Press release from Pfizer about gene therapy

Pfizer’s new phase 1b results of gene therapy in ambulatory boys with Duchenne muscular dystrophy (DMD) support advancement into pivotal phase 3 study

Read the press release here.

Friday, May 15, 2020
Pfizer Inc. announced updated Phase 1b clinical data on PF-06939926, an investigational gene therapy being developed to treat Duchenne muscular dystrophy (DMD). The preliminary data from 9 ambulatory boys with DMD, aged 6 to 12 indicate that the intravenous administration of PF-06939926 was well-tolerated during the infusion period, with encouraging efficacy and manageable safety events, even when considering those adverse events that were more severe in nature. The treatment provided durable and statistically significant improvements across multiple efficacy-related endpoints measured at 12 months post-infusion, including sustained levels of mini-dystrophin expression and improvements on the North Star Ambulatory Assessment (NSAA) rating scale, which is a validated measure of muscle function. Three serious adverse events (SAEs) were recorded, two of which reflected likely complement activation. While these two SAEs were severe in nature, all three events fully resolved within 2 weeks, providing encouragement that close monitoring and early intervention can help mitigate the effects of complement activation. This new dataset, which includes updated 12-month results on safety, dystrophin expression, and exploratory functional endpoints for 3 additional boys, was presented for the first time during a virtual oral session at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting.


Seng Cheng, Ph.D., Chief Scientific Officer, Pfizer Rare Disease Research Unit – “Based on the encouraging preliminary efficacy data and manageable safety events from our Phase 1b study, we believe we may have a potential breakthrough therapy for boys with Duchenne muscular dystrophy, a devastating disease for which there remains a significant medical need. We are advancing our Phase 3 program as quickly as possible and plan to begin dosing patients in the second half of 2020 pending regulatory approval. Our program has the potential to be the first DMD gene therapy Phase 3 trial start using a commercial-scale manufacturing process. If the program is successful, this manufacturing capability is expected to help position us to deliver this medicine to patients quickly following regulatory approval.”


Preliminary Safety Results

The primary endpoint of the Phase 1b study is to assess the safety and tolerability of this investigational gene therapy in ambulatory boys with Duchenne muscular dystrophy through 12 months following treatment. Based on the data to date, the most common adverse events (AEs) suspected to be related to PF-06939926 (occurring in >40% of patients) were vomiting, nausea, decreased appetite, and pyrexia (fever). There was no evidence of clinically relevant anti-dystrophin responses or hepatic dysfunction with the protocol-defined daily glucocorticoid regimen. Continue reading here.

Results from Secondary and Exploratory Endpoints

Secondary endpoints of the clinical study included measurement of mini-dystrophin concentration by liquid chromatography-mass spectrometry (LCMS) and distribution within muscle fibers by immunofluorescence.

Read more about: dystrophin concentration, dystrophin distribution and the functional assessment here.


Seng Cheng, Ph.D., Chief Scientific Officer, Pfizer Rare Disease Research Unit – “Taken together, we believe these data support the view that administration of PF-06939926 at a dose of 3E14 VG/kg can lead to the expression of potentially therapeutic levels of mini-dystrophin that may translate to a measurable improvement in muscle function and health in DMD patients. We also want to give our heartfelt thanks to all the patients, their families, the researchers, investigators, other clinicians and advocacy organizations for their passion, expertise and engagement in helping to advance clinical research and care for the Duchenne muscular dystrophy community.”


About PF-06939926

PF-06939926 is an investigational, recombinant adeno-associated virus serotype 9 (AAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. The AAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue. Pfizer initiated the Phase 1b multi-center, open-label, non-randomized, ascending dose study of a single intravenous infusion of PF-06939926 in 2018. The goal of the study is to assess the safety and tolerability of this investigational gene therapy. Other objectives of the clinical study include measurement of dystrophin expression and distribution, as well as assessments of muscle strength, quality and function.


About Pfizer

Pfizer’s innovative portfolio focuses on the discovery and development of new medicines and vaccines. By focusing on the best science and patient experience, Pfizer’s leadership and significant investments support faster delivery of breakthrough medicines that can fulfill unmet needs.

Interesting link

La Fondation La Force talks with Dr. Jeffrey Chamberlain, a geneticist at the University of Washington, Seattle, about adenovirus-associated (AAV) micro-dystrophin gene replacement therapy.

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