Study Drugs in the HEALEY ALS Platform Trial
For Industry/Pharma with ALS Pipeline
The HEALEY ALS Platform Trial will keep adding treatment arms. To learn more, pharma companies with a therapy for ALS can contact us via email.
Industry partners from the companies noted below worked closely with the Healey Center Trial Design Team, the Northeast ALS Consortium (NEALS), Barrow Neurological Institute and Berry Consultants to tailor the arms of the HEALEY ALS Platform Trial to their experimental study drugs. Visit the trial page on ClinicalTrials.gov for more information about sites and trial participation criteria.
Regimen F: ABBV-CLS-7262, by Calico and AbbVie- Now Recruiting
ABBV-CLS-7262 is an investigational drug developed by Calico Life Sciences LLC in collaboration with AbbVie Inc. ABBV-CLS-7262 aims to restore function in cells affected by ALS by normalizing protein synthesis and preventing further sequestration and aggregation of TDP-43, thereby protecting neurons, and possibly slowing ALS progression.
The integrated stress response (ISR) is a fundamental transient process that regulates cell function during various stressful conditions. Tissue studies suggest that the ISR is chronically induced in people with ALS. It is proposed that TDP-43 aggregates, a hallmark feature in the motor neurons of people with ALS, could be formed by a chronically induced ISR. ABBV-CLS-7262 activates the protein complex eIF2B, which is a key regulator of the ISR. Binding of ABBV-CLS-7262 desensitizes eIF2B to stress and decreases the ISR. Reduction of the ISR restores normal protein synthesis, reduces TDP-43 sequestration in stress granules, and may decrease TDP-43 aggregation.
A prior first-in-human study of ABBV-CLS-7262 showed that this drug was well-tolerated by participants, demonstrated target engagement by increasing eIF2B enzymatic activity, and suppressed the ISR in blood cells. ABBV-CLS-7262 crossed the blood brain barrier at concentrations predicted to be efficacious in ALS. ABBV-CLS-7262 is currently being investigated in a Phase 1b study in people with ALS (NCT04948645), and will be studied further as part of the HEALEY ALS Platform Trial.
Watch a webinar about the science behind ABBV-CLS-7262
Watch this video for more information on the mechanism of action behind ABBV-CLS-7262.Download General Platform Trial Brochure
Download Regimen F Brochure
Download Lumbar Puncture Brochure
Regimen G: DNL343, by Denali Therapeutics- Not Yet Enrolling
DNL343 is being developed by Denali Therapeutics. DNL343 targets eIF2B, a key regulator of the integrated stress response (ISR). In neurons exposed to cellular stressors, inhibition of the ISR by DNL343 restores protein synthesis and dissolves pre-formed TDP-43 containing stress granules. This effect of DNL343 is of clinical interest because TDP-43 containing stress granules are thought to lead to TDP-43 inclusions, a hallmark of ALS pathology.
No Longer Enrolling
Regimen A: Zilucoplan, by UCB - Enrollment Complete
Zilucoplan 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.
Watch a webinar about the science behind zilucoplan.
Note: On March 1, 2022, the zilucoplan regimen was halted.
Regimen B: Verdiperstat, by Biohaven Pharmaceutical Holding Company Ltd. – Enrollment Complete
Note: On Sept 29, 2022, the topline results for verdiperstat were announced
Regimen C: Bioenergetic Nanocatalysis (CNM-Au8, nanocrystalline gold) by Clene Nanomedicine, Inc. – Enrollment Complete
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.
Watch a webinar about the science behind CNM-Au8.
Note: On Oct 3, 2022, the topline results for CNM-Au8 were announced
Regimen D: Pridopidine, by Prilenia Therapeutics – Enrollment Complete
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.
Watch a webinar about the science behind pridopidine.
Previous research supports pridopidine’s neuroprotective properties in Huntington’s disease models. For more information, you can view information on pridopidine in Huntington's disease or read a selection of published articles about pridopidine.
Note: On Feb 23, 2023, the topline results for pridopidine were announced
Download a brochure about Regimens A-D
Regimen E: Trehalose (SLS-005), by Seelos Therapeutics – Enrollment Complete
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.
Webinar: The Science Behind Trehalose.
Webinar: Healey ALS Platform Trial Regimen E: A Participant’s Guide
Webinar: Update on Healey ALS Platform Trial Regimen E: Trehalose for ALS
Reference Papers on Innovative Trial Design
Platform trials are trials where multiple drugs are tested at the same time, using specialized statistical tools.
Clinical Trial Options at Mass General
At the Sean M. Healey and AMG Center for ALS, we are committed to radical change and acceleration of converting ALS research into enduring treatments.
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