Data presented at a medical conference last Friday provided a peek at the potential efficacy of a gene therapy under development by Pfizer for a rare genetic disorder that causes muscle degeneration.
The New York-based drugmaker on presented preliminary data from six boys taking part in its Phase Ib study of PF-06939926 at the Parent Project Muscular Dystrophy Connect Conference in Orlando. The therapy is an adeno-associated viral vector-based gene therapy for Duchenne muscular dystrophy. DMD, which manifests in early childhood and ultimately causes premature death, is the most common form of muscular dystrophy, occurring in 1 out of every 3,500 to 5,000 male births.
In addition to assessing the safety and tolerability of the gene therapy, the study also looked at a secondary efficacy endpoint of mini-dystrophin distribution within muscle fibers. Dystrophin is a protein that is mainly concentrated in the muscle tissue and is used for movement, including in the heart. DMD, however, causes an absence of dystrophin, leading to progressive muscle weakness.
Pfizer noted that there is currently no industry standard for defining a normal range of dystrophin concentration, which can vary widely. However, the company used an internal test to measure levels in the six boys who received the gene therapy at doses of either 100 trillion or 300 trillion vector genomes per kilogram of body weight.
Based on open-muscle biopsies taken two months after dosing, patients who received the 100 trillion-vector dose showed detectable mini-dystrophin in a mean of 38 percent of muscle fibers, while the figure was 69 percent among patients receiving the 300 trillion-vector dose. Mini-dystrophin concentrations ranged from 10-60 percent of “normal” for all study participants, including 23.6 percent for the 100 trillion-vector cohort and 29.5 percent for the 300 trillion-vector cohort. Two patients receiving the lower dose, who had 12 months of follow-up, showed improvements in a test of ambulatory function. Common adverse events suspected to be related to the gene therapy include nausea, vomiting, decreased appetite, tiredness and fever, with one patient having to be hospitalized for two days due to nausea and vomiting.
The bigger question concerning the data is where it places Pfizer in the competitive landscape around DMD, particularly with respect to Sarepta Therapeutics, which is developing its own gene therapy for the disease. And it would appear investors thought Sarepta came out looking better. Following the release of the Pfizer data Friday, the Cambridge, Massachusetts-based company’s shares surged 14 percent on the Nasdaq.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
On the one hand, Cowen analyst Ritu Baral wrote in a note to investors Monday, PF-06939926 may ultimately qualify for Food and Drug Administration approval. However, while the Pfizer construct’s efficacy is likely inferior or equal to Sarepta’s, the data raise questions about the former’s safety at high doses. Baral wrote that the data suggest Pfizer’s construct is both less potent and less safe than Sarepta’s, for which Phase II data are expected in mid-2020. While Pfizer said it plans to start a placebo-controlled trial of the therapy in the first half of next year, Baral wrote that it is highly unlikely, and the drugmaker has more dose-finding and chemistry, manufacturing and control optimization work to complete.
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