Sarepta Therapeutics Stock Climbed 80% on Spectacular DMD Therapy Update

Sarepta Therapeutics shares rocketed by as much as 80 percent yesterday after the company released interim data on its experimental gene therapy AAVrh74.MHCK7.micro-Dystrophin for Duchenne muscular dystrophy (DMD).

DMD is a muscle wasting disease caused by mutations in the dystrophin gene. It is a progressive disease that usually causes death in early adulthood, with serious complications that include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 or 5,000 male children.

At its research-and-development event, the company announced that its new gene therapy, AAVrh74.MHCK7, increased production of a shortened version of the dystrophin protein in three boys with DMD. Post-treatment biopsies indicated they were producing a mean level of micro-dystrophin that was 38.2 percent compared to normal at three months, using Sarepta’s Western blot method. Using a method developed at Nationwide Children’s Hospital that corrects for readings in fat and scar tissue, the mean level was 53.7 percent compared to normal.

Doug Ingram, Sarepta’s chief executive officer, stated that, “since the discovery of the dystrophin gene in 1986, scientists, clinicians, patient advocates and the biotech ecosystem have timelessly searched for ways to restore or replace dystrophin and rescue boys with DMD from the damage and early death.” He added that the findings, “if confirmed in additional patients, studies, measures and time points, represent a monumental leap forward in the direction of our goal.”

This is a slightly different approach than the company’s Exondys 51, which was approved after a dramatic, roller-coaster regulatory process in September 2016. The dystrophin gene is the largest gene in the human genome. As a result, it is too large for the typical gene therapy approach that utilizes adenoviruses to deliver the replacement genes. The gene is involved in muscle development and function.

Exondys 51is approved for DMD patients with a specific gene mutation in exon 51 in the DMD gene. This results in a shift in what is called the gene’s reading frame, causing a malfunctioning dystrophin protein. The gene-skipping approach “skips” the deletion, allowing for the production of a shortened but still functional dystrophin protein.

Patients with mutations between exons 18 and 58 make up between 60 and 70 percent of DMD patients, and are potential candidates for AAVrh74.MHCK7, which is being evaluated in a Phase I/IIa trial. It is also gene-skipping therapy, but apparently works more broadly than Exondys 51.

In addition to showing increased dystrophin levels in the three patients reported, it also resulted in an average reduction of more than 87 percent in creatine kinase levels on day 60. Creatine kinase is an enzyme observed within muscle cells caused by damage to the muscle, and which can leak into the bloodstream. Increase creatine kinase levels are an indicator of DMD.

“I have been waiting my entire 49-year career to find a therapy that dramatically reduces CK levels and creates significant levels of dystrophin,” said Jerry Mendell, lead investigator with Nationwide Children’s Hospital, in a statement. “Although the data are early and preliminary, these results, if they persist and are confirmed in additional patients, will represent an unprecedented advancement in the treatment of DMD. I look forward to treating more patients in the clinical study to generate the data necessary to bring the therapy to patients with DMD, with the goal of dramatically changing the course of the disease.”

Although stock did eventually drop by the end of trading yesterday, it was still up by about 36.7 percent. Joseph Schwartz, an analyst with Leerink Partners, said the data “should position Sarepta as the leader in this field.”

Brian Skorney, an analyst with Baird, stated that, “given today’s data, it is really hard to believe this study won’t be positive, ushering in a new paradigm that we expect will transform outcomes for patients diagnosed with this horrible disease.”