New milestones hit in MD trial testing treatment to turn off faulty gene
Early data showing evidence of safety, effectiveness of targeted gene therapy
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Two major steps are now complete in an early clinical trial testing a one-time epigenetic therapy — a treatment designed to turn on or off a specific gene without changing the underlying DNA — for facioscapulohumeral muscular dystrophy (FSHD), a genetic disease that characteristically affects the muscles of the face, shoulders, and upper arms.
Epicrispr Biotechnologies announced that its first trial testing EPI-321, which targets the underlying cause of this form of muscular dystrophy, is fully enrolled, and dosing of participants is now also done.
“Completing enrollment and dose escalation marks an important milestone for the EPI-321 program,” Amber Salzman, PhD, CEO of Epicrispr, said in a company press release that also provided interim data from the trial.
The Phase 1/2 study (NCT06907875), which launched last year, has enrolled 12 adults with FSHD, and all participants have received a single infusion of the experimental treatment, according to Epicripr. Six participants received a low dose of 20 trillion vector genomes per kilogram of body weight (vg/kg), while the other six were given a higher dose of 40 trillion vg/kg. One vector genome is basically one particle of the epigenetic therapy.
The data shared to date showed that the FSHD treatment candidate “demonstrated a favorable safety profile and early evidence of disease modification,” according to Epicrispr. The company said it plans to share its findings at a conference later this year.
FSHD is marked by abnormal activity of the DUX4 gene in muscle cells, because a protein of the same name is produced when it shouldn’t be. This leads to muscle weakness primarily affecting the upper parts of the body, with problems typically seen in eye and mouth movements.
EPI-321 aims to use epigenetics — molecular modifications to DNA that change whether a gene is active without altering the underlying genetic code — to turn off the overactive gene, thus addressing the root cause of the disease. This is somewhat different from traditional gene therapy, which attempts to alter the actual DNA sequence, and not just how a gene is read.
The experimental treatment delivers its payload using a viral vector, which is essentially a virus that’s been modified to deliver genetic material instead of causing infection. The vector used in EPI-321 is specifically derived from adeno-associated virus (AAV).
Trial studying effects of FSHD treatment over 5 years
Salzman noted that this is the first study testing the treatment in FSHD patients.
“We completed enrollment [in the Phase 1/2 trial] as rapidly as the study protocol allowed in this complex first-in-human AAV gene therapy trial,” Salzman said. The trial has seven locations in the U.S., Australia, and New Zealand.
Its main goal is to assess the safety profile of EPI-321 for as long as five years. The study also aims to preliminarily assess the therapy’s biological activity and clinical effects.
Epicrispr last month announced interim data from three patients in the low-dose group who had been followed for six months after treatment with EPI-321. Imaging data showed all three experienced increases in lean muscle mass in the months following treatment. Individual gains ranged from approximately 0.5 to 1.3 pounds of muscle, and some individual muscles increased 15% in lean muscle volume, the company said.
These gains in muscle mass are a notable contrast to the typical progression of FSHD, in which patients usually lose muscle mass over time as the disease progresses.
In addition to this benefit, the first three patients also showed improvements in measures of strength and functionality at three months. These data “provide encouraging early evidence that EPI-321 may modify the underlying biology of FSHD,” Salzman said.
Epicrispr also said that biomarker data from these participants suggest that EPI-321 is silencing the DUX4 gene as intended. Further, per the company, the therapy’s safety profile has so far been manageable, with no serious side effects reported to date.
“We look forward to presenting additional clinical data at the World Muscle Society Annual Congress in September and completing 12-month follow-up across all participants next year,” Salzman said.
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