Exploring FDA-Approved Drugs and Potential Treatment Options for ALS

ALS 

Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, is a fatal, progressive, neurodegenerative disease that affects nerve cells in the brain and spinal cord. This disease leads to the gradual degeneration and death of motor neurons — nerve cells that control voluntary muscles. As the motor neurons die, the muscles they control weaken and waste away, leading to progressive loss of muscle movement, including the ability to speak, swallow, and breathe. The condition ultimately leads to paralysis and death.  

Although there is no cure for ALS, numerous treatments are now available to help manage symptoms and improve the quality of life for those with the condition. The ALS Ice Bucket Challenge, which raised $115 million in donations in 2014, significantly amplified the ALS Association's ability to invest in promising research, advance assistive technologies, and enhance access to care for individuals affected by ALS. 

FDA-Approved Treatments 

As of 2023, seven drugs have been approved by the FDA to treat ALS and its symptoms: Qalsody, Relyviro, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. Additional potential treatments are in the clinical trial pipeline to test safety and efficacy before seeking FDA approval. 

Qalsody (Tofersen) 

Biogen’s Qalsody, also known as tofersen or BIIB067, was approved by the FDA in April 2023 to treat a rare form of ALS associated with a mutation in the superoxide dismutase 1 (SOD1) gene — roughly 2% of the ALS population. 

The drug can slow down muscle degeneration in those eligible for treatment by targeting SOD1 messenger RNA (mRNA), which instructs the body on protein production and reduces the production ofSOD1 proteins. 

According to the FDA, clinical studies showed that the drug reduced plasma neurofilament light (NfL), a blood-based biomarker of axonal (nerve) injury and neurodegeneration. 

Relyvrio (AMX0035) 

Relyvrio (AMX0035), manufactured by Amylyx Pharmaceuticals, is a drug combination of sodium phenylbutyrate and taurursodiol, which can prevent nerve cell death by blocking stress signals. The FDA approved Relyviro for treating ALS in 2022. 

Radicava (Edaravone)  

Mitsubishi Tanabe Pharma America’s Radicava (edaravone) was the first new treatment specifically for ALS approved by the FDA in 2017 after a gap of 22 years. An oral formulation was also approved in 2022. 

Riluzole 

Recent peer-reviewed research suggests that riluzole is a promising treatment option for ALS.  

By decreasing glutamate levels, riluzole is believed to slow the progression of ALS and extend survival by a few months. Riluzole is typically used with other treatments and therapies, such as physical therapy and respiratory care, to help manage the symptoms of ALS. 

Rilutek (Riluzole)  

Covis Pharma’s Rilutek (riluzole) was the first FDA-approved drug to treat ALS in 1995. It inhibits glutamate release and can prolong life by approximately three months. Riluzole is the generic name of Rilutek and has been available since 2003. 

Tiglutik (Thickened Riluzole) 

Tiglutik (thickened riluzole), manufactured by ITF Pharma, is the first and only thickened liquid form of riluzole, approved by the FDA in 2018. Unlike the oral pill form, it avoids the potential problems associated with crushing tablets. 

Exservan (Riluzole Oral Film) 

Exservan (riluzole oral film), also created by Mitsubishi Tanabe Pharma America, is an oral film formulation of riluzole approved by the FDA in 2019. It is developed for patients with severe swallowing difficulties and dissolves on the tongue, bypassing the need to swallow a pill or liquid. 

Nuedexta 

Otsuka America Pharmacutical’s Nuedexta, FDA-approved in 2011, is indicated for treating pseudobulbar affect (PBA), a condition characterized by frequent, exaggerated episodes of crying or laughing that don't match how the person feels. It occurs secondary to various neurologic disorders, including ALS. Nuedexta (dextromethorphan HBr and quinidine sulfate) can effectively treat PBA. 

Promising Clinical Trial Treatments 

Currently undergoing clinical trials, RAPA-501 autologous T cells, arimoclomol, insulin-like growth factor-1 (IGF-1), and stem cell therapy (NurOwn) are treatments being investigated for ALS. These therapies aim to address the underlying mechanisms of the disease and  

RAPA-501 Autologous T Cells 

RAPA-501 is a potential therapy for ALS currently in phase 2/3 clinical trials. RAPA-501 is an oral medication that targets inflammation and oxidative stress, both of which have been implicated in the progression of ALS. 

Inflammation and oxidative stress cause damage to neurons, leading to their death and the subsequent loss of muscle control that characterizes ALS. RAPA-501 works by inhibiting an enzyme called p38 MAP kinase, which plays a vital role in the inflammatory response and the production of reactive oxygen species. 

By reducing inflammation and oxidative stress, RAPA-501 may slow the progression of ALS and improve patients' quality of life. However, it's important to note that RAPA-501 is still in clinical trials, and its effectiveness and safety must be fully established. It's always best to consult a medical professional on the most appropriate treatment options for ALS. 

Arimocomol 

Arimoclomol is another potential treatment for ALS. It is an experimental drug currently in clinical trials that increases the production of heat shock proteins, which help protect cells from damage and promote their survival. By increasing the production of heat shock proteins, arimoclomol may be able to protect motor neurons from damage and slow the progression of ALS. 

Clinical trials of arimoclomol have shown promising results in slowing functional decline in people with ALS. However, the drug is still undergoing further testing, and its safety and effectiveness must be fully established. It's essential to consult a medical professional for advice on the most appropriate treatment options for ALS. 

Insulin-Like Growth Factor-1 (IGF-1) 

Insulin-like growth factor-1 (IGF-1) is a naturally occurring protein in the body that promotes cell growth and survival, including the growth and maintenance of nerve cells. Studies have suggested that IGF-1 may be involved in the development and progression of ALS and that increasing levels of IGF-1 may have a protective effect on the motor neurons damaged in ALS. 

As a result, researchers have been exploring the potential use of IGF-1 as a treatment for ALS. Several clinical trials have investigated the safety and efficacy of IGF-1 therapy in people with ALS. These trials have used different methods of delivering IGF-1, including injections and intrathecal infusion (into the spinal fluid). 

While some studies have shown promising results in slowing the disease's progression and improving muscle strength and function, others have not shown significant benefits of IGF-1 therapy in people with ALS. As a result, IGF-1 as a treatment for ALS is still considered experimental and further research is needed to determine its safety and effectiveness. 

NurOwn (Stem Cell Therapy)  

Recent studies have suggested that mesenchymal stem cells (MSCs) may have the potential to treat ALS. MSCs — stem cells that can differentiate into various cell types, including musculoskeletal system cells — can modulate the immune system and reduce inflammation, which may be beneficial in managing neurodegenerative conditions. 

Several reviewed studies have found that MSCs were generally well-tolerated and had a favorable safety profile, with no serious adverse effects reported. However, results of clinical trials were mixed, with some reporting improvements in muscle strength and function and others finding no significant benefits. 

For example, BrainStorm’s NurOwn is a novel investigational cell therapy being studied as a potential treatment for ALS. The therapy involves harvesting stem cells from a patient's own bone marrow, which are then treated with specific growth factors that cause them to differentiate into cells that produce a range of neurotrophic factors (NTFs). NTFs are proteins that support the survival and growth of nerve cells. It is thought that increasing their production in the body may slow or halt the progression of ALS. 

The treated cells, called NurOwn cells, are infused back into the patient's body via a spinal injection. The hope is that these cells will migrate to the site of damage in the motor neurons and release the NTFs, which will help protect the neurons from further damage and support their survival. 

After reviewing the pivotal phase 3 trial (NCT03280056) of NurOwn in March 2021, which involves the use of autologous mesenchymal stromal cells secreting neurotrophic factors [MSC-NTF] cells, the FDA determined that the available data did not meet the required threshold of substantial evidence to support a Biologics License Application (BLA).  

The original study results revealed that NurOwn did not achieve statistical significance in its primary endpoint, with only 33% and 28% of those on MSC-NTF and placebo, respectively, demonstrating a change in disease progression of at least 1.25 points on the ALS Functional Rating Scale (ALSFRS-R) after 28 weeks of treatment. 

Over a year later, in August 2022, BrainStorm disclosed new clinical analyses that reinforced NurOwn's results. While the initial results have been promising, more research is needed to fully understand its potential as an ALS treatment. 

As the use of MSCs and other treatment options continues to be a topic of ongoing research and debate, further studies are needed to fully understand their potential benefits and risks. Individuals with ALS must work closely with their medical team to determine the most appropriate treatment plan.