How the Healey ALS Platform Trial is Helping to Accelerate the Pathway to New ALS Treatments

Sabrina Paganoni, MD, PhD, co-director of the Neurological Clinical Research Institute at Massachusetts General Hospital and associate professor of Physical Medicine and Rehabilitation at Harvard Medical School, speaks about her work on the HEALEY ALS Platform Trial, a novel approach that could help identify effective treatments faster for patients, and the implications of platform trials for the future of clinical research.

Current treatment options for amyotrophic lateral sclerosis (ALS), a life-threatening, neurogenerative disease, are limited. Previous research in this field has been challenged by the steep cost and complexity of clinical trials, and the quick progression of the disease in patients.

Sabrina Paganoni, MD, PhD, a physician-scientist in the Healey Center for ALS at Massachusetts General Hospital, is using an innovative type of clinical trial, called a platform trial, to more efficiently test multiple drugs for ALS treatment.

The HEALEY ALS Platform Trial, sponsored by Merit Cudkowicz, MD, MSc director of the Healey Center, is being conducted at over 70 sites of the Northeast ALS Consortium (NEALS) across the U.S.

In a recent commentary in Nature Aging, Paganoni and co-authors, including Brittney Harkey, PhD, Elisa Giacomelli, PhD, and Cudkowicz, highlight key aspects involved in the design and implementation of the ALS platform trials, and their implications for other neurodegenerative and aging-associated diseases in the future.

We asked Paganoni to tell us more about the commentary and the HEALEY ALS Platform Trial.

Can you tell us about your recent publication? What audience are you trying to reach, and what are the key takeaway messages?

Sabrina Paganoni: This paper reports the results of the first-ever platform trial for ALS. The primary goal of this trial is to accelerate the development of effective treatments for people with ALS.

What sets this trial apart from a traditional clinical trial is that, rather than testing a single drug, it evaluates multiple treatments simultaneously using a common protocol and shared infrastructure.

This represents a fundamental shift in how new therapies can be introduced to benefit ALS patients faster. In essence, this paper outlines the successful launch and the scientific and operational efficiencies gained using this novel approach during the first four drug regimens.

We used this new approach to test treatments for ALS, but it could also serve as a model for other rare and neurological diseases.

How did you become interested in ALS?

I became interested in ALS when I was a resident due to my mentorship at Spaulding Rehabilitation Hospital under Lisa Krivickas, MD, a researcher personally affected by the disease.

Tragically, she lost her mother to ALS and later developed it herself, eventually passing away before I completed my residency.

She encouraged me to continue her research, connecting me with Merit Cudkowicz, MD, MSc, at MGH, who was conducting transformative ALS trials and later became the chief of Neurology at MGH.

In 2018, Sean Healey, a successful businessman, was diagnosed with ALS and began care under Cudkowicz. His story is inspiring. He recognized the inefficiencies in clinical trials and aimed to expedite the development of new treatments, wanting to leave a legacy in ALS research.

He made a transformative donation, establishing the Healey Center and the HEALEY ALS platform trial—one of the center's signature projects.

The Healey Center is a comprehensive program focused on finding cures for ALS all the way from fundamental research at the bench to translational research to clinical care—our work spans the entire spectrum of research.

In 2020, we launched the platform trial to accelerate drug discovery in ALS, aiming to decrease the time needed to develop treatments while minimizing the expense and the number of participants in placebo groups.

This trial has been a strong collaborative effort between academia, industry, and the patient and scientific communities. By working together, we hope to advance ALS research and foster innovative treatments.

What does treatment for ALS look like today?

There is no cure to completely stop or reverse progression of ALS.

Currently, there are three FDA-approved drugs: two of which are applicable to all forms of ALS and offer modest benefits. Another drug was recently approved for a specific form of ALS, which is associated with a mutation in the superoxide dismutase 1 (SOD1) gene. While mutations in the SOD1 gene only account for about 2% of all cases of ALS, the availability of this targeted approach is transformative for this patient population.

However, significant challenges continue as we need more effective treatments for the remaining 98% of patients.

Currently, ALS treatment focuses not only on medications but also on supportive care. This is referred to as “multidisciplinary care” which offers a range of supportive services that we provide comprehensively at the MGH ALS clinic.

We work with teams of nurses, physical therapists, occupational therapists, assistive technology specialists, psychologists, and speech therapists. We supply equipment and medications for symptom relief, as well as nutrition and breathing support to help patients function and improve their quality of life.

However, these measures cannot stop or reverse the disease—which is our ultimate goal.

Therefore, in addition to providing comprehensive patient-centered multidisciplinary care, we also want to develop new treatments to stop the disease altogether.

How is your work different from previous studies on ALS? What challenges or barriers does the platform trial model help to address?

Traditionally, clinical trials have operated in a silo. In other words, each company tests its own drug independently. If a drug works, that’s great. If it doesn’t, the project moves on without lessons learned that could benefit future efforts.

To use an analogy, imagine having to construct an entire stadium for every football game you play, only to dismantle it afterward and start over again.

That's not how things function in sports; multiple stadiums are built and then games are played on the same infrastructure season after season.

This is the idea of platform trials, where we establish the necessary foundation in advance, enabling us to conduct multiple tests, or 'games', increasing our chances of success.

Instead of working independently, collaborating with shared infrastructure and processes allows us to achieve two things.

First, we can expedite the testing of each drug with reduced resources and costs. Second, having common processes means we can share data that benefits the entire community, not just testing the drugs but also learning more about the disease itself.

How could the platform model be applied to other diseases?

Since we started the trial, we've been asked to meet with several other groups that do research in different disease areas, in and out of neurology.

We have been sharing what we’ve learned from our experiences and supporting numerous groups, as there is an increasing awareness of platform trials providing a more efficient approach to research.

However, platform trials require a strong commitment, which is why I think there aren’t as many out there. It takes a focused group of individuals who are genuinely passionate about transforming their field.

How do you handle running a trial in over 70 locations?

Our commitment is to provide new options to patients wherever they are. This is a community effort that is fundamentally grounded in robust partnerships with many stakeholders within the entire ALS community, including patients.

Before this trial, companies often selected only a few sites for their individual trials, which limited patients' access based on their location. For example, if you lived in a city with only one trial available, that would be your only option unless you could travel extensively.

With our platform trial approach, we’ve improved access to care. We started with 54 sites, and due to the high demand from both patients and investigators, we've expanded to a network of over 70 sites.

People are eager to engage in transformative research, and we’ve been given the chance to serve individuals across different geographic regions and care settings, from big academic hospitals to smaller private practices and from urban to rural areas.

Although the trial doesn’t cover every city in the U.S., it’s the largest of its kind that has allowed access to multiple drugs at all locations. So, regardless of where you live, you have the same opportunities to access these drugs.

Would you like to talk about any collaborators you’ve worked with?

The commentary was co-authored by myself, along with Cudkowicz, Giacomelli, a neuroscientist, and Harkey, a senior project manager at our institute. We are all fully committed to funding treatments for ALS and are devoting our careers to this pursuit.

We wrote the article on behalf of a large study group, which includes over 200 people.

This trial wouldn’t be possible without the involvement of clinicians and researchers from all the sites in our network, as well as the investigators and scientists contributing to the scientific and statistical designs of the study.

Additionally, the trial participants and their families are making significant commitments of time and effort to participate in this clinical research project, and it is because of this shared partnership that we can make progress.

What does the future look like for your research and for patients with ALS?

If you look at the history of this disease, there’s been an acceleration in investment since the Ice Bucket Challenge a decade ago.

This year marks the 10th anniversary of that challenge, which has spurred a number of initiatives, new grants, and new research investments, with federal funding consistently rising as well. The community's great advocacy has played a crucial role in this progress.

As a result, we are now beginning to witness the outcomes of these efforts. We have seen an acceleration in terms of the sheer number of people working on ALS, along with the number of publications and discoveries in the last five years.

There have been a lot of breakthroughs in terms of the genetics and the cellular and molecular mechanisms that cause ALS.

The number of clinical trials is continuing to grow, and we are hopeful that we’re going to see progress soon.

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Paper Cited

Paganoni, S., Harkey, B., Giacomelli, E., Cudkowicz, M., & HEALEY ALS Platform Trial Study Group (2024). Lessons from the HEALEY adaptive platform trial in amyotrophic lateral sclerosis. Nature aging, 4(11), 1512–1515. https://doi.org/10.1038/s43587-024-00740-x