Amyotrophic lateral sclerosis, better known simply as ALS or Lou Gehrig's disease in honor of the well-known baseball player who died from it decades ago, is a rare disease many may have heard of, but few understand.
Millions of people around the world took the ALS Ice Bucket Challenge when it went viral in 2014, dumping a bucket of ice over their heads to raise awareness and funds for ALS research. However, while most people may be aware of ALS, they might not know much about it, except that it’s a devastating disease with few effective treatment options.
The ALS Association estimates that about 5,000 people in the U.S. are diagnosed with ALS every year, amounting to about 15 new cases every day. ALS is a debilitating and fatal neurodegenerative disease that affects nerve cells in the brain and spinal cord and leads to paralysis and then death within a few years of the first symptoms appearing.
Thus far, doctors have had little success treating this disease. All but one of the available medications merely treat the symptoms of ALS. In fact, the one drug that does treat it directly only extends the patient's lifespan by up to five years. In honor of ALS Awareness Month in May, I'm highlighting four publicly traded biotech companies working on potentially life-changing treatments for ALS.
The current standard of care for ALS
ALS occurs when the motor neurons responsible for movement gradually die. These motor neurons connect the brain with the spinal cord and the spinal cord with the muscles. As these neurons gradually die, it progressively limits and then destroys the patient's ability to move the affected muscles. About 5% to 10% of ALS cases are referred to as “familial,” meaning they run in families, while about 90% occur in patients with no known family history of the disease or genetic mutation linked to it.
There is no cure for ALS, which causes death within a few years of diagnosis, although researchers continue to look into potential treatments. Several new ALS therapies are currently in the preclinical stage and may offer promise for patients.
However, for now, the current standard of care for ALS mostly involves treating the patient's symptoms. The one drug that's been a mainstay in ALS treatment for almost 30 years is riluzole, approved by the FDA in 1995 and now available in generic form.
Riluzole has been clinically shown to extend the lives of ALS patients by three to five months. In fact, a study published in October 2022 found that delaying the beginning of riluzole treatment by one year may reduce the median survival by almost 2 months. A two-year delay was found to reduce the patient's median survival by almost five months.
Riluzole is the only FDA-approved medication to treat ALS systemically. The drug is believed to work by protecting the nerves in the brain and spinal cord from glutamate, a nonessential amino acid that's critical to normal functioning of the brain. It's believed that too much glutamate may be one of the causes of nerve damage.
Targeted outcomes
The gold-standard for ALS treatments until now is slowing the progression of the disease, thereby extending the patient's life. A secondary outcome is to treat the many symptoms of this devastating disease, which has been the route most approved ALS medications have taken over last 12 years.
Including riluzole, there are seven drugs currently approved to treat ALS and its symptoms in the U.S. The other six drugs are Qalsody, RELYVRIO, Radicava, Tiglutik, Exservan and Nuedexta. Two of these treatments, Tiglutik and Exervan, are alternate formulations of riluzole. They are designed to make it easier for ALS patients who have to crush the pill to be able to take it and for those with swallowing problems that make it difficult to take the medication.
In April, the U.S. Food and Drug Administration authorized Biogen's (BIIB) Qalsody, the first drug for a rare genetic form of ALS, although concerns about its effectiveness remain. The fact that it was approved despite a lack of evidence supporting its effectiveness demonstrates how desperate the search for treatments has become.
Another new ALS drug is Amylyx Pharmaceuticals' (AMLX) RELYVRIO, which was approved in September 2022. It combines two drugs, taurursodiol and sodium phenylbutyrate and is designed to slow the disease's progression by blocking stress signals in nerve cells and preventing cell death. Early data suggests the drug may extend the lives of ALS patients by up to 10 months.
However, the search for additional treatments continues, with multiple clinical trials underway.
Athira Pharma
One drug currently in clinical trials is Athira Pharma's (ATHA) ATH-1105. The company announced clinical trials for the drug candidate in February 2023. Athira is developing small-molecule compounds designed to boost the body's naturally occurring repair system to promote cell regeneration, provide neuroprotection, and hopefully modify neurodegenerative diseases. ATH-1105 for ALS treatment is currently in the IND-enabling stage, meaning it's undergoing a series of preclinical pharmacology, toxicology, metabolism, and manufacturing studies with the ultimate goal of filing an investigational new drug (IND) application.
In January, Athira announced preclinical data indicating that ATH-1105 improved motor function and protected against nerve damage in a mouse model of the disease. The mice that received the drug continued to have significantly higher body weight, suggesting they were in better health. They also had significantly lower levels of inflammatory markers and reduced levels of neurofilament light chain, a nerve damage marker.
Based on those results, Athira plans to file an investigational new drug application with the FDA to request permission to start clinical trials in humans.
BrainStorm Cell Therapeutics
BrainStorm Cell Therapeutics (BCLI) is developing NurOwn, a stem cell therapy for ALS. The development process for this treatment has been bumpy, with the FDA rejecting BrainStorm's approval application in November 2022 after the drug candidate failed to meet its primary endpoint in a Phase 3 trial.
However, the agency decided in March to hold an advisory committee (AdCom) meeting to discuss NurOwn, so BrainStorm's ALS treatment isn't dead just yet. The FDA reversed its rejection, at least temporarily, after advocates for ALS patients pushed for the stem cell treatment to be given consideration despite its missed primary endpoint. They cited the high unmet need in ALS, and the FDA apparently agrees that this extenuating circumstance calls for further analysis of NurOwn.
The stem cell treatment involves taking the stem cells derived from the patient's own bone marrow, treating them in a lab, and then putting them back into the patient via an injection along their spine. While the AdCom meeting doesn't guarantee approval for NurOwn, it comes on the heels of a similar situation involving BioGen's Qalsody, which received approval after an AdCom meeting despite missing its primary efficacy endpoint in a Phase 3 study.
Coya Therapeutics (Disclaimer: the author is the founder and CEO of Quantum Media, and Coya is a client of Quantum Media Group, LLC.)
Coya Therapeutics (COYA) is developing a promising and unique treatment for ALS that targets regulatory T cells, also known as Tregs. COYA 302 has gone through a proof-of-concept open-label study in ALS patients and is now in the IND-enabling stage with plans to initiate a larger clinical trial later this year.
The latest results from a proof-of-concept study on COYA 302 were released in March and shared at the Muscular Dystrophy Association's MDA Clinical and Scientific Conference in Texas. COYA 302 is designed to reduce neuroinflammation by increasing the activity of Tregs, a type of anti-inflammatory immune cell, and decreasing the activity of pro-inflammatory immune cells.
In the proof-of-concept study, four ALS patients received COYA 302 for 48 weeks and were then followed for another eight weeks after they stopped receiving the drug candidate. Before beginning the trial, the participants' scores on the Revised ALS Functional Rating Scale (ALSFRS-R) were declining by about one point per month.
During the study, researchers observed no average decline from baseline to 24 weeks and "minimal" average decline from baseline to 48 weeks. Coya Therapeutics plans to begin a larger and well controlled Phase 2 clinical trial for its Treg-based treatment later this year.
uniQure with Apic Bio
In January, uniQure (QURE) and privately held Apic Bio announced that they had entered into a global licensing agreement for APB-102, a clinical-state gene therapy for ALS patients with mutations in the SOD1 gene. Mutations in this gene account for about one-fifth of all familial forms of ALS.
The FDA has already cleared the investigational new drug application for the drug candidate and granted it fast-track and orphan-drug designations. APB-102 is designed as a novel, one-time gene therapy administered via an injection in the space between the thin layers of tissue covering the spinal cord and brain.
The gene therapy is designed to knock down the expression of the SOD1 gene and slow or possibly even reverse the progression of ALS in patients with mutations of that gene. Preclinical studies in an SOD1-ALS mouse model indicated that APB-102 significantly boosted survival. UniQure plans to begin a Phase 1/ 2 trial of APB-102 later this year.
Investing in clinical-stage ALS treatments
Unfortunately, many biotech firms have faced setbacks when their proposed ALS treatments failed their endpoints in clinical trials, illustrating the difficulties in developing effective treatments. However, the high unmet need continues to drive the FDA to consider approving treatments that may not have demonstrated clear effectiveness, showing significant opportunity in the space.
One estimate pegs the global ALS treatment market at $719.2 million in 2022 and projects a 4.9% compound annual growth rate through 2028, reaching $969.3 million. The growing geriatric population and increasing incidence rate are driving growth in the market. Many other clinical-stage treatments for ALS are also under development by privately held companies like Verge Genomics and QurAlis.
The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.
Ari Zoldan
Ari Zoldan is the CEO of New York-based Quantum Media Group, LLC. The company provides investor relations, public relations and equity research services to publicly traded companies. As an on-air media personality, Ari can be seen regularly on major media outlets and is frequently quoted in mainstream news outlets covering business, innovation and emerging trends.
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