Dominic Rowe, MDDominic Rowe, MD
Several new developments have been reported in the effort to identify treatment targets and therapies for amyotrophic lateral sclerosis (ALS). The latest news comes from pharmaceutical and biotech companies as well as a research collaborative and advocacy group in California, Switzerland, New York, and Pennsylvania.

Collaborative Medical Development (CMD) and AL-S Pharma AG have launched phase 1 clinical trials examining  CuATSM1 and AP-101,2 respectively, in patients with ALS, while The Association For Frontotemporal Degeneration (AFTD) and Target ALS have launched a $5M grant-making partnership with the long-term goal of identifying biomarkers and treatments.3

CMD, a clinical-stage biopharmaceutical company, will examine the tolerability and efficacy of CuATSM in patients with ALS across 4 sites in Australia over a 24-week period (NCT04082832). The first patient was enrolled in October in the multicenter, randomized, double-blinded, placebo-controlled trial.

Each patient will receive the oral agent or placebo once daily for 24 weeks, and will be evaluated based on the Revised ALS Functional Rating Scale (ASLFRS-R), Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS) score and seated slow vital capacity (SVC) at baseline and following 2, 4, and 6 cycles of treatment, in addition to safety assessments. The patients, aged 18-70 years, must not have been taking riluzole or have been on a stable dose for 4 weeks prior to the trial. The study, which has a target enrollment of 80 patients, has an estimated completion date at the end of 2020.

Dominic Rowe, MD, professor of neurology at Macquarie University and coordinating principal investigator, said, “We are excited to have enrolled the first patient in this study. Working together with our patients and the CMD team, we’re optimistic that this may be the first effective disease-modifying treatment for ALS.”1

In Switzerland, AL-S Pharma AG, a biotech company, announced the enrollment of the first patient in a phase 1 trial to evaluate AP-101 in patients with ALS (NCT03981536). AP-101, which has orphan drug designation from the FDA, EMA and Swissmedic, is a human antibody against misfolded superoxide dismutase 1 (SOD1).

“Promising preclinical data with the antibody warrant clinical development of AP-101, and we hope to provide therapeutic benefit to patients suffering with ALS,” said Michael Salzmann, CEO and COO of AL-S Pharma and Neurimmune, respectively. The company is expected to enroll 18 patients in the open-label, non-randomized trial to examine safety, tolerability, and pharmacokinetics.

Meanwhile, The Association for Frontotemporal Degeneration and Target ALS have announced a $5M multi-year, grant-making initiative with the intention of promoting collaboration between scientists from academia and the pharmaceutical/biotech industries to help discover new drug targets and candidate biomarkers that may lead to new therapeutic strategies. The partners will work together on ALS-focused projects and organize specific joint meetings for their respective scientific communities.

While all 3 endeavors are early stage, the end goal is the same: to breathe hope into the ALS community by identifying novel treatments.
REFERENCES
1. Collaborative Medical Development Enrolls First Patient in a Randomized, Placebo-Controlled Clinical Trial of CuATSM For The Treatment of Amyotrophic Lateral Sclerosis [news release]. Mill Valley, CA: Collaborative Medical Development, LLC. October 14, 2019. prnewswire.com/news-releases/collaborative-medicinal-development-enrolls-first-patient-in-a-randomized-placebo-controlled-clinical-trial-of-cuatsm-for-the-treatment-of-amyotrophic-lateral-sclerosis-300938147.html. Accessed October 16, 2019.
2. Neurimmune and TVM Capital Life Science Announce the Initiation of AL-S Pharma Phase 1 Study of AP-101 for the Treatment of ALS [news release]. Schlieren, Switzerland: Neurimmune. October 16, 2019. prnewswire.com/news-releases/neurimmune-and-tvm-capital-life-science-announce-the-initiation-of-al-s-pharmas-phase-1-study-of-ap-101-for-the-treatment-of-als-300939318.html. Accessed October 16, 2019.
3. Target ALS and AFTD Announce Groundbreaking Partnership to Spur Drug and Biomarker Development for ALS and FTD [news release]. New York, NY: The Association for Frontotemporal Degeneration. October 15, 2019. prnewswire.com/news-releases/target-als-and-aftd-announce-groundbreaking-partnership-to-spur-drug-and-biomarker-development-for-als-and-ftd-300938751.html. Accessed October 16, 2019.