Investigational DMD Gene Therapy Reports Positive Preliminary Results in Phase 1b


PF-06939926 is a recombinant adenoassociated virus serotype 9 (AAV9) capsid carrying mini-dystrophin, a shortened version of the human dystrophin gene, under the control of a muscle-specific promoter.

Dr Seng Cheng

Seng Cheng, PhD, senior vice president and chief scientific officer, rare disease research unit, Pfizer

Seng Cheng, PhD

Recently, Pfizer presented data from a phase 1b clinical trial of PF-06939926, an investigational gene therapy designed to treat Duchenne muscular dystrophy (DMD) at the 25th Annual Parent Project Muscular Dystrophy (PPMD) Connect Conference in Orlando, Florida.

The data, which are preliminary, show that at 2 months post-dosing, there are detectable mini-dystrophin immunofluorescence signals with the therapy. An average of 38% positive fibers were collected from those who were administered PF-06939926 at 1E14 vg/kg and a mean of 69% positive fibers were taken from participants who received PF-06939926 at 3E14 vg/kg.

“Gene therapy for single-gene disorders is at a formative stage in its evolution, and the initial data we’ve seen in our study for Duchenne muscular dystrophy may exemplify the potential for this modality to change patients’ lives,” said Seng Cheng, PhD, senior vice president and chief scientific officer, rare disease research unit, Pfizer, in a statement. “We are looking forward to building on these initial data and advancing the development of this therapeutic modality.”

The study’s primary end point is to assess the safety and tolerability of PF-06939926, and secondary end points included measurements of expression of mini-dystrophin distribution within muscle fibers by immunofluorescence and concentration by liquid chromatography-mass spectrometry (LCMS). PF-06939926 is a recombinant adenoassociated virus serotype 9 (AAV9) capsid carrying mini-dystrophin, a shortened version of the human dystrophin gene, under the control of a muscle-specific promoter. Pfizer noted that the AAV9 capsid was selected due to its potential to target muscle tissue.

Using the FDA-reviewed LCMS assay, normal concentrations of dystrophin were deemed to have a mean concentration just below 3000 fmol/mg of protein, while levels in the individual samples differed from the mean approximately 50 to 150%. All 6 of the study participants showed a 300- to 1800-fmol/mg of protein range, translating to 10% to 60% of normal. At 1E14 vg/kg, mean expression of mini-dystrophin was 23.6%, and at 3E14 vg/kg, was 29.5%.

Despite the exploratory nature of the functional evaluations, there were preliminary results available for 2 patients with ≥1 year of follow-up, both of whom were administered PF-06939926 at 1E14 vg/kg. They showed mean increases of 4.5 points from baselines of 24 and 25 in NorthStar Ambulatory Assessment (NSAA) scores at 12 months.

“The emerging field of gene therapy has collaboration at its core as patients, scientists, clinicians, regulators, and payors all need to come together to share their experiences,” said Debra Miller, CEO and founder, CureDuchenne, in a statement. “Without that collaboration, we wouldn’t have made the progress in our community’s understanding of the science that we’re proud is being presented today.”

The safety data show that the most common adverse events (AEs) associated with the therapy were nausea, vomiting, decreased appetite, tiredness, and fever, which were reported by 4 of the 6 study patients. A single patient with nausea and vomiting was hospitalized for intravenous antiemetics and replacement fluids, but all instances resolved within 2 to 5 days. All other AEs were resolved within 1 to 3 weeks.

Additionally, all participants reported immune responses, as anticipated, which varied in their specificity and magnitude as measured by neutralizing antibody levels and T-cell responses on the enzyme-linked immune absorbent spot (ELISPOT). Of the 6 participants, 1 developed a rapid antibody response associated with acute kidney injury, hemolysis, and a reduced platelet count. That subject was admitted to a pediatric intensive care unit and was administered intermittent hemodialysis, as well as 2 intravenous doses of a complement inhibitor, and was ultimately discharged after 11 days. Renal function returned to normal within 15 days. No other immune-related clinical events were observed.

Pfizer also announced that while it continues to collect open-label study data in boys with DMD, it is planning for a global, randomized, placebo-controlled phase 3 study, which is expected to begin in the first half of 2020. It will utilize commercial-scale manufacturing processes using multiple 2000-liter bioreactors, and “intends to leverage the learnings from the ongoing phase 1b study in order to inform Pfizer’s decisions regarding the optimal dose, assay, method of administration, concomitant medications, participant selection and safety monitoring.”


Pfizer Presents Initial Clinical Data on Phase 1b Gene Therapy Study for Duchenne Muscular Dystrophy (DMD) [press release]. New York, NY: Pfizer; Published June 28, 2019. Accessed July 1, 2019.

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