BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
Dr. Jerry R. Mendell
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.