RARE Daily

FDA Grants Rare Pediatric Disease Designation to PepGen’s Therapeutic for DMD

March 13, 2024

Rare Daily Staff

The U.S. Food and Drug Administration granted both orphan drug and rare pediatric disease designations for PGN-EDO51, PepGen’s experimental oligonucleotide therapeutic for Duchenne muscular dystrophy patients whose mutations are amenable to an exon 51 skipping approach.

Duchenne muscular dystrophy (DMD) is an X-linked recessive, progressive, muscle-wasting disease predominantly affecting males that is caused by genetic mutations in the gene encoding dystrophin, a protein necessary for normal muscle function. It is one of the most prevalent rare genetic diseases, with an incidence rate of approximately one in every 3,500 to 5,000 male births. DMD is characterized by progressive muscle weakness, which leads to patients losing the ability to walk, a loss of upper body function, cardiac issues and difficulties breathing. DMD is invariably fatal by young adulthood. Despite significant advances in treatments for this devastating disease, current exon skipping therapies are thought to have limited impact on disease progression due to low levels (<5 percent) of dystrophin production.

PepGen is evaluating PGN-EDO51 for the treatment of DMD in the ongoing CONNECT1 phase 2 trial, and expects to begin enrolling patients in the CONNECT2 phase 2 trial later this year.

“Receiving these FDA designations for PGN-EDO51 emphasizes the critical demand for novel and enhanced therapeutic options for people living with DMD,” said James McArthur, president and CEO of PepGen. He said the company expects to report preliminary data from its ongoing phase 2 study this year.

PGN-EDO51 utilizes the company’s proprietary Enhanced Delivery Oligonucleotide technology to deliver a therapeutic oligonucleotide that is designed to target the root cause of this devastating disease. PGN-EDO51 is designed to skip exon 51 of the dystrophin transcript, an established therapeutic target for approximately 13 percent of DMD patients, thereby aiming to restore the open reading frame and enabling the production of a truncated, yet functional dystrophin protein.

In preclinical studies, PepGen observed that administration of PGN-EDO51 to nonhuman primates resulted in greater levels of exon-skipping when compared in head-to-head studies against a molecule that we believe is structurally equivalent to the most clinically-advanced peptide-conjugated oligonucleotide therapeutic candidate. Higher levels of exon skipping may translate to higher levels of dystrophin production in patients. PGN-EDO51 also exhibited the highest level of exon 51 skipping in nonhuman primate skeletal muscles, including the diaphragm, reported for any approved therapeutic or known development candidate at tolerable target dose levels, based on cross-trial comparisons of publicly available data.

In a phase 1 healthy volunteer single ascending dose study, PGN-EDO51 exhibited six-times higher mean exon 51 skipping than the naked oligonucleotide based on cross-trial comparisons of publicly available data.

The FDA grants orphan designation to advance the evaluation and development of new treatments intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States. Under the Orphan Drug Act, the FDA may provide sponsors incentives including tax credits for qualified clinical trials, FDA user-fee benefits, and seven years of market exclusivity in the United States after approval.

The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years. Under the Rare Pediatric Disease program, the FDA may award priority review vouchers to sponsors who have been granted rare pediatric disease designation for its drug. A sponsor who has been granted the designation and receives an approval for a drug for a rare pediatric disease may qualify for a voucher that can be sold or redeemed to receive a priority review of a subsequent marketing application for a different product.

Photo: James McArthur, president and CEO of PepGen

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