Shares in Sarepta Therapeutics surged as much as 80 percent Tuesday after the company released preliminary data at an investor event from a Phase I/IIa trial showing that its experimental gene therapy, dubbed AAVrh74.MHCK7, boosted production of a truncated form of a muscle-making protein in three young boys with Duchenne muscular dystrophy (DMD). Specifically, the company reported that all post-treatment biopsies showed that at three months, the patients were producing a mean level of micro-dystrophin that was 38.2 percent compared to normal, when measured using Sarepta’s Western blot method, or 53.7 percent compared to normal, based on a method developed at Nationwide Children’s Hospital that corrects for readings in fat and scar tissue.

Sarepta CEO Doug Ingram stated that “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.” 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.”

Four boys between the ages of four and seven years old have so far been given the single-infusion treatment, although data were available on three of the patients. Sarepta said other preliminary results from the trial showed that mean gene expression, as measured by percentage of micro-dystrophin positive fibres, was 76.2 percent compared to normal control, while all patients showed significant decreases of serum creatine kinase (CK), an enzyme associated with muscle damage, with a mean CK reduction of over 87 percent at day 60. The level of CK decline in the patients indicates “how much the micro-dystrophin that we’re seeing is protecting the muscle fibers,” explained principal investigator Jerry Mendell.

Sarepta said no serious adverse events were observed in the study. The company noted that two patients saw their levels of gamma-glutamyl transferase rise, but the issue was resolved with increased steroids within a week and returned to baseline levels, while patients also had transient nausea tied to steroid dosing.

Commenting on the news, Baird analyst Brian Skorney said “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.” Analyst Joseph Schwartz of Leerink Partners suggested the results “should position Sarepta as the leader in this field.” He also expressed confidence that the data would likely translate to functional improvements.

Sarepta plans to report more detailed data from all six patients enrolled in this part of the study at the World Muscle Society (WMS) conference in October. According to Ingram, the company intends to initiate another study in which 24 boys with DMD will be assigned to treatment with AAVrh74.MHCK7 or placebo for one year, after which boys in the placebo arm will also receive the gene therapy. The CEO said the hope is for Sarepta to be able to file for FDA approval off of that data, but “we need to meet with the FDA and ensure it aligns with us on that process.” He indicated that the drugmaker plans to meet with the agency within four months to discuss the path toward approval.

Sarepta gained accelerated FDA approval for its once-weekly intravenous therapy Exondys 51 (eteplirsen) in 2016 for DMD patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. The company has said that patients with mutations between exons 18 and 58, or approximately 60 percent to 70 percent of the DMD population, are potential candidates for AAVrh74.MHCK7. Meanwhile, Sarepta recently disclosed a negative trend vote by regulators in Europe in regards to approval of Exondys 51 for patients with DMD (for related analysis, see ViewPoints: Sarepta builds out platform as EU opportunity shrinks). The drugmaker, which also expanded its partnership last month with Invitae focused on DMD research, unveiled plans in March to complete its rolling submission by the end of the year seeking US approval of its investigational DMD treatment golodirsen to treat patients with exon 53-skipping genetic mutations.

Meanwhile, shares in Solid Biosciences jumped as much as 82 percent Tuesday, the day after the company announced that the FDA lifted a clinical hold on its experimental micro-dystrophin gene transfer SGT-001. The hold was placed in March after the first patient who had been given SGT-001 had to be hospitalised for low platelet and red blood cell counts. The FDA cleared Solid Biosciences to resume testing of its gene therapy in the Phase I/II IGNITE DMD study with a modified protocol that includes closer monitoring.