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Helixmith Reports Positive Topline Results from Phase 2A Study of ALS Treatment

September 6, 2022

Helixmith reported that topline results from a phase 2A study in individuals with the rare and fatal neurodegenerative condition amyotrophic lateral sclerosis showed its experimental therapy Engensis was safe and well tolerated.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of upper and lower motor neurons that causes progressive paralysis and eventual death due to respiratory failure.

Helixmith’s non-viral plasmid DNA product, Engensis, is designed to express recombinant HGF protein in nerve and Schwann cells to promote nerve system regeneration and induce the formation of microvascular blood vessels. HGF has a short half-life (5 minutes or less) and is quickly removed from the body by the liver, creating an obstacle to effective treatment with previous injectable recombinant HGF protein products. A single injection of Helixmith’s plasmid DNA product expresses the HGF gene at levels 30-40 times higher than conventional plasmid DNA and provides sustained gene expression in mouse models for 2 weeks, with peak protein expression at Day 7 and a gradual decrease over the next week. In addition to ALS, Engensis is being studied for painful diabetic peripheral neuropathy, diabetic foot ulcers, claudication, coronary artery disease, and Charcot-Marie-Tooth disease.

The phase 2A was a double-blind placebo controlled multi-center study involving five sites (four in the United States and one in Korea) and 18 subjects randomized to a 2:1 ratio of Engensis to placebo. In the phase 2A study, three treatments of Engensis or placebo were injected in the upper and lower limbs on months 0, 2, and 4. One treatment consisted of two cycles of injections on two-week intervals of 64 mg of Engensis or placebo in total. A total of 192 mg of Engensis was given to each subject over a four-month period. In addition, there was a follow-up period of six months after the first injection on Day 0.

The results of the study demonstrated no difference in the frequency of treatment emergent adverse reactions (TEAEs) with 83 percent for each group. One TEAE, bronchitis, was reported in the Engensis group but was determined to not be related to the study drug. Injection site reactions were reported by 50 percent of the Engensis group and by 66.7 percent of the placebo group. Most of the injection site reactions were Grade 1 or 2 and resolved within a short time, and none of the participants in the study discontinued due to the number of injections. These data suggest that high dose, repeated treatments of Engensis, were safe and well tolerated, providing a great deal of flexibility in designing dosing schemes for future clinical studies.

Given the primary endpoint of this study was to test safety and tolerability, efficacy was measured only as an exploratory parameter. ALSFRS-R scores, muscle functions using handheld dynamometry, and ALSAQ-40 were among the measurements collected. Since the study size was small and four subjects dropped out early, there was not adequate data to compare efficacy between the Engensis and placebo groups.

Author: Rare Daily Staff

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