SMA is caused by mutations in the SMN gene, which leads to the impairment of motor neurons, which work to control muscles and movement. Treatment with AVXS-101 delivers a functional copy of the SMN gene to motor neuron cells to enhance and restore motor neuron function. The gene copy is delivered by a harmless virus that can reach the brain by crossing the blood-brain barrier (a protective membrane that selects what enters the brain from the blood).
The Phase 1 study (NCT02122952) investigated the effects of AVXS-101 treatment by intravenous injection in 15 infants with SMA type 1 who were six months old or younger. Two doses were compared, the lower dose for Cohort 1 with three patients, and the higher dose for Cohort 2 with 12 patients.
The treatment’s short-term safety was evaluated over a two-year period, but a follow-up safety analysis will be carried out when the last patient reaches 2 years of age post-treatment. Patients will then be monitored annually as per standard of care for up to 15 years.
The endpoints measured were the time from birth to an “event” (death or at least 16 hours of daily ventilation support for 14 consecutive days in the absence of acute reversible illness or perioperatively) and the ability to sit independently, confirmed by video. Researchers also assessed patients with a standard motor milestone development survey and the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).
An interim data analysis, released lasted year, revealed a favorable safety profile with no new treatment-related safety or tolerability concerns identified. Motor skill improvements were also observed, especially in children treated with the higher dose.
As of Jan. 20, 2017, AVXS-101 maintains its safety profile and was well-tolerated by the patients. Indeed, 12 out of 12 patients (100%) who received the highest one-time therapeutic dose of AVXS-101 (Cohort 2) reached 13.6 months of age without events reported. Of note, the expected event-free survival rate for this disease is 25%.
Results also showed that 11 patients (92%) in this cohort achieved head control, nine patients (75%) were able to roll a minimum of 180 degrees from back to both left and right, and 11 patients (92%) could sit without help.
After the treatment, AveXis used three different measures to evaluate unassisted sitting with increasing amounts of time. Results showed that nine of 12 patients (75%) sat unassisted for five seconds, seven (58%) sat for at least 10 seconds, and five patients (42%) sat for 30 seconds or more. Also, two patients could walk independently, besides having achieved other milestones, including standing with support, standing alone, and walking with support.
In addition, as of Jan. 20, 2017, nine of nine patients (three in the low-dose cohort and six in Cohort 2) — reached 20 months without reported events. Here, the expected event-free rate is 8%.
“The completion of our Phase 1 clinical study of AVXS-101, the first ever gene therapy studied for the treatment of SMA type 1, is an exciting and eagerly awaited milestone, and we are quite pleased with these data,” Sean Nolan, AveXis’ president and CEO, said in a news release.
“The past few months have been productive for AveXis, and we look forward to continuing the momentum with several upcoming corporate catalysts … as well as ongoing collaborative discussions with regulatory authorities in the United States and Europe to explore the most expeditious pathways for marketing approval of AVXS-101,” Noland added.
The U.S. Food and Drug Administration (FDA) granted AVXS-101 Breakthrough Therapy and Fast Track designation for SMA type 1, and Orphan Drug status for all types of SMA.