PF-06939926 Continues to Show Safety and Efficacy in Duchenne Muscular Dystrophy


An update on the phase 1b study of Pfizer’s investigational DMD treatment was presented at the MDA 2021 conference.

Beth Belluscio, MD, PhD, executive director and global clinical lead, Pfizer

Beth Belluscio, MD, PhD

An update of data on the ongoing, multicenter, open-label phase 1b study of PF-06939926 (NCT03362502) suggest that the treatment continues to show efficacy with an acceptable safety profile in boys with Duchenne muscular dystrophy (DMD). 

The update was presented at the Muscular Dystrophy Association’s (MDA) Scientific and Clinical Conference 2021, March 15-18, by first author Beth Belluscio, MD, PhD, executive director and global clinical lead, Pfizer.

“Based on data from this cohort, we're now excited to advance our program in 2 important ways. We've expanded the phase 1b study into the non-ambulatory DMD population, and we're the first to investigate gene therapy in this population... After the phase 1 study we anticipate starting a much larger phase 3 randomized control trial in non-ambulatory patients,” Belluscio said during her presentation.

The gene therapy PF-06939926 consists of the adeno-associated virus serotype 9 (AAV9) and mini-dystrophin gene. The phase 1b study aims to evaluate the safety and tolerability of PF-06939926 in boys with DMD, as well as assess exploratory measures evaluating muscle health and ambulatory function. Researchers looked to assess primary endpoints such as adverse events (AEs), abnormal laboratory results, and other safety measures, as well as exploratory efficacy endpoints such as change from baseline on NorthStar Ambulatory Assessment (NSAA) score and other functional measures.

READ MORE: SGT-001 Shows Improvements in Key DMD Measures, Microdystrophin Expression

The study has dosed 19 participants so far. The participants are ambulatory boys with a genetic diagnosis of DMD receiving a stable, daily regimen of glucocorticoids. The participants had a median age of 8 years at screening (range, 6-12), with 12 (63%) older than 8 years of age. The low-dose cohort has 3 participants, and the high-dose (2 x 1014 vg/kg) has 16. The median NSAA score was 27 (range, 17-32).

Serious AEs (SAEs), including 1 case of dehydration and 2 relating to complement activation (acute kidney injury and thrombocytopenia) occurred in 3 participants and resolved within 3 weeks. No further SAEs occurred in the following 10 participants dosed after a mitigation plan was implemented including increased glucocorticoids after the third SAE. 

AEs occurred in over 30% of the high-dose cohort. These included vomiting, fever, thrombocytopenia, nausea, decreased appetite, fatigue, and headache.

Belluscio and colleagues made several observations regarding platelets and liver enzymes. A decrease in platelets follows a consistent pattern, with lowest levels at 10 days after treatment. On average, levels decreased to 127 x 103/µL, although declinations varied. Less than 50% of reductions were reported as an AE.

Elevated liver enzymes were noted in 2 participants as measured by glutamate dehydrogenase (GLDH). These levels were not affected by muscle disease. Elevations were noted at week 4, and gamma glutamyl transferase was slightly elevated in parallel. No abnormalities were seen in bilirubin or synthetic function, and GLDH returned to normal range within 15 days of a temporary glucocorticoid increase. 

Belluscio and colleagues also assessed external controls from 2 completed studies to analyze the natural course of DMD progression and found that 6-to-12-year-old boys with DMD from those studies experienced a median decline of 4 points on the NSAA from baseline after an initial net increase prior to 5 years of age during which motor development outpaced decline. Of the control participants aged 6-to-12 years, 70% had declining scores. Meanwhile, patients dosed with PF-06939926 in the phase 1b study mostly fell outside the bootstrap distribution of mean disease progression.

“We all recognize that function is really the ultimate goal of gene therapy, as is any therapeutic being developed for these rare diseases. It's really what matters, ultimately, to patients and their families. What has also become clear in the Duchenne field is how important it is to understand the natural history of disease, using the clinical endpoints that are used in studies,” Belluscio said.

For more coverage of MDA 2021, click here.

Belluscio B, Beaverson K, Garnier N, et al. Safety and efficacy of PF-06939926 gene therapy in boys with Duchenne muscular dystrophy: Update on data from the phase 1b study. Presented at MDA Clinical and Scientific Conference 2021; March 15–18. Poster 77.
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