What are the current clinical trials or treatments for Amyotrophic Lateral Sclerosis (ALS)?

From the Guidelines

The current standard of care for Amyotrophic Lateral Sclerosis (ALS) should prioritize access to multidisciplinary care, including respiratory assist devices (RAD) and in-home respiratory care, as emphasized in the 2024 report by the National Academies of Sciences, Engineering, and Medicine 1. The most recent evidence suggests that the use of RAD offers greater quantity and quality of life for individuals with ALS, and Medicare qualification for RAD reimbursement should be updated to align with current best practices, which require a forced vital capacity (FVC) below 50% 1. Some of the current clinical trials and treatments for ALS include:

• Relyvrio (sodium phenylbutyrate and taurursodiol), which was FDA-approved in 2022
• NurOwn: A stem cell therapy using the patient's own cells
• Masitinib: A tyrosine kinase inhibitor being studied for its neuroprotective effects
• Verdiperstat: An oral myeloperoxidase inhibitor targeting neuroinflammation These treatments aim to slow disease progression by addressing different aspects of ALS pathology, such as oxidative stress, neuroinflammation, and motor neuron degeneration. Key aspects of ALS care and research that need to be addressed include:
• Creating a sustainable and accessible ALS clinical care and research system
• Providing access to multidisciplinary care for all individuals with ALS
• Ensuring equitable access to multidisciplinary care and research systems
• Supporting unpaid caregivers and providing access to VA care and resources
• Enhancing equity and reimbursement for centralized resources and ALS clinical trials network 1. Ultimately, a multidisciplinary approach remains crucial for comprehensive ALS care, and patients should consult with their neurologist to determine eligibility and potential benefits of participating in clinical trials 1.

From the FDA Drug Label

The efficacy of riluzole tablets was demonstrated in two studies (Study 1 and 2) that evaluated riluzole tablets 50 mg twice daily in patients with amyotrophic lateral sclerosis (ALS). Both studies included patients with either familial or sporadic ALS, a disease duration of less than 5 years, and a baseline forced vital capacity greater than or equal to 60% of normal

The current clinical trials or treatments for Amyotrophic Lateral Sclerosis (ALS) mentioned in the drug label include:

• Riluzole 50 mg twice daily: shown to be effective in two studies (Study 1 and 2) in patients with ALS, with a longer time to tracheostomy or death compared to placebo 2 There is no information on other current clinical trials or treatments for ALS.

From the Research

Current Clinical Trials and Treatments for ALS

• There are currently three FDA-approved disease-modifying treatments for ALS: edaravone, riluzole, and sodium phenylbutyrate and taurursodiol (PB/TURSO) 3.
• A fourth therapy has been recently approved under accelerated approval and is contingent upon verification of clinical benefit in confirmatory trials 3.
• Therapy selection is based largely upon patient characteristics, as guidelines have not been updated since the recent approval of PB/TURSO or accelerated approval of tofersen 3.
• Managing ALS symptomatically is important to improve patients' quality of life, and providers use symptomatic treatments to address common symptoms such as anxiety, depression, and muscle cramps 3.

Emerging Agents and Experimental Treatments

• Emerging agents offer some hope for patients with ALS, including an oral tyrosine kinase inhibitor, RIPK1 inhibition, the use of mesenchymal stem cells, antisense oligonucleotides, and modification of the patient's own mesenchymal stem cells 3.
• Riluzole is the only disease-modifying drug approved for the treatment of ALS, and it has been demonstrated to extend survival 4, 5, 6.
• The overall tolerability of riluzole is good, but it can cause adverse events such as asthenia, nausea, and elevations of transaminases 4, 6.
• Riluzole prolongs survival in the last clinical stage of ALS, and this finding needs to be confirmed in a prospective study 7.

Riluzole Clinical Trials

• Two double-blinded, placebo-controlled clinical trials of riluzole have been carried out in more than 1,100 patients with ALS, showing a modest benefit in prolonging survival 5, 6.
• A dose-ranging study of riluzole in ALS patients confirmed that the 100 mg dose has the best benefit-to-risk ratio 6.
• Riluzole has been available for use in the United States since 1996, and it begins a new era in both basic and clinical research in an attempt to find a cure for ALS 5.