Industry partners from the companies noted below are working closely with the Healey Center Trial Design Team, the Northeast ALS Consortium (NEALS), Barrow Neurological Institute and Berry Consultants to tailor the arm of the HEALEY ALS Platform Trial to their experimental study drugs. Visit the trial page on ClinicalTrials.gov for more information about sites, treatments, and trial participation criteria.
Zilucoplan, by UCB - Now Enrolling
Zilucoplan, an oral myeloperoxidase inhibitor, is a small macrocyclic peptide inhibitor of complement component 5 [C5]. The complement system, as part of the innate immune system, is a group of proteins that evolved to protect humans from bacterial infections. In many diseases, inappropriate complement activation and deposition can occur damaging tissues and organs. Robust experimental data supports a role for complement activation and deposition in both the peripheral and central nervous systems in amyotrophic lateral sclerosis (ALS).
Zilucoplan, a new drug candidate developed by UCB (formerly Ra Pharmaceuticals), binds complement component 5 (C5) and inhibits tissue damage caused by pathological complement activation. Clinical data in a Phase 2 trial of zilucoplan in another neuromuscular condition generalized myasthenia gravis, demonstrated rapid, clinically meaningful and statistically significant improvements, as well as a favorable safety and tolerability profile. Zilucoplan has been designed for convenient “in-home” use by patients and is self-administered as a small volume, subcutaneous administration.
Verdiperstat, by Biohaven Pharmaceutical Holding Company Ltd. – Now Enrolling
Bioenergetic Nanocatalysis (CNM-Au8, nanocrystalline gold) by Clene Nanomedicine, Inc. – Now Enrolling
Motor neurons consume significant energy in order to function normally. In ALS, corrupted energy metabolism together with increased cellular stress lead to motor neuron degeneration. CNM-Au8 is a new class of medicine that provides an energetic assist to impaired motor neurons, helping them improve their ability to function more normally. CNM-Au8 acts catalytically to both support bioenergetic reactions inside cells and eliminate the harmful waste byproducts of cellular metabolism. Oral delivery of CNM-Au8 resulted in both neuroprotection and remyelination in multiple animal studies. Each 2 oz dose of CNM-Au8 is a concentrated, liquid suspension of pure gold nanocrystals that study participants drink every morning. These extremely small nanocrystals travel through the body and enter the brain and motor neuron cells where they enhance the ability of these cells to survive and communicate by supporting cellular metabolism. CNM-Au8 was demonstrated to be safe and well-tolerated by healthy volunteers in a Phase 1 study.
Pridopidine, by Prilenia Therapeutics – Now Enrolling
Pridopidine is a highly selective Sigma-1 receptor (S1R) agonist developed by Prilenia for the treatment of neurodegenerative and neurodevelopmental disorders. S1R regulates key cellular pathways, commonly impaired in neurodegeneration. Of particular interest is its role in the pathogenesis of ALS which is supported by human genetic and postmortem studies as well as by preclinical models. Pridopidine demonstrates robust neuroprotective effects in numerous preclinical models of neurodegenerative diseases including models of ALS. Compelling preclinical data supports the therapeutic potential of pridopidine in ALS. In ALS SOD1G93A motor neurons (MNs), pridopidine exerts neuroprotective effects via activation of the S1R. Specifically, pridopidine increases MN survival, improves BDNF and GDNF axonal transport, and restores the neuro-muscular junction (NMJ) synaptic activity. In vivo, pridopidine treatment of SOD1G93A mice reduces toxic protein aggregates and ameliorates muscle fiber wasting.
Clinical support for the validity of the S1R as a potential target for ALS can be derived from a prior trial using a non-selective S1R agonist, showing S1R activation may enhance bulbar and speech function in ALS patients. Pridopidine in vivo target engagement in humans is validated by PET imaging, providing support of the optimal clinical dose. Prior clinical data with pridopidine demonstrates a favorable safety and tolerability profile and provides evidence for a beneficial effect on functional outcome in another neurodegenerative disease.
Trehalose (SLS-005), by Seelos Therapeutics – Preparing for Testing
Trehalose is a low molecular weight disaccharide (0.342 kDa) that crosses the blood-brain barrier, stabilizes proteins and, importantly, activates autophagy, which is the process that clears pathologic material from cells. In animal models of ALS treatment with trehalose delayed onset of disease, prolonged survival and preserved motor function and motor neurons in the spinal cord. Trehalose activates autophagy through the activation of Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression. Activation of TFEB is an emerging therapeutic target for a myriad of diseases with pathologic accumulation of storage material. The drug is manufactured by Seelos Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on the development of therapies for central nervous system disorders and rare diseases.