Pfizer Announces Positive Phase 1b Results for DMD Gene Therapy PF-06939926, Pivotal Global Phase 3 Trial Expected to Begin in Second Half of the Year

On May 15, Pfizer announced that its investigational gene therapy, PF-06939926, demonstrated favorable tolerability, encouraging efficacy, and manageable safety events in a Phase 1b clinical trial for the treatment of patients with Duchenne muscular dystrophy (DMD). The company plans to initiate global Phase 3 clinical trials of this gene therapy in the second half of this year.

Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder caused by mutations in the gene on the X chromosome that encodes dystrophin. The absence or defect of dystrophin leads to chronic muscle damage during contraction, triggers inflammatory responses, and impairs muscle regeneration. Ultimately, muscle tissue is replaced by scar tissue or fat. Symptoms of muscle weakness become apparent at age 2–3 years. As muscle tissue and function continue to decline, patients are typically confined to a wheelchair by age 12, require assisted ventilation by age 20, and often die prematurely in their 30s or 40s due to respiratory or cardiac failure.

PF-06939926, developed by Pfizer, is an investigational intravenous gene therapy. It consists of a “mini-dystrophin” transgene controlled by a human muscle-specific promoter, packaged within an adeno-associated virus serotype 9 (AAV9) vector. The AAV9 viral vector has the capacity to target and deliver the transgene to muscle tissue. This investigational therapy has been granted orphan drug status and Rare Pediatric Disease designation by the U.S. Food and Drug Administration (FDA).

In this Phase 1b study, nine patients aged 6 to 12 years with Duchenne muscular dystrophy (DMD) received treatment with PF-06939926. After 12 months of treatment, patients demonstrated durable and statistically significant improvements, including sustained levels of micro-dystrophin expression (assessed by liquid chromatography-mass spectrometry and immunofluorescence staining) and improved scores on the North Star Ambulatory Assessment (NSAA), a validated measure of muscle function.

▲ Gene therapy at different doses significantly increased dystrophin levels in muscle biopsy tissues (using fluorescence staining) (Image source: Reference [2])

“Based on the encouraging preliminary efficacy data and the manageable safety events observed in our Phase 1b study, we believe that PF-06939926 has the potential to become a breakthrough therapy for patients with Duchenne muscular dystrophy (DMD),” said Dr. Seng Cheng, Chief Scientific Officer of Pfizer’s Rare Disease Research Unit. “We are advancing PF-06939926 into Phase 3 clinical trials as quickly as possible, with patient dosing planned to begin in the second half of 2020. Our program has the potential to be the first Phase 3 trial of a DMD gene therapy conducted using commercial-scale manufacturing processes. If successful, this manufacturing capability is expected to enable us to rapidly deliver the therapy to patients following regulatory approval.”

References:

[1] Pfizer’s New Phase 1b Results of Gene Therapy in Ambulatory Boys with Duchenne Muscular Dystrophy (DMD) Support Advancement into Pivotal Phase 3 Study . Retrieved 2020-05-15, from https://www.pfizer.com/news/press-release/press-release-detail/pfizer_s_new_phase_1b_results_of_gene_therapy_in_ambulatory_boys_with_duchenne_muscular_dystrophy_dmd_support_advancement_into_pivotal_phase_3_study

[2] Analyst and Investor Call to Review DMD Gene Therapy Presentation at ASGCT. Retrieved May

, from https://s21.q4cdn.com/317678438/files/doc_presentations/2020/05/Investor-Call_ASGCT-2020_vF.pdf

Pfizer Announces Latest Results for DMD Gene Therapy, with Global Phase 3 Trial Expected to Begin Patient Dosing in the Second Half of the Year

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