Mass General Announces New Trial Design to Speed up Search to Find Approaches for ALS Patients

Sep 18, 2019 | Amyotrophic Lateral Sclerosis (ALS), Platform Trial

Mass General Announces New Trial Design to Speed up Search to Find Approaches for ALS Patients

The Sean M. Healey & AMG Center for ALS at Mass General aims to speed up the search for new approaches to help patients with amyotrophic lateral sclerosis (ALS) through a groundbreaking new trial design, which supports rapid testing of multiple drugs.

Prilenia is a newly formed biotech company focused on developing novel treatments for neurodegenerative and neurodevelopmental disorders. They’ve announced that Pridopidine, its lead compound, has been selected at the first of three potential new treatments to be included in the launch of the first ever platform trial in amyotrophic lateral sclerosis (ALS). Two additional compounds were chosen to join the trial at a later stage.

Why was Pridopidine Chosen?

It was chosen by an independent review committee out of 30 competing investigational treatments based on human genetic data, efficacy in preclinical models, favorable safety profile and readiness of drug supply. A highly selective S1R agonist, its mechanism has already evidenced some benefit to ALS patients.

What is Pridopidine?

Formerly called ACR16 (ASP2314), it is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. These compounds may counteract the effects of excessive or insufficient dopaminergic transmission, and are therefore under investigation for application in neurological and psychiatric disorders characterized by altered dopaminergic transmission, such as Huntington’s disease.

Compelling preclinical data supports a therapeutic potential for pridopidine in ALS, In ALS SOD1G93A motor neurons (MNs), pridopidine exerts neuroprotective effects via activation of the S1R. Specifically, pridopidine improves BDNF and GDNF axonal transport, restores synaptic activity and the neuro-muscular junction (NMJ) function and increases neuronal survival. 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 learned from previous data suggesting S1R activation may enhance bulbar and speech function in ALS patients.

Who is Leading the Platform Trial

This innovative platform trial is led by the Sean M. Healey & AMG Center for ALS at Mass General Hospital. The trial design aims to accelerate the development of effective treatments for people living with ALS, by testing and evaluating multiple treatments simultaneously.

The HEALEY ALS Platform Trial will be the second clinical trial initiated by Prilenia. Earlier this year, Prilenia launched a phase 2 clinical trial in the US to evaluate the safety and efficacy of Pridopidine in treating Levodopa Induced Dyskinesia in patients with Parkinson’s Disease.

What is a Platform Trial?

A “platform trial” is a generic term for a randomized design with a common control arm and many different experimental arms that enter and exit the trial as futility or efficacy are demonstrated, often according to Bayesian decision rules. The trial itself then comprises a platform or standing infrastructure to which novel therapies may be added or from which they may be dropped. While biomarker cohorts in a platform trial may not be explicitly separate, the treatment effects of various experimental treatments are usually modeled as independent parameters across molecularly defined subtypes, often according to a Bayesian hierarchical model. Adaptive randomization, i.e. mid-trial shifts in the randomization ratios for patients with a given biomarker signature to favor the treatment showing the most promise in that signature, may also be present.

Who is Prilenia?

Prilenia is a clinical stage biotech startup founded in 2018 with the purpose of improving the lives of patients and their families by developing treatments for neurodegenerative and neurodevelopmental disorders. It is led by Michael Hayden, MD, PhD., together with a highly experienced team with a track record of success. Michael is the founder of five biotech companies and was previously President of Global R&D and Chief Scientific Officer at Teva. He has directed the development of multiple innovative drug products leading to 35 approvals between 2012-2018. Prilenia is based in Herzliya, Israel and in Boston, MA. Pridopidine was acquired by Prilenia from Teva in 2018 and is currently in Phase 2 clinical development for the treatment of patients with Parkinson’s Disease suffering from Levodopa Induced Dyskinesia (PD-LID). In addition to the Healey platform trial in ALS, Prilenia is planning to initiate a phase 3 trial in Huntington Disease in the near future.

Lead Research/Investigator

Merit Cudkowicz, MD, MSc, director of the Sean M. Healey & AMG Center for ALS at Mass General

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