Amyotrophic lateral sclerosis (ALS) is a lethal, relentlessly progressive neurodegenerative disease, and the most common adult-onset motor neuron disorder. Though it can strike at any time, ALS is often diagnosed in middle age when the person is in the “prime of life.” There is no good time for a family to face ALS, but the age of onset adds additional financial and emotional complexities. Patients diagnosed with ALS experience continual worsening, often ending in respiratory failure, three to five years after diagnosis.
Despite decades of focused research, only a few therapeutic options are available for ALS patients. What’s more, the medications that are FDA-approved to date provide only symptomatic management with relatively modest impact. No known treatments exist to stop or reverse the course of disease progression.
For patients and their families, an ALS diagnosis is devastating. PRA’s Jane Fletcher, Central Monitoring Associate for North America, sees the impact the disease has on patients’ daily lives through her work running ALS studies at PRA. She recalls her time caring for a patient diagnosed with ALS while working as a nurse in an internal medicine clinic. “I had to watch her decline over the months, and it tugged at my heart. I’m hopeful that a treatment breakthrough is on the horizon.”
In addition to a lack of care options, ALS research poses many challenges for drug developers and patients alike. Despite these obstacles, PRA remains focused on providing reliable care options and developing life-changing treatments for ALS patients and their unique circumstances.
Fortunately, a new clinical trial may be a powerful weapon in the battle against ALS. The HEALEY ALS Platform Trial is a perpetual, multi-center, multi-regimen clinical trial designed to evaluate ALS treatment options. Unlike non-platform trials, the HEALEY trial allows for multiple investigational products to be tested simultaneously or sequentially, which will hopefully lead to faster approval of safe and more effective treatment options for ALS patients.
This platform trial comes not a moment too soon for ALS patients and their loved ones. Those that have had the chance to meet the ALS patient community—the patients themselves, their families, and the tireless clinic teams who provide their care while trying to bring a real solution—feel their urgent need for a treatment we just don’t have yet. Fortunately, the clinical research community is getting closer every day. By working together, we can bring the change ALS patients so desperately need.
Challenges in ALS Clinical Research
In recent years, the need for new ALS therapeutics made global headlines. The widely publicized 2014 ALS Ice Bucket Challenge increased annual funding for ALS research by 187 percent, drawing unprecedented attention to the disease and the race to develop treatments.
ALS patients are highly motivated, too. “We know there are ALS patients everywhere looking for a new treatment to change their devastating disease,” says Global Project Director Beate Brouwer, who oversees PRA’s global ALS study across all regions.
Despite overwhelming public support, factors specific to the disease itself continue to cause significant challenges when it comes to clinical trial recruitment and research.
The disease course is rapid.
A patient must undergo a rigorous investigation period, which can take up to a year, with the elimination of other possible diseases in order to receive an official diagnosis of ALS. This evaluation includes medical history, physical examinations, electrodiagnostics, neuroimaging, and laboratory assessments. A patient’s ALS continues to progress during this time, and it can fatally impair respiratory function within just a few years. In addition, the likelihood of slowing the illness or reversing its course is greatly reduced as neurologic damage increases. As such, clinical trials generally will not enroll participants with advanced disease because products in development have not yet been able to target reversal of the disease. The long diagnostic window for ALS, combined with its limited survivability, makes recruitment and enrollment in clinical trials exceedingly difficult.
The causative mechanism is unknown.
One of the most psychologically devastating aspects of ALS is that its pathophysiology remains unknown. Up to ninety percent of cases are “sporadic,” occurring without any foreshadowing or identifiable risk factors, making it difficult to develop therapeutics that target a causative mechanism. The remainder of cases are genetically driven. However, even the genetic basis of ALS is widely heterogeneous and complex.
An ALS diagnosis can be all-consuming and devastating for patients and their families.
Patient advocacy can dramatically advance clinical research through increased disease awareness and funding. However, ALS’s rapid disruption and progression make participating in advocacy especially challenging for patients and their families. ALS places emotional, mental, and financial burdens on patients and their loved ones. Receiving an initial diagnosis is a slow and tedious process. However, the disease itself moves quickly, often striking patients who are in their prime earning years and stealing their ability to work and care for themselves and their families, let alone advocate for research advancements.
Research Sites Are Saturated
As of publishing, there are nearly 130 open, planned, or temporarily closed clinical research studies around the world that are currently evaluating patients with ALS. In total, these studies are looking to enroll nearly 10,000 patients—a large percentage of the estimated 220,881 global cases of ALS, and perhaps an even larger percentage of ALS patients who would qualify to take part in many of these studies. Although it is encouraging that so much attention is being devoted to ALS research, the downstream effect of having many simultaneous trials is that the pool of available study participants at each clinical research site is smaller. This makes it harder for each individual study to recruit patients and proceed with enrollment if they rely only on those patients who happen to live near enough to the site that travel would not present a major barrier.
Benefits of an ALS Platform Clinical Trial
Platform trials are clinical trials with a single master protocol implemented in such a way that multiple treatments can be investigated at the same time. These simultaneous interventions are meaningfully coordinated, compared to the uncoordinated efforts of simultaneous non-platform clinical trials that effectively isolate many available ALS patients into placebo arms.
A platform trial gives more patients (75 percent in the HEALEY trial) the opportunity to be randomized into an interventional arm instead of a placebo arm. Platform clinical trials are designed to be continuous, allowing for the exit of treatments that do not prove beneficial and the entry of new treatments as the trials proceed. In this way, a platform trial makes drug development more efficient—and, therefore, brings meaningful treatments to the patients who need them sooner.
Characteristics of the HEALEY ALS Platform Trial
The HEALEY trial is being conducted at more than 50 sites across the United States. The trial will assess the safety profile and effectiveness of multiple ALS therapeutic regimens, starting with three regimens initially. Characteristics of the trial include:
- A universal study method will be applied to each regimen, and the initial regimens will be evaluated simultaneously.
- Each regimen will be assessed with a placebo-controlled trial, and participants will be randomized into investigative or placebo groups.
- New therapeutic regimens will be continuously added as the trial proceeds, prompting the enrollment of additional participants.
The study’s particular platform design, the first of its kind for ALS, addresses many of the research challenges faced by the ALS community. The trial is a terrific win-win. Expert clinical research sites can efficiently collect high-quality clinical trial data, which reduces overall development timelines for all investigational products being tested now and in the future.
The HEALEY trial’s design will enable the FDA to review the value of each intervention more quickly than would otherwise be possible if a full independent arm of placebo-controlled participants were needed, and has the potential to bring meaningful treatments to patients sooner than could be achieved otherwise.
Crossroads of ALS Advocacy and Policy
We’re currently at a complicated intersection of advocacy and policy surrounding ALS research. All of the approved ALS drugs provide incremental developments aimed at extending lifetime—not curing the disease. While these incremental improvements can certainly make a worthwhile impact on the lives of ALS patients and their families, they do not change the fact that a durable solution is still needed.
The exciting development of a platform trial within the ALS research space offers both hope and opportunity for patients and drug developers alike. Today, only a limited number of clinical research sites expertly work with ALS patients. We must think of ALS clinical sites and research consortia the same way we think of patients—as our partners. Forging strategic, lasting relationships with them can further clinical innovation.
Research consortia’s singular aim is to bring treatments to market without any vested interest in which individual therapeutics ultimately prevail. The HEALEY ALS platform trial illustrates how these sites can serve as unbiased, neutral hosts that can help us bring meaningful treatments to ALS patients who need them now.
RARE DISEASES NEWSLETTER Volume 13, May 2019
Welcome to the thirteenth edition of the rare diseases newsletter. This quarterly publication strives to keep you up to date on PRA's Center for Rare…
Center for Rare Diseases continues to engage with rare disease patient communities during COVID-19 crisis
PRA Health Sciences’ Center for Rare Diseases is committed to engaging rare disease patient communities, and providing transparency, throughout the…
Healthcare Intelligence: Q&A with Laura Iliescu
Laura Iliescu, Manager of Patient Advocacy & Engagement, Center for Rare Diseases, is an adventurer and explorer. She dives into challenges the…