Sponsor: Biohaven Pharmaceuticals, Inc

Overview:

Troriluzole is a third-generation prodrug of riluzole, a small molecule hypothesized to decrease over-excitability of neurons in the brain by reducing levels of free glutamate. Glutamate levels have been shown to be abnormal in the brains of patients with different types of ataxias. In addition, ataxia model systems have shown over-excitability of Purkinje cells, a type of cerebellar neuron necessary for coordinated movement. Therefore, troriluzole is hypothesized to improve coordinated movement in ataxia patients through regulating glutamate levels in the brain and thereby improving neuronal function.

Ataxia Types Included in Clinical Trials to Date:

SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10

Potential Utility in Other Ataxias (i.e. sporadic, unknown cause, other SCAs, etc,)

Yes

Current Stage of Development:

A Phase 3 clinical trial sponsored by Biohaven is ongoing and no longer recruiting. The trial has enrolled over 200 adults affected with SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA10. Topline results of this trial were reported in the first half of 2022. Read more in their press release.

Clinicaltrials.gov Reference – https://clinicaltrials.gov/ct2/show/NCT03701399

An investigator-initiated Phase 3 open-label study of trigriluzole (BHV-4157) is also ongoing in SCA1, SCA2, SCA3, and SCA6 patients who were already taking Riluzole for more than 8 weeks, and in non-genetic pure cerebellar ataxia and MSA-C patients.

Clinicaltrials.gov Reference – https://clinicaltrials.gov/ct2/show/NCT03408080

News/Press Releases:

February 25, 2022 – Biohaven announced that the company expects to report topline of troriluzole in Spinocerebellar Ataxia (“SCA”) in the first half of 2022.

March 15, 2019 – Biohaven announced that the company has initiated patient enrollment in a Phase 3 clinical trial of its third generation pro-drug troriluzole for the treatment of SCA.

October 2, 2017 – Biohaven reported negative topline results from SCA phase 2/3 trial. Patients that received Trigriluzole did not exhibit greater improvement in SARA scores than patients that received placebo (non-active drug). However, patients that received placebo exhibited a much higher “placebo response rate” than expected compared to prior randomized controlled trials in SCA meaning many patients who received a non-active drug showed an unanticipated improvement in symptoms likely due to psychological rather than physical affects.

May 30, 2017 – Biohaven announced that the company has completed enrollment in Spinocerebellar Ataxia Clinical Trial with trigriluzole.

May 15, 2017 – The Food and Drug Administration has granted Fast Track designation to trigriluzole (BHV-4157) for the potential treatment of SCA.

Results/Publications:

March 2022 – Safety and efficacy of riluzole in spinocerebellar ataxia type 2 in France (ATRIL): a multicentre, randomised, double-blind, placebo-controlled trial. In a Phase 3 trial of SCA2 only patients, riluzole did not lead to any clinical or radiological improvements in patients. Riluzole is the metabolite of troriluzole, but these are distinct candidate drugs. Therefore, lack of efficacy of riluzole doesn’t necessarily predict that troriluzole will also not be effective for treatment of SCA2 or other ataxia types.

October 2015 – Riluzole in patients with hereditary cerebellar ataxia: a randomised, double-blind, placebo-controlled trial. Results of a phase 2, randomized, double-blind clinical trial (NCT01104649) of 55 patients with either spinocerebellar ataxia showed that about half of the patients that were treated with riluzole for 1 year exhibited a decrease in SARA score, while only 11% of patients treated with placebo (non-active drug) exhibited a decrease in their SARA score. SARA SARA is a clinical test that assesses the severity of a person’s ataxia symptoms, where higher scores indicate worsening of symptoms. No severe adverse events were recorded.

Sponsor: Novartis Therapeutics

Overview: CAD-1883 is a small molecule and modulator of calcium-activated potassium ion channels. It is hypothesized to improve symptoms in patients with spinocerebellar ataxia through regulating neuronal firing of cells in the cerebellum.

Ataxia Types Included in Clinical Trials (planned):

SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA17, ARCA1

Potential Utility in Other Ataxias (i.e. sporadic, unknown cause, other SCAs, etc,)

Yes

Current Stage of Development: A Phase 2 clinical trial sponsored by Cadent Therapeutics was planned to begin in 2022 and would have included participants with SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA17, and ARCA1. However, the clinical trial was withdrawn in January 2021 following the acquisition of Cadent Therapeutics by Novartis Therapeutics. According to clinicaltrials.gov, “as part of a pipeline assessment, the Synchrony-1 trial will not proceed as initially scheduled.  

Clinicaltrials.gov Reference – https://clinicaltrials.gov/ct2/show/NCT04301284

A Phase 2 clinical trial sponsored by Cadent Therapeutics of CAD-1883 in individuals with essential tremor was completed in 2019. No serious adverse events were observed in treated patients in this study.

Clinicaltrials.gov Reference – https://www.clinicaltrials.gov/ct2/show/results/NCT03688685

News/Press Releases:

December 17, 2020 – Novartis announced that the company has entered an agreement to acquire Cadent Therapeutics. The acquisition included the CAD-1883 clinical stage program for movement disorders.

June 4, 2019 – FDA granted Orphan Drug designation to CAD-1883 (Cadent Therapeutics), an investigational treatment for spinocerebellar ataxia.

Sponsor: Sclnow Biotechnology Co., Ltd.

Overview: The purpose of this study is verify the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSC) therapy for patients with Spinocerebellar Ataxia, and in addition, explore the possible mechanisms of UC-MSC therapy in Spinocerebellar Ataxia.

Ataxia Types Included in Clinical Trials (planned):

SCA1, SCA2, SCA3, SCA6

Development Stage:
Phase 2

Clinicaltrials.gov Reference – 
https://clinicaltrials.gov/ct2/show/NCT03378414

This information was obtained from clinicaltrials.gov

Stemchymal (Allogenic Stem Cells)

Sponsor: Steminent Biotherapeutics

Overview: Stemchymal® is a formulation allogenic of stem cells isolated and cultured with from human adipose tissue.

Ataxia Types Included in Clinical Trials (planned):

SCA2, SCA3

Potential Utility in Other Ataxias (i.e. sporadic, unknown cause, other SCAs, etc,)

Yes

aCurrent Stage of Development: A Phase 2 clinical trial in SCA2 and SCA3 patients has been planned since 2018. The current status of this trial is unknown.

News/Press Releases:

July 18, 2018 – The FDA has accepted Steminent’s Investigation New Drug (IND) application of Stemchymal for the treatment of polyglutamine spinocerebellar ataxia.

Publications

Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells.

Steminent has completed a phase I/II clinical trial with Stemchymal^® for the treatment of SCA. Evidence of Stemchymal^® safety was generated in this trial with no biological-related adverse events observed in the 12-month follow up. Moreover, evidence of potential efficacy was observed in the preliminary Phase I/II data from two efficacy  assessments:  Scale for the Assessment and Rating of Ataxia (SARA) and the Sensory Orientation Test (SOT).  Sixty-six percent of the subjects showed improvement in both the SARA score and the SOT score in the first month following a single infusion of Stemchymal^®.  These measured functional improvements were maintained in study subjects for up to 6 months.

In December 2015, Steminent received US FDA Orphan Drug Designation for Stemchymal^® in the treatment of PolyQ SCAs. The US FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics intended for both safe and effective treatment of rare indications that affect fewer than 200,000 people in the U.S. The granted designation also allows Steminent to enjoy a 7-year market exclusivity upon approval of Stemchymal^® and other development incentives including tax credits for clinical research costs and Prescription Drug User Fee Act (PDUFA) fee exemption.

To further investigate the safety and efficacy of Stemchymal^® for the treatment of SCAs, Steminent is currently conducting a randomized, double-blind/placebo-controlled phase II clinical trial (NCT02540655).