Engensis (VM202) is an investigational gene therapy being developed by Helixmith, formerly known as ViroMed, for the treatment of amyotrophic lateral sclerosis (ALS).
How Engensis works
ALS is characterized by the progressive loss of motor neurons, the specialized nerve cells that control voluntary muscles, resulting in muscle weakness and loss of motor control.
Engensis is a non-viral gene therapy that uses a plasmid — a small circular DNA molecule — to deliver the hepatocyte growth factor (HGF) gene directly to patients’ nerve and nerve-supporting cells.
The HGF gene provides the instructions to produce HGF, a protein involved in the formation of new blood vessels (angiogenesis), prevention of muscle shrinkage, and promotion of nerve cell survival and growth.
Notably, Engensis contains the instructions for two HGF forms, one consisting of 728 amino acids (the building blocks of proteins) and the other, known as deleted HGF, containing only 723 amino acids. A combination of both forms is believed to drive angiogenesis and nerve regeneration more effectively.
The therapy is injected directly into selected muscles to regenerate both damaged motor neurons and muscles. However, the genetic sequence in the plasmid is not introduced in the patient’s DNA, and eventually is degraded by the body, providing sustained HGF production for about two weeks.
By boosting HGF production, Engensis is thought to slow or stop ALS progression. Previous studies in mouse models of ALS showed that increasing HGF production in the nervous system lessened motor neuron degeneration and increased the mice’s life span.
Engensis in clinical trials
A Phase 1/2 clinical trial (NCT02039401) evaluated Engensis’ safety, tolerability, and preliminary effectiveness in 18 adults with ALS. Participants received weekly intramuscular injections of Engensis for four weeks — alternating between muscles of the arms and legs — and were followed for up to nine months.
Results showed that the therapy was generally safe and well-tolerated and resulted in a potentially slower disease progression relative to that previously reported for ALS patients.
These positive findings prompted Helixmith to launch the REViVALS-1A Phase 2a trial (NCT04632225) in collaboration with Worldwide Clinical Trials. The trial is evaluating the safety and effectiveness of Engensis against a placebo in up to 18 adults with ALS displaying motor symptoms in their limbs for four years or less.
Participants will be assigned randomly to receive an injection of either Engensis or a placebo, into muscles in the arms and legs. Each treatment cycle, consisting of two days of 128 injections each, spaced two weeks apart, will be repeated three times.
REViVALS-1A’s main goal is to assess the gene therapy’s safety, while secondary goals include changes in disability, motor function and strength, respiratory function, patient- and clinical-reported outcomes, survival, and quality of life.
The trial is expected to conclude by December 2022. Pending positive results, Helixmith plans to conduct an expanded Phase 2b trial to continue investigating the gene therapy.
Other information
Engensis received orphan drug designation in February 2014 and fast track designation in May 2016 by the U.S. Food and Drug Administration for the treatment of ALS; both are meant to speed its development and regulatory review.
Helixmith also is developing Engensis as a potential treatment for other diseases in which preventing neurodegeneration or promoting blood vessel formation may be beneficial. These include diabetic peripheral neuropathy, diabetic foot ulcer, coronary and peripheral artery disease, and Charcot-Marie-Tooth disease.
Helixmith is headquartered in Seoul, Korea, but clinical and developmental facilities are based in San Diego, California, and many of the company’s clinical trials are being conducted in the U.S.
Last updated: June 4, 2021
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