Struggling with a 50% drop in its valuation in the past two months, Sarepta Therapeutics Inc. has notched some much-needed positive results in an early-stage muscular dystrophy gene therapy trial, potentially calming some investors' nerves.
Following the Oct. 4 data release, Sarepta's stock was trading up 9% to $88.66 as of 12:12 p.m. ET.
The results from the three-patient, low-dose cohort of Sarepta's ongoing phase 1/2a trial in a genetic disease called limb-girdle muscular dystrophy type 2E, or LGMD 2E, demonstrated improvement in patients' muscle protein expression, function and blood enzyme levels, meeting the study's goals.
LGMD 2E is a monogenic disorder, meaning it stems from a single gene, characterized by the absence of the protein beta-sarcoglycan, which is responsible for preventing muscle damage. The disease results in muscle weakness, particularly in the pelvis, knees and shoulder-girdle, and affects patients' physical function and speech development. Death can result before age 30, according to Sarepta senior vice president of gene therapy Louise Rodino-Klapac. The disease is estimated to occur in about one in 14,500 to one in 123,000 newborns, according to Baylor Genetics.
According to Leerink analyst Joseph Schwartz, Sarepta's LGMD programs, which also include the 2D, 2C, 2B, 2L and 2A subtypes, had been "highly discounted by investors" who were previously wholly focused on the Cambridge, Mass.-based biotech's programs for the more common disorder, Duchenne muscular dystrophy.
"How times have changed," Schwartz said in a Sept. 30 note, referring to the stock's nosedive that began in August when Sarepta announced a serious patient illness in a DMD gene therapy program as well as a U.S. Food and Drug Administration rejection of its second RNA-targeting DMD therapy, golodirsen.
Sarepta has one DMD drug on the market, Exondys 51, an RNA therapy that targets a specific mutation on a portion of the DNA called exon 51. Golodirsen targets exon 53 in DMD patients.
Sarepta's LGMD programs were previously considered a "sideshow" by investors, but are now taking center stage due to disappointments in DMD. These programs could "move the needle for the stock from this lower valuation," Schwartz wrote.
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Trial results
Sarepta's LGMD 2E trial included one four-year-old participant and two 13-year-olds in the low dose cohort that reported results. The children were treated over 9 months with an infusion of the experimental gene therapy SRP-9003 (also known as MYO-101), which transfers a full-length SGCB gene coding for beta-sarcoglycan to amend patients' deficiency of the protein.
According to Rodino-Klapac, SRP-9003 achieved a mean of 51% beta-sarcoglycan positive fibers in patients, exceeding the trial's primary goal of achieving at least 20% beta-sarcoglycan.
The patients also saw an 82% mean reduction in creatine kinase levels, an enzyme found in the blood associated with muscle damage, Rodino-Klapac said during the Oct. 4 conference call. LGMD 2E patients typically have significantly elevated creatine kinase levels.
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The study included functional tests such as time to rise, climbing stairs and walk tests, in which patients recorded improvement. Typically, LGMD 2E patients see a decline across all these functions, Rodino-Klapac noted.
Rodino-Klapac and Sarepta CEO Doug Ingram noted that the two 13-year-old patients in the study were able to walk and run more quickly in a 100-meter test and get up from sitting with greater ease after treatment. LGMD 2E patients often experience significant decline from age 10 to 14.
LGMD patients consider functional improvements such as getting up from a chair or being able to pick up a backpack "really critical," Rodino-Klapac said.
"I hear that all the time from limb-girdle patients," Rodino-Klapac said. "They'll continue to stand because they don't want to sit down and get back up again."
The study also evaluated safety as a main goal. Two patients reported elevated liver enzymes due to decreased oral steroid treatment. Following supplemental steroid treatment, liver enzymes returned to baseline levels, Rodino-Klapac said.
Two patients had mild nausea within the first week of treatment, and Rodino-Klapac added that the symptoms did not correlate with the liver enzyme symptoms.
Sarepta will not look at another biopsy to evaluate muscle tissue due to ethical concerns, Ingram said. He pointed to Sarepta's preclinical models, including mice and dogs, which demonstrated SRP-9003's long-term efficacy.
The company plans to initiate a higher-dose portion of the trial next, comparing the three patients in the low-dose cohort to the high-dose cohort, which will also recruit three patients ages three to 15. The final dose for a more advanced trial that will potentially support drug approval, the design of which will be discussed with regulatory agencies, will be determined based on the dosing studies.
Ingram said Sarepta already has the clinical supply for the study, and the company is currently screening patients.
"Conventional wisdom says focus on function. But I would remind you this is a monogenetic disease that results from lack of protein, and that is the only reason these children are degenerating and die," Ingram said.
Ingram added that the high-dose cohort will, like the low-dose cohort, require LGMD patients to be able to move about and walk. But Sarepta intends to find a drug development pathway that allows the inclusion of nonambulatory patients in the future, first with type 2E and then with the rest of the LGMD programs.


In gene therapy, a viral vector delivers the genetic material of interest to the host cell.