Sarepta's shares soared Tuesday morning as it presented preliminary phase 1/2 data for potentially curative gene therapy for boys with Duchenne muscular dystrophy (DMD).
Duchenne is caused by mutations in the dystrophin gene that stop it from producing the dystrophin protein. Without it, muscle fibers, including those in the heart, eventually weaken and die. Sarepta's data, taken from just three patients, showed an increase in micro-dystrophin—a truncated version of dystrophin—significant enough that the treatment might potentially stop, or even reverse the disease's effects.
Specifically, biopsies taken three months after treatment showed the patients had "robust levels" of microdystrophin, producing 38% of the protein compared to normal. All three patients also showed "significant decreases" in their level of serum creatine kinase (CK), a biomarker linked to muscle damage caused by DMD.
Two patients had elevated levels of the enzyme gamma-glutamyl transferase, but this was addressed with steroids. No serious adverse events were reported.
“I have been waiting my entire 49-year career to find a therapy that dramatically reduces CK levels and creates significant levels of dystrophin. 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," said Jerry Mendell, of Nationwide Children's Hospital, who presented the data. "I look forward to treating more patients in the clinical study to generate the data necessary to bring this therapy to patients with DMD, with the goal of dramatically changing the course of the disease.”
Sarepta licensed the treatment, known as AAVrh74.MHCK7.micro-Dystrophin, from Myonexus in May. It uses microdystrophin rather than dystrophin as the latter is too big to fit into the delivery vector. Mendell worked on it alongside Louise Rodino-Klapac, previously Myonexus' chief scientific officer and recently tapped by Sarepta to lead its gene therapy unit.
They optimized AAVrh74.MHCK7.micro-Dystrophin for DMD—its complex-seeming name comes from the vector used to deliver it and a promoter that boosts its effects in heart muscle. AAVrh74 is an adeno-associated virus that can be delivered to skeletal, diaphragm and cardiac muscle without also crossing the blood-brain barrier.
"The MHCK7 promoter has been chosen for its ability to robustly express in the heart, which is critically important for patients with DMD, who typically die from pulmonary or cardiac complications," according to the statement.
Sarepta's first Duchenne drug, Exondys 51, squeaked past the FDA in 2016, but is only effective in the 13% of DMD patients whose disease is amenable to exon 51 skipping. With 21 programs in its pipeline, the company is working on treatments that will be more broadly usable, and those that could be one-time, curative therapies.
"Since the discovery of the dystrophin gene in 1986, scientists, clinicians, patient advocates and the biotech ecosystem have tirelessly searched for ways to restore or replace dystrophin and rescue boys with DMD from the damage and early death. Dr. Mendell’s results, if confirmed in additional patients, studies, measures and time points, represent a monumental leap forward in the direction of our goal," Ingram said.
Sarepta isn't alone in its mission. Solid Bio, which was just cleared to resume a phase 1/2 DMD trial, was also up on Sarepta's data. And Pfizer is working on its own DMD gene therapy, picked up in its $700 million buyout of Bamboo Therapeutics in 2016.