Data from a trial of Pfizer’s gene therapy for Duchenne muscular dystrophy (DMD) have shown signs of efficacy, but also safety concerns that sparked an uptick in shares for rival developers.
The data came from six of a planned population of 12 patients aged 5 to 12 in the phase 1b study of PF-06939926, and produced the headline news of a serious immune reaction in one child on the trial.
This involved an acute kidney injury, haemolysis, and reduced platelet count and required hospitalisation in intensive care, dialysis and treatment with Alexion’s kidney drug Soliris (eculizumab).
Other side effects including nausea, vomiting and fever were seen in four of the six patients. In three of the children, nausea/vomiting could be controlled with oral anti-emetic drugs, but in one case the side effects were so bad the patient had to be hospitalised for two days.
There were signs of efficacy, with the gene therapy achieving expression levels of ‘mini-dystrophin’ – a truncated form of the protein that is deficient in DMD – in the 10% to 60% of normal range, depending on the dose administered.
Two patients had at least one year of follow-up and showed modest increases in the NorthStar Ambulatory Assessment (NSAA) scale, used to assess symptoms caused by the muscle-wasting disease. Typically children with DMD would have stable NSAA scores or see a slight decline over that timeframe.
Pfizer is vying with Sarepta and Solid Biosciences to bring a gene therapy for DMD through development, and inevitably the side-effect issue buoyed its rivals, even though all the patients in the phase 1b trial made a full recovery.
Shares in Sarepta – which already markets a drug to treat DMD and reported encouraging results with its AAVrh74.MHCK7 candidate last year – closed up 17% ahead of the weekend and made additional gains after hours.
Solid Bio meanwhile gained almost 14%, despite posting what were seen as disappointing dystrophin expression levels in a phase 1/2 trial of its SGT-001 DMD gene therapy candidate earlier this year.
Pfizer adopted a cautious tone in its assessment of the data, with Seng Chen, chief scientific officer for the company’s rare disease unit, saying the results “may exemplify the potential for this modality to change patients’ lives.”
The company is however pressing ahead with plans for a pivotal trial of PF-06939926, currently expected to get underway in the first half of 2020.
According to Reuters, both the hospitalisations occurred in patients on the highest dose of the gene therapy, which also produced the most robust improvements in dystrophin expression.
Pfizer has said it will test the higher dose in its upcoming phase 3 trial, possibly alongside an intermediate dose, and will include strategies to reduce the risk of side effects.