FDA Paves Way for Clinical Trials of Sarepta’s Duchenne MD Therapy SRP-5051

The U.S. Food and Drug Administration has taken a step that will allow Sarepta Therapeutics to start clinical trials of its Duchenne muscular dystrophy therapy SRP-5051.

That move was accepting the company’s Investigational New Drug application for SRP-5051. The therapy, known as a peptide phosphorodiamidate morpholino oligomer, is designed to treat those whose Duchenne MD stems from the exon 51 genetic mutation. They constitute the largest group of DMD patients — about 13 percent.

Genes are made up of dozens of components known as exons. A missing exon can lead to a gene mutation that generates a faulty protein, causing a disease.

The gene component that’s missing in Duchenne MD, exon 51, leads to an abnormal version of the dystrophin protein. SRP-5051 is designed to bridge the missing exon 51 link in the exon sequencing, producing a normal version of the protein.

The Phase 1/2a clinical trial that Sarepta plans will involve DMD patients who are missing exon 51. Results of the study will help researchers design the next clinical trial, which will focus on SRP-5051’s ability to generate dystrophin protein and improve patients’ disease. The second trial will start by mid-2018 or as soon as researchers are able to identify an optimal therapeutic dose of SRP-5051.

“DMD is a cruel and, at least today, an invariably fatal disease,” Douglas Ingram, Sarepta’s president and chief executive officer, said in a press release. The FDA’s sign-off on the Investigational New Drug application “to bring SRP-5051 to the clinic [clinical trials] is not merely a success for Sarepta,” Ingram said. “More importantly, it represents a potential approach for a better life for children living with DMD. For that reason, we intend to move urgently in further pursuit of our goal of translating promising science into potentially life-saving and life-enhancing medicines.”

Sarepta will begin enrolling patients in the trial immediately “to identify a safe and therapeutic dose of SRP-5051,” Ingram said.

The company used its next-generation peptide phosphorodiamidate morpholino oligomer — or PPMO —platform and what scientists call exon-skipping technology to skirt the exon 51 problem.

“We have crafted an ambitious strategy to sequence and rapidly advance multiple PPMO-based therapies designed to change the course of DMD,” Ingram said. “If we have positive signals in our first trial, we will explore the potential of applying our PPMO technology to a broad range of other neuromuscular diseases.”

Animals studies have shown that SRP-5051 can increase dystrophin protein production, Sarepta said.

In 2016, another Sarepta therapy, Exondys 51 (eteplirsen), became the first FDA-approved treatment targeting the underlying cause of DMD.