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LOS ANGELES -- A novel gene replacement therapy for the treatment of spinal muscular atrophy type 1 (SMA1) was both efficacious and well-tolerated, according to the small, phase III STRIVE study.

Treatment with AVXS-101 gene replacement therapy resulted in a meaningful increase in the CHOP-INTEND scores for SMA babies, reported John W. Day, MD, PhD, of Stanford University Medical Center in Stanford, California and colleagues, in a late-breaking emerging science poster.

A month after infusion, the participants experienced an average 7.8 point (range 3-13) improvement in CHOP-INTEND score, as well as a 17.3 point (range 12-23) improvement at 3 months.

These findings build upon a previous phase 1 trial of this therapy, which showed improved event-free survival time in SMA babies marked by 100% of patients (n=15) alive without need for permanent ventilation after 24 months. From an average score of 28.2 points at baseline, this improvement was marked by a 9.8 point score increase 1 month after treatment and an increase of 15.4 points at 3 months (P<0.001 for both) in the initial trial.

This trial had six participants, ages <6 months at the time of infusion, with 1 or 2 copies of the SMN2 gene with either bi-allelic SMN1 gene mutations or deletions. They were administered a intravenous dose of AVXS-101. The one-time dose works by delivering a copy of the SMN gene, packaged in a self-complementary, non-replicating scAAV9 (adeno-associated virus serotype 9). Because AAV9 can cross the blood-brain barrier, intravenous dosing is effective, the researchers noted.

Overall, the safety profile was favorable, with no serious adverse events reported in any patients. Although not clinically significant, there were two cases of patients experiencing transient elevations in transaminases >3x ULN, although both resolved with prednisolone treatment.

This abstract was one of several at the annual AAN meeting on novel treatment agents for SMA. Another study also reported favorable outcomes with an orally administered drug that showed a 6.5-fold increase in survival motor neuron protein levels after 4 weeks of treatment in SMA babies.

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