Repeated Injections of ALS Gene Therapy Well-Tolerated


Although efficacy and HGF expression were assessed as outcome measures, comparisons were not able to be made between placebo and Engensis groups.

High-dose, repeated injections of Engensis, an intramuscularly delivered gene therapy developed by Helixmith, were found to be safe and well-tolerated in participants with amyotrophic lateral sclerosis (ALS) enrolled in a phase 2a trial (NCT04632225).

“Helixmith greatly appreciates the generous and eager participation of the ALS patients. Data from these results are expected to provide valuable information on the understanding of the mechanisms of actions of Engensis, and its effects on the expression of human genes, which will greatly help in the development of innovative medicines based on hepatocyte growth factor (HGF)/c-Met signaling,” the company wrote in a statement.

Engensis is a plasmid DNA therapy encoding human HGF. The multicenter, placebo-controlled, double-blind study enrolled 18 participants across 4 sites in the US and 1 in South Korea. These participants were randomized 2:1 to Engensis and placebo. Participants were then injected with Engensis or placebo 3 times in the upper and lower limbs on months 0, 2, and 4. Each treatment consists of 2 injection cycles in 2-week intervals of 4 mg of Engensis or placebo, for a total of 192 mg over a 4-month period. Trial participants were followed up for 6 months after the first injection on day 0.

The study’s primary endpoint was safety of the intramuscular injections. Investigators found that this dosing regimen of Engensis was well-tolerated, with both the placebo and Engensis groups experiencing an 83% rate of treatment-emergent adverse events (TEAEs). A TEAE of bronchitis was reported in the Engensis group but deemed unrelated to Engensis. Participants in both the Engensis (50%) and placebo groups (66.7%) experienced injection site reactions which were mostly grades 1 or 2 and quickly resolved. No participants discontinued the study due to number of injections.

READ MORE: Charcot-Marie-Tooth Gene Therapy Yields Improvements in Disability and Muscle Loss

“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,” Helixmith wrote.

The study’s planned additional outcome measures included muscle function as assessed by Revised Amyotrophic Lateral Sclerosis Function Rating scores, muscle strength assessed by Hand-Held Dynamometry and Accurate Test of Limb Isometric Strength, quality of life as assessed by ALS Assessment Questionnaire, patient and clinical reported outcomes as assessed by Patient Global Impression of Change and Clinical Global Impression of Change, respiratory function as assessed by Slow Vital Capacity and time to tracheostomy, and survival and mortality. However, the study size was small and 4 participants dropped out early, leaving investigators unable to compare efficacy between Engensis and placebo groups.

“Given the primary endpoint of this study was to test safety and tolerability, efficacy was measured only as an exploratory parameter,” Helixmith wrote.

A last outcome measure was gene expression differences in muscle atrophy biomarkers between Engensis and placebo groups as assessed by RNA sequencing methods. Investigators collected biopsy samples from participants’ injection sites, but data collected has been limited so far. Helixmith has previously observed HGF expression in animal models.

“Thanks to our dedicated clinical trial participants, muscle biopsy samples were collected during the course of the trial and will be subjected to histological and molecular biological analyses using RNA-Seq,” the company wrote.

Participants continue to be assessed in a 6-month extension, long-term safety study of Engensis (NCT05176093). The company will continue to analyze the phase 2a data. Full data readouts will be presented at a future scientific conference and the company will determine how to move forward with the therapy at that time.

Helixmith announces topline results from phase 2a study of engensis for treatment of ALS (amyotrophic lateral sclerosis). News release. Helixmith. September 6, 2022.
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