The study, called STRONG, will begin immediately, AveXis said.
“We are quite pleased to initiate our first trial of AVXS-101 in patients with SMA Type 2,” Sean Nolan, the company’s president and CEO, said in a press release.
“Our goal has been to expand the study of gene therapy beyond Type 1 infants to address the urgent medical needs of children with SMA Type 2, and we look forward to understanding the potential clinical impact of AVXS-101 in these patients who, left untreated, will never walk on their own and most will never stand without assistance,” Nolan said.
The study will include 27 patients in two age groups — those younger than 2 years old and those aged 2 to 5. All patients will have genetically confirmed SMA with three copies of the SMN2 backup gene. To be considered for the trial, they have to be able to sit, but have never walked independently.
Researchers will assess two doses of the treatment. To make study processes as safe as possible, researchers will wait for at least four weeks in between the dosing of the first three patients for each dose.
Three patients in the younger group first will be treated with the lower dose of the gene therapy. If considered safe, researchers will test a higher dose in three more patients, aged 2 to 5. The study then will proceed to enroll 21 more patients — 12 for each age group — who will receive the higher dose of the treatment.
Outcome measures will differ in the two patient groups. For children younger than two years, the primary outcome will be the ability to stand without support. Secondary measures will include walking and developmental abilities
“This Phase 1 trial in children with SMA Type 2 will allow us to evaluate safety, optimal dosing, and proof-of-concept for efficacy of AVXS-101 compared to the well-characterized natural history using the one-time intrathecal [into the spinal column] route of administration,” said Sukumar Nagendran, MD, chief medical officer of AveXis.
“Because AVXS-101 targets the root cause of SMA, we are optimistic that we will observe a similar preclinical to clinical translation in this Type 2 trial as was seen in the SMA Type 1 study using intravenous administration.”
The company’s Phase 1 study in Type 1 SMA infants showed impressive results in most infants, many of whom obtained head control and sit unassisted. In May 2017, two of the treated infants could crawl or walk independently — a stark contrast to the outcomes seen in untreated SMA Type 1 babies. Most of these infants are dead by 18 months.
AveXis has now started enrolling Type 1 SMA infants into a Phase 3 trial (NCT03306277) of AVXS-101.