Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative condition that causes a gradual loss of motor neurons in the brain and results in patients slowly losing their motor control. Despite the challenging nature of drug development for neurological diseases and rare diseases, the landscape of ALS research has expanded significantly over the last decade. To date, Rilutek (1995), Radicava (2017), Tiglutik (2018), Exservan (2019), Nuedexta (2011), and Relivrio (2022) are ALS therapies that have all been approved by the United States Food and Drug Administration (FDA) for treating ALS. Read on to discover five emerging ALS therapies that are currently helping drive innovation in the field of ALS research.
1. NurOwn | BrainStorm Cell Therapeutics
NurOwn is the first ALS cell therapy tested by a randomized placebo-controlled study and is derived from each patient’s own mesenchymal stem cells (MSCs). These adult bone marrow MSCs are reported to differentiate into astrocyte-like cells, which secrete important neurotrophic factors (NTFs) and promote the growth of new motor neurons. A pivotal double-blind phase III trial (NCT03280056) tested NurOwn in 196 patients to evaluate the percentage of trial participants who experienced a monthly post-treatment improvement of 1.25 points. Although the trial was unable to meet this primary endpoint with statistical significance (P = 0.45), it did demonstrate noticeable improvements in cerebrospinal fluid (CSF) biomarkers for neuroinflammation and neurodegeneration. Another similar phase III MSC cell therapy program (NCT04745299) is also underway to investigate the safety and efficacy of lenzumestrocel, which has been an approved ALS therapy in South Korea since 2014.
2. Tofersen | Ionis Pharmaceuticals/Biogen
Tofersen is currently in development to combat the toxic activity of SOD1 by reducing its protein production in patients with SOD1-associated ALS. SOD1 is an enzyme that plays a role in apoptosis and is implicated in motor neuron degeneration when mutated. In a completed phase I/II trial (NCT02623699), tofersen use was associated with a 33% reduction in levels of SOD1 protein present in the cerebrospinal fluid by day 85 when compared with the placebo cohort. Based on these promising results, Biogen submitted a New Drug Application (NDA) under the accelerated pathway to the FDA for tofersen. This application was accepted and granted priority review in July 2022, then extended for 3 months in October 2022. A new phase III study (NCT04856982) has also begun to determine the efficacy of tofersen in delaying clinical onset of ALS in pre-symptomatic patients.
3. Aldesleukin | Clinigen
Aldesleukin is a recombinant human interleukin-2 (IL-2) which has been demonstrated to exhibit immunoregulatory properties which may alleviate the neuroinflammation present in ALS. This therapy, named Proleukin, is already approved by the FDA for treating metastatic melanoma and renal cell carcinoma. The phase II IMODALS trial (NCT02059759) tested a low dose of aldesleukin in 36 ALS patients. The results primarily demonstrated a significant, dose-dependent increase in the number of suppressor T (Treg) cells, which suggests better immune system modulation to reduce neuronal loss in ALS. The data from IMODALS led to further evaluation of the most favorable dose of aldesleukin in the phase II/III MIROCALS trial (NCT03039673).
4. Verdepistat | Biohaven Pharmaceuticals
Verdiperstat is a small molecule myeloperoxidase (MPO) inhibitor to dampen oxidative stress pathways and reduces the neuroinflammation associated with ALS and other neurodegenerative diseases. This oral medication was tested for safety and efficacy against a placebo in the phase II/III HEALEY ALS Platform Trial (NCT04297683, NCT04436510). Although this trial did not meet its primary endpoint with statistical significance, verdiperstat highlights an important pathophysiological pathway that likely plays a complex role in promoting neuronal injury. Future therapies may be more successful by targeting multiple pathways at once, due to underlying intricacies of ALS disease activity.
5. AMX0035 | Amylyx Pharmaceuticals
AMX0035, or Relyvrio, is perhaps the most exciting emergent therapy due to its recent approval for market authorization in the U.S. (September 2022) and Canada (June 2022) for treating ALS. This is a disease-modifying oral therapy that is the first to target multiple disease mechanisms at once, including inhibiting the enzyme histone deacetylase and inhibiting mitochondria-related apoptosis pathways. The phase II CENTAUR trial (NCT03127514) evaluated AMX0035 in 137 ALS patients for 6 months. The results demonstrated significantly slower rates of functional decline with the use of AMX0035 compared to the placebo. Other trials testing this therapy include the phase III PHOENIX trial (NCT05021536), as well as future post-marketing trials to further determine the long-term safety of AMX0035 use in treating ALS.
Vial Neurology CRO
As sponsors and contract research organizations (CROs) grasp drug discovery technology and interest in rare disease clinical trials evolves, ALS patients can expect even more treatment options to become available in the future. Vial is a full-service CRO that recognizes the central role of technology in the future of drug development and is paving the way for modernized clinical research through digital innovation. Trusted by leading sponsors, our specialized teams deliver shorter study timelines, quality affordable services, and a clinical trial experience that puts you first. Contact a team member today to discover how we can help you with your ALS research.