events/news-releases/nih-announces-new-transformative-research-award-program-als
2. Orphazyme’s arimoclomol receives US fast track designation in Amyotrophic Lateral Sclerosis [news release]. Copenhagen, Denmark: Orphazyme. Published May 22, 2020. Accessed June 1, 2020. globenewswire.com/news-release/2020/05/22/2037409/0/en/Orphazyme-s-arimoclomol-receives-US-Fast-Track-Designation-in-Amyotrophic-Lateral-Sclerosis.html
3. AB Science announces that FDA clears masitinib IND in Amyotrophic Lateral Sclerosis (ALS) allowing US patient enrollment to commence in phase 3 study [news release]. Paris, France. AB Science. Published March 31, 2020. Accessed April 3, 2020. globenewswire.com/news-release/2020/03/31/2009399/0/en/AB-Science-announces-that-FDA-clears-masitinib-IND-in-Amyotrophic-Lateral-Sclerosis-ALS-allowing-U-S-patient-enrollment-to-commence-in-Phase-3-study.html
4. Dunn A. First-of-its-kind trial in ALS spurs hope for brutal disease. Biopharmadive. September 25, 2019. Accessed July 7, 2020. biopharmadive.com/news/als-platform-trial-mass-general-healey-center/563595.