Pfizer Reports Failure in Persistent Pulmonary Hypertension, Progress in Duchenne Muscular Dystrophy

Pfizer logo on large outdoor sign

Roman Tiraspolsky /

Pfizer’s intravenous (IV) Revatio (sildenafil), when added to inhaled nitric oxide (iNO), failed to meet its primary efficacy endpoint in treating newborns with persistent pulmonary hypertension (PPHN).

Revatio is approved to treat adults with pulmonary arterial hypertension (PAH). PPHN is another type of high blood pressure which can be life-threatening. Prior to birth, a baby’s blood circulates differently in the uterus. With PPHN, the child does not shift over from fetal to normal newborn circulation, and blood is forced away from the lungs because of the high blood pressure in the arteries leading to the lungs. This decreases oxygen supply to the body.

The Phase III clinical trial had two consecutive parts. The first, Part A, was a randomized, placebo-controlled, double-blind interventional phase. It assessed the efficacy and safety of the therapy. The results reported today are based on Part A.

Part B is the non-interventional phase with follow-up at 12 and 24 months after the end of the trial to evaluate developmental progress. Part B is ongoing.

The trial did not result in a statistically significant decrease in treatment failure rate or time on iNO compared to treatment with iNO alone.

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Pfizer also reported initial Phase Ib clinical data on PF-06939926, a gene therapy for Duchenne muscular dystrophy (DMD). They presented the data at the 25th Annual Parent Project Muscular Dystrophy (PPMD) Connect Conference held in Orlando, Florida.

The primary endpoint of the Phase Ib trial is safety and tolerability of the therapy. Secondary endpoints measured expression of mini-dystrophin distribution within muscle fibers.

DMD is a genetic disease marked by progressive muscle degeneration and weakness. It primarily affects boys. Boys with the disease often die in their 20s, although there are now treatments, primarily Sarepta Therapeutics’ controversial Exondys 51, which was approved by the U.S. Food and Drug Administration (FDA) in 2016.

The disease is the result of an absence of dystrophin, a protein that helps keep muscle cells intact. One of the difficulties in developing gene therapies for DMD is the size of the dystrophin gene, the largest in the human genome. It is too large to be inserted into cells using traditional viral vectors. As a result, most approaches for gene therapy use gene-skipping technology or truncated versions of the dystrophin gene that produce partial but still functional dystrophin proteins.

Pfizer’s gene therapy uses recombinant adeno-associated virus serotype 9 (AAV9s ) to carry a shortened version of the human dystrophin gene under the control of a human muscle-specific promoter.

The preliminary data showed the most common adverse events were nausea, vomiting, decreased appetite, tiredness and/or fever. Preliminary efficacy data included muscle biopsies of the biceps taken two months after dosing in a small subgroup of the trial. It showed detectable mini-dystrophin immunofluorescence signals with a mean of 38% positive fibers at one dose and 69% at a higher dose.

“Gene therapy for single-gene disorders is at a formative stage in tis evolution, and the initial data we’ve seen in our study for Duchenne muscular dystrophy may exemplify the potential for this modality to change patients’ lives,” stated Seng Cheng, senior vice president and chief scientific officer of Pfizer’s Rare Disease Research Unit. “We are looking forward to building on these initial data and advancing the development of this therapeutic modality.”

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