Sarepta Therapeutics Inc. (NASDAQ:SRPT) hit an all-time high Tuesday morning, adding $71.26 (68%) to $176.50 and pushing the company's market cap over $11 billion, after reporting preliminary data from a Phase I/IIa trial evaluating AAVrh74.MHCK7.micro-Dystrophin to treat Duchenne muscular dystrophy. The stock settled during afternoon trading and ended the day up $38.69 (37%) to $143.93.
In three DMD patients in the open-label, U.S. trial, the microdystrophin gene therapy led to mean sarcolemma-localized transduced microdystrophin expression, as measured by the percentage of microdystrophin-positive fibers, of 76.2% and a mean fiber intensity of 74.5% compared with normal controls. In posttreatment biopsies, Sarepta reported mean microdystrophin levels as measured by Western blot of 38.2% of normal, or 53.7% of normal adjusted for fat and fibrotic tissue. The gene therapy also reduced mean serum creatinine kinase levels by over 87% at day 60.
The company said no serious adverse events were reported in the trial, which is enrolling about 12 patients. Two patients had elevated gamma-glutamyl transferase (GGT) levels, but both cases resolved within a week with increased steroids.
Sarepta has an exclusive option to the microdystrophin gene therapy program from Nationwide Children’s Hospital. AAVrh74.MHCK7.micro-Dystrophin combines the MHCK7 promoter with the AAVrh74 adeno-associated virus (AAV) vector to deliver a microdystrophin transgene designed to maintain spectrin-like repeats 2 and 3 (see “Sarepta Discusses Exondys 51 Sales, DMD Pipeline”).
Sarepta President and CEO Douglas Ingram has told BioCentury that AAVrh74 is designed to enhance expression in muscle compared with AAV9 vector delivery (see “AA Viral Meme”).
Solid Biosciences Inc. (NASDAQ:SLDB) is developing a microdystrophin gene therapy that uses an AAV9 vector to deliver microdystrophin. The company gained $13.62 (46%) to $43 on Tuesday.
On Monday, Solid said FDA lifted a clinical hold on the Phase I/II IGNITE DMD trial of SGT-001 to treat DMD. FDA placed a full clinical hold on the trial in March after the first patient treated with SGT-001 was hospitalized due to laboratory findings of decreased platelet count followed by decreased red blood cell count, transient renal impairment and evidence of complement activation (see “FDA Lifts Clinical Hold on Solid's DMD Gene Therapy”).
Sarepta also has an option to another microdystrophin gene therapy from non-profit organization Genethon (Evry, France). That preclinical program delivers microdystrophin via an AAV2 vector (see “Sarepta Gets Option for Genethon’s DMD Gene Therapy”).