Pfizer puts Bamboo’s muscular dystrophy gene therapy to the test

Pfizer's mini-dystrophin therapy aims to prevent muscle function loss in DMD. (maria-anne/Pixabay)

Pfizer has dosed the first patient in a trial of a Duchenne muscular dystrophy (DMD) gene therapy acquired as part of its $700 million takeover of Bamboo Therapeutics in 2016.

The phase 1b trial got underway at Duke University Medical Center last month, when a boy with DMD received a single infusion of mini-dystrophin candidate PF-06939926, one of the key assets behind the acquisition. The target enrollment in the trial is 12 patients, and Pfizer is hoping to have the first results available in the first half of next year.

PF-06939926 is an adeno-associated virus (AAV) capsid containing a gene for a shortened version of human dystrophin, a protein that helps keep muscle cells intact, as well as a promoter sequence. The dystrophin gene is too large to fit onto an AAV vector, so gene therapy developers are using truncated versions that they hope will still be able to correct the defect.


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The trial will be a key test of Bamboo’s recombinant AAV vector design and production platform, a key part of Pfizer’s broad push into gene therapy alongside its collaborations with Spark Therapeutics and Sangamo.

Pfizer is hoping the gene therapy will be an effective one-shot treatment for DMD, providing patients with a functional copy of dystrophin that will stop or delay the progressive muscle deterioration and weakness that characterizes the disease.

Sarepta’s exon-skipping therapy Exondys 51 (eteplirsen) was the first drug to be approved by the FDA for the disorder, and remains the only treatment to address the underlying defect in DMD. However, it is suitable for use only in a subset of patients with a specific dystrophin mutation and there has been debate about its efficacy. Another mutation-targeting drug—PTC Therapeutics’ Translarna (ataluren)—was turned down by the FDA in October but has been approved in Europe.Meanwhile, Sarepta has a follow-up to Exondys 51 in development.

“We’ve listened to the patient community and we know there is a dire need for treatment options,” commented Greg LaRosa, Ph.D., chief scientific officer of Pfizer’s rare disease research unit. “With this in mind, we have built on important scientific advances to design a therapy with the potential to deliver the mini-dystrophin gene to the body and address the underlying cause of DMD, regardless of mutation.”

At least two other trials of DMD gene therapies are also ongoing in the U.S., both involving candidates developed at Nationwide Children’s Hospital (NCH) and partnered by Sarepta. One of the two phase 1/2 trials is based on delivery of a 'microdystrophin' gene sequence while the other is focused on the GALGT2 gene. Animal studies suggest over-expression of GALGT2 can result in normal muscle function even in the absence of dystrophin. Last month, a phase 1/2 trial of Solid Biosciences' microdystrophin candidate SGT-001 was placed on clinical hold after a patient was hospitalized.

The start of Pfizer’s trial was welcomed by the Cure Duchenne charity’s founder and CEO Debra Miller, who said, “the momentum we are seeing in the field of gene therapy emphasizes the maturing opportunity to advance the science.”

We applaud the important step Pfizer has taken to advance a potentially transformational treatment option for boys stricken with this terrible disease,” she added.

Pfizer’s most advanced gene therapies are Sangamo’s PF-07055480 (formerly SB-525) and Spark’s PF-06838435, which are in phase 2 testing for hemophilia A and B, respectively.

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