Pfizer Announces First-in-Human Early Data for PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy

On the 29th, Pfizer Inc. announced preliminary results from its Phase 1b clinical trial of PF-06939926, a gene therapy designed to treat Duchenne muscular dystrophy (DMD). The trial results demonstrated that this gene therapy increased dystrophin expression levels in patients' muscles and improved functional muscle metrics.

Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration and weakness, with symptoms typically emerging between the ages of 3 and 5. Patients usually lose the ability to walk during their teenage years, and as the disease affects cardiac and respiratory muscles, it ultimately leads to premature death. DMD is the most common form of muscular dystrophy worldwide, affecting approximately 1 in every 3,500 to 5,000 male births. Currently, there is no curative treatment for this condition. Since DMD is caused by mutations in the gene encoding dystrophin, gene therapy is considered a promising potential cure.

PF-06939926, developed by Pfizer, is an investigational gene therapy. It consists of a “mini-dystrophin” transgene controlled by a human muscle-specific promoter, packaged in an adeno-associated virus serotype 9 (AAV9) vector. The AAV9 viral vector has the ability 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 clinical trial, six patients aged 6–12 years received a single dose of PF-06939926 at either 1E14 vg/kg (low dose) or 3E14 vg/kg (high dose). The primary endpoints were safety and tolerability, while secondary and exploratory endpoints included the expression level of mini-dystrophin in muscle fibers and other measures of muscle function.

Image source: Pfizer's official website

Preliminary trial results indicated that, after 2 months of treatment, the proportion of muscle fibers expressing mini-dystrophin in biceps brachii samples was 38% in patients receiving low-dose therapy and 69% in those receiving high-dose therapy.

Using the mass spectrometry assay developed by Pfizer, the expression level of micro-dystrophin in muscle tissue was 23.6% of normal levels in the low-dose group and 29.5% in the high-dose group.

Additionally, Pfizer conducted muscle function assessments in two patients receiving low-dose therapy. After one year of treatment, both patients showed a 4.5-point improvement in their North Star Ambulatory Assessment (NSAA) scores, from baseline values of 24 and 25, respectively. Typically, NSAA scores in Duchenne muscular dystrophy (DMD) patients of this age group remain stable or decline with age.

“The therapeutic model of using gene therapy to treat monogenic diseases is gradually taking shape. Preliminary data from studies in patients with Duchenne muscular dystrophy (DMD) indicate that this approach has the potential to transform patients’ lives,” said Dr. Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizer’s Rare Disease Research Unit. “We look forward to further advancing the development of this therapeutic model based on these early data.”

Pfizer will continue to collect data from this open-label study and plans to initiate a randomized, placebo-controlled, global Phase 3 clinical trial. This Phase 3 trial is expected to launch in the first half of 2020.

Original Title:Flash | Gene Therapy for DMD: Pfizer Releases Early Human Trial Data for the First Time, Plans to Initiate Phase 3 Clinical Trials

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