Epic Bio’s EPI-321 named FDA orphan drug for FSHD

Phase 1/2 trial of epigenetic therapy EPI-321 expected in first half of 2024

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by Andrea Lobo |

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Epic Bio’s epigenetic therapy EPI-321 has been granted an orphan drug designation by the U.S. Food and Drug Administration (FDA) as a treatment for the most common form of muscular dystrophy in adults, called facioscapulohumeral muscular dystrophy (FSHD).

The designation is given to medications that could prevent, diagnose, or treat rare diseases, which are those affecting fewer than 200,000 people in the U.S. It confers certain incentives including financial benefits and seven years of market exclusivity if the therapy is ultimately approved.

The company plans to start a Phase 1/2 clinical trial of EPI-321 in the first half of 2024. The study will assess the therapy’s safety, activity, and preliminary efficacy in people with FSHD.

“We are pleased the FDA has recognized the unmet need of those living with FSHD by granting this Orphan Drug Designation, and we believe EPI-321 could serve as an important new therapeutic option for these patients,” Weston Miller, MD, Epic Bio’s chief medical officer, said in a company press release.

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FSHD causes weakness and wasting in muscles of the face, shoulders, and upper arms. Symptoms are usually noticeable by age 20 and tend to worsen gradually over time, and can cause marked disability.

The disease is caused by mutations that abnormally activate the DUX4 gene, leading to the production of the DUX4 protein in cells where it is not normally produced. In muscle cells, the protein is toxic and eventually leads to the symptoms of FSHD.

The DUX4 gene is normally inactive because the DNA region where it is located is usually turned off due to hypermethylation, which occurs when methyl chemical groups are added to DNA and block gene activity.

EPI-321 expected to block toxic production of DUX4 protein

EPI-321 is an experimental epigenetic therapy intended to address the underlying molecular mechanisms of FSHD, by restoring methylation to the DNA region containing the DUX4 gene. This is expected to block the toxic production of the DUX4 protein in muscle cells.

Epigenetics refers to chemical modifications, like methylation, that regulate gene activity, but do not change the DNA itself.

The therapy is delivered to muscle tissue in a single administration, packaged in an adeno-associated virus, or AAV, that has been clinically validated to be delivered to muscle, according to Epic Bio. AAVs are commonly used in gene therapy because they are easy to manipulate in the laboratory, and are designed to be harmless to people.

Preclinical studies from the company have shown a single administration of EPI-321 blocked the expression (activity) of DUX4 gene in muscle cells derived from FSHD patients, and also reduced cell death.

In addition, in a mouse model of the disease, EPI-321 led to a 55% increase in the survival of skeletal muscle cells, which are those used for movement.

“We are working diligently to advance EPI-321 toward the clinic, and we look forward to generating meaningful clinical data to inform its future development as a potential new treatment for FSHD,” Miller said.