In February 2019 neuroscience drug development leaders from more than a dozen companies came together at the Marlowe Hotel in Cambridge, MA, with world-class academic clinicians from the Sean M. Healey & AMG Center for ALS at Mass General, the Healey Center science advisory council and the Northeast ALS Consortium (NEALS) to advance one of the most promising avenues for igniting a paradigm shift in ALS therapy development—the ALS platform trial.

A "platform trial" is a clinical trial with a single master protocol in which multiple treatments are evaluated simultaneously. Unlike traditional clinical trials, which study one treatment to answer one question, adaptive platform designs offer flexible features such as stopping a treatment arm early for efficacy, dropping treatments that don’t work, sharing control groups and adding in an accelerated manner new treatment arms. This approach is far more efficient and will yield information that can help all people with ALS. This is good news coming at the right time for patients with ALS.

There was palpable excitement in the room as the participants engaged in collaborative discussions surrounding their shared mission to accelerate the development of novel therapies and design more efficient and effective clinical trials for ALS. This endeavor was led by Merit Cudkowicz, MD, director of the Healey Center for ALS. The participants were excited about the next steps which will include meeting with people with ALS, ALS foundations and leadership at the Food and Drug Administration.

“The Healey Center has made it possible for top leaders to come together in a focused manner to create a groundbreaking platform trial program in ALS," said Dr. Cudkowicz. "This is a pivotal moment in time for ALS research. The approach, supported by our patients, the FDA, ALS clinicians and scientists and our pharma colleagues will accelerate the development of effective treatments. The trial platform approach will also significantly broaden access to novel treatments for our patients and facilitate the development of biomarkers, which can predict more quickly predict therapeutic success.”

Biostatisticians from Berry Consultants, a consulting company of renowned experts who specialize in adaptive platform trials, explained the advantages of platform trial approaches, using examples from other fields. They laid out an initial proposal for how to bring this to the ALS field, giving an excellent graphic depiction of how the statistics work in this new model.

Sabrina Paganoni, MD, PhD, a physician scientist at the Healey Center, gave a compelling illustration of how to design a platform trials in ALS. “These (adaptive platform) trials facilitate simultaneously studying multiple therapies for ALS and will yield a number of efficiency improvements,” said Dr. Paganoni. “In this new paradigm, more patients will have access promising therapies.”

“ALS trial endpoints have historically been based on function or survival,” said Jeremy Shefner, MD, PhD, from the Barrow Neurological Institute in Arizona. “There are many other endpoints to consider that can provide answers faster and possibly be measured in the home. Muscle strength and speech analysis are but a few of the other ways that we can measure the success of various drugs in a platform trial.”

Dr. Shefner noted that there are some exciting new ways to measure outcomes that are well into the development phase. This is very exciting news for patients and doctors alike.

Many of the workshop participants voiced the importance of shortening the interval of time from the time a patient enters a trial, to the time at which we know if the drug is successful or not. James Berry, MD, MPH, also from the Healey Center, discussed measuring response to therapy with specific fluid biomarkers.

“It is similar to the personalized medicine used in oncology” said Dr. Berry. “We want to move towards more targeted therapies in ALS.”

The timing for this approach could not be better. The pipeline of therapies for ALS is large, and we have the expertise and knowledge of how to do these important trials. Due to the transformative nature of the philanthropic gift from the Sean M. Healey and AMG, the Healey Center will provide initial support for this innovative platform trial program.

It is an exciting and hopeful time in the field of ALS, and the attendees in the room shared a common and burning desire to speed up the process to bring the great advances in understanding the biology of ALS to patients in well designed, efficient clinical trials.