Engensis Gene Therapy Found Safe in Small Phase 2a Trial
Helixmith's therapy has potential to promote nerve cell and muscle regeneration
Repeated muscle injections with Engensis (VM202), Helixmith’s investigational non-viral gene therapy, were generally safe and well-tolerated in people with amyotrophic lateral sclerosis (ALS), according to top-line data from a Phase 2a clinical trial.
While the sample size was too small to determine the therapy’s efficacy, muscle biopsies were collected and will be examined to further evaluate the underlying mechanisms of Engensis.
“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 stated in a company press release.
Trial analysis will continue once the full dataset is available, and the company plans to present such findings at a future conference. The next steps for Engensis’ development will be determined at that time.
Engensis is a non-viral gene therapy that uses Helixmith’s proprietary small circular DNA molecule to deliver the hepatocyte growth factor (HGF) gene to cells in the muscle environment.
HGF provides instructions to produce a protein of the same name that helps the body form new blood vessels, prevents muscle loss, and promotes the growth and survival of nerve cells. The therapy is delivered via intramuscular (into-the-muscle) injections.
Helixsmith believes that by increasing HGF production, Engensis has the potential to promote nerve cell and muscle regeneration, thereby countering the progressive loss of motor control that characterizes ALS.
The therapy has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration, both of which are intended to speed its clinical development and regulatory review.
A previous open-label Phase 1/2 trial (NCT02039401) found that four once-weekly intramuscular injections of Engensis (to a total dose of 64 mg) were safe and well-tolerated among 18 ALS patients. Signs that the therapy could slow disease progression were also observed.
REViVALS-1A trial monitored 18 ALS patients over six months
These promising findings prompted the launch of a placebo-controlled Phase 2a trial, called REViVALS-1A (NCT04632225), which began patient enrollment last year. A total of 18 ALS patients experiencing motor symptoms in their limbs for four years or less were recruited at four sites in the U.S. and one in Korea.
Participants were randomized in a 2:1 ratio to receive three cycles of either Engensis or a placebo: at study’s start, at two months, and at four months. Each cycle consisted of two days of injections to upper and lower limb target muscles, spaced two weeks apart (64 mg total of Engensis or a placebo).
This meant that Engensis-treated patients received a total of 192 mg of medication over the four-month period. All participants were monitored for six months from the study’s start.
The trial’s main goal was to assess the safety and tolerability of Engensis, while efficacy measures were included as exploratory outcomes. These included changes in disability, muscle and lung function, survival, ALS-specific health-related quality of life, and the levels of muscle shrinkage biomarkers.
Top-line data showed that the investigational treatment was generally safe and well-tolerated, with no difference in the frequency of adverse events observed between the Engensis and placebo groups (83% for each).
One case of bronchitis — a condition characterized by inflammation in the main airways of the lungs due to infection — was observed in the Engensis group but was determined unrelated to treatment.
Injection site reactions were reported by 50% of Engensis-treated patients and 66.7% of those in the placebo group. Most of these reactions were mild or moderate in severity and temporary; no participant discontinued treatment due to the number of injections.
According to Helixmith, efficacy was unable to be evaluated due to the fact that four participants dropped out early from the small study.
Still, muscle tissue biopsies were obtained from injection sites to undergo analyses of muscle atrophy (shrinkage) biomarkers and others.
Since data on Engensis’ underlying mechanisms have been largely based on animal models, these results “are expected to provide valuable information on the understanding of the mechanisms of actions of Engensis, and its effects on the [activity] of human genes, which will greatly help in the development of innovative medicines,” the company stated in the release.
“Helixmith greatly appreciates the generous and eager participation of the ALS patients,” the company added.
Engensis is also being investigated across a range of conditions associated with deficits in circulation, and nerve and/or muscle damage, such as diabetic neuropathy, coronary artery disease, and Charcot-Marie-Tooth disease.
More than 500 patients have been treated with Engensis to date across 10 clinical trials and six different diseases, according to Helixmith. Data from these studies have also supported the therapy’s favorable safety profile and its ability to increase HGF production.