The first patient has been dosed with PGN-EDO51, an investigational therapy for the treatment of Duchenne muscular dystrophy (DMD) being developed by PepGen, in the ongoing phase 2 open-label, multiple ascending dose (MAD) CONNECT1-EDO51 clinical trial (NCT06079736), according to a recent announcement from the company.1 The therapy is being assessed in those with DMD who are amenable to exon 51-skipping therapy, comprising roughly 13% of the DMD patient population.
The company noted that it anticipates reading out preliminary data from the 5 mg/kg PGN-EDO51 dose level in the phase 2 trial in mid-2024. Those data should include the initial safety information, as well as exon 51 skipping and dystrophin protein production data.
The trial is seeking to enroll an estimated 10 boys aged at least 8 years with DMD to assess the safety and tolerability of PGN-EDO51, with the primary end point being adverse events (AEs) and serious AEs from baseline to week 16 of treatment. Additionally, the trial will evaluate key pharmacokinetic parameters, namely the maximum observed plasma concentration, the time to maximum plasma concentration, the terminal half-life, and the area under the curve for concentration time—all measured from baseline to week 12, after 4 monthly doses of PGN-EDO51.
“We are pleased to have dosed the first patient in our CONNECT1-EDO51 clinical trial, which marks another milestone in our commitment to developing therapies with the potential to truly improve the lives of people living with DMD. Based on the levels of exon skipping achieved following a single dose of PGN-EDO51 in our Phase 1 healthy volunteer trial, we are looking forward to our initial planned data readout in DMD patients at the 5 mg/kg PGN-EDO51 dose level for CONNECT1-EDO51 in the middle of 2024,” James McArthur, PhD, the president and CEO of PepGen, said in a statement.1
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PGN-EDO51 utilizes PepGen’s proprietary technology, called Enhanced Delivery Oligonucleotide (EDO), and is designed to skip the aforementioned exon 51 portion of the dystrophin transcript. The company noted its aims with the agent are to restore the open reading frame and enable the production of a truncated but functional dystrophin protein for patients.
In 2022, the company reported data from its phase 1 trial of PGN-EDO51, which was conducted in 32 healthy adult volunteers, which suggested that the treatment was generally well-tolerated up to a dose of 15 mg/kg.2 The starting dose of the current phase 2 MAD study will escalate from 5 mg/kg up to 10 mg/kg, with further escalation beyond that to be determined based on the evaluation of safety data from prior dose cohorts.
- PepGen's DMD therapy, PGN-EDO51, advances in phase 2 trial, with preliminary data at 5 mg/kg are expected by mid-2024, focusing on safety and exon skipping.
- PGN-EDO51 uses PepGen's proprietary EDO technology for DMD, demonstrating significant exon 51 skipping in phase 1 trials, and designed to restore dystrophin production.
- PepGen's neuromuscular disorder pipeline extends beyond DMD, with PGN-EDODM1 in phase 1 testing for myotonic dystrophy type 1, also anticipating preliminary data in 2024.
In phase 1 data, PGN-EDO51 delivered in a single dose of 10 mg/kg achieved an average level of 1.4% exon 51 skipping on day 28, with all healthy volunteers demonstrating exon skipping and a mean level of 2.0% following a single dose of 15 mg/kg. The peak level of exon 51 skipping in the 10mg/kg dose cohort at day 28 was 3.8%.2 At the time, McArthur said in a statement that “based on cross-trial comparisons with publicly available data, we believe that these results are unprecedented and reflect the highest level of DMD exon 51 skipping observed in a clinical trial following a single dose.”
This new announcement follows December news from PepGen that the first patient had been dosed in the ongoing phase 1 FREEDOM-DM1 trial, a single-ascending dose assessment of another of its EDO products, PGN-EDODM1, in patients with myotonic dystrophy type 1 (DM1).3 The trial is currently being conducted in Canada, with sites expected to open in the United States as well—a clinical hold was placed on the trial in May 2023 by the FDA, which then lifted the hold in October of the same year.4
PepGen expects to gather the preliminary data from the first dose level from the FREEDOM-DM1 trial in 2024.4 PGN-EDODM1 is an investigational peptide-conjugated ASO designed to liberate MBNL1 protein, which is sequestered in patients with DM1, and to restore functional downstream splicing, muscle, and other functions. Around 40,000 people in the United States and 70,000 in the European Union have DM1, with an average life expectancy of 45 to 60 years old.
1. PepGen Announces First Patient Dosed in CONNECT1-EDO51 Phase 2 Clinical Trial of PGN-EDO51 for Duchenne Muscular Dystrophy Patients Amenable to Exon 51 Skipping. News release. PepGen. January 8, 2024. Accessed January 18, 2024. https://investors.pepgen.com/news-releases/news-release-details/pepgen-announces-first-patient-dosed-connect1-edo51-phase-2
2. PepGen Reports Positive Data from Phase 1 Trial of PGN-EDO51 for the Treatment of Duchenne Muscular Dystrophy. News release. PepGen. September 28, 2022. Accessed January 18, 2024. https://investors.pepgen.com/news-releases/news-release-details/pepgen-reports-positive-data-phase-1-trial-pgn-edo51-treatment
3. PepGen Announces First Patient Dosed in Phase 1 FREEDOM-DM1 Clinical Trial of PGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News Release. Published December 18, 2023. Accessed January 19, 2024. https://investors.pepgen.com/news-releases/news-release-details/pepgen-announces-first-patient-dosed-phase-1-freedom-dm1
4. PepGen Inc. announces FDA has lifted the clinical hold on its investigational new drug application for FREEDOM-DM1 phase 1 study of PGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News release. PepGen. October 12, 2023. Accessed January 18, 2024. https://www.biospace.com/article/releases/pepgen-inc-announces-fda-has-lifted-the-clinical-hold-on-its-investigational-new-drug-application-for-freedom-dm1-phase-1-study-of-pgn-edodm1-for-myotonic-dystrophy-type-1-dm1-/