other novel treatments for two additional rare neurological monogenetic diseases, Rett syndrome and a genetic form of amyotrophic lateral sclerosis caused by mutations in the superoxide
dismutase 1 gene, or genetic ALS.
Pivotal Trial of AVXS-101 for the Treatment of SMA Type 1
In September 2017, based on the FDA's review of our clinical, non-clinical and chemistry, manufacturing and control, or CMC, data, including a
potency assay of AVXS-101, we initiated our pivotal trial of AVXS-101 for patients with SMA Type 1 using the intravenous, or IV,
formulation produced by our good manufacturing practice, or GMP, commercial manufacturing process. Three patients have been dosed in this clinical trial to date.
open-label, single-arm, single-dose, multi-center trial, which we call STR1VE, is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 of
1.1 × 1014 vg/kg, which is intended to be equivalent to the proposed therapeutic dose received by the second dosing cohort in our Phase 1 clinical trial
of AVXS-101 in patients with SMA Type 1.
trial will enroll a minimum of 15 patients with SMA Type 1 who are less than six months of age at the time of gene therapy, and who have one or two copies of the SMN2
backup gene as determined by genetic testing and bi-allelic SMN1 gene deletion or point mutations. There will be at least a four-week dosing interval between dosing of the first three patients to
allow review of the safety analysis from six time points (days one, two, seven, 14, 21 and 30), as well as early signals of efficacy, prior to dosing of the next patient.
intent-to-treat, or ITT, population is defined as patients who are less than six months of age and symptomatic at the time of gene therapy, with two copies of the SMN2 gene
as determined by genetic testing, bi-allelic SMN1 gene deletion and no c.859G>C mutation in SMN2. The intended enrollment will include at least 15 patients that meet the ITT criteria. The first three
patients will be ITT patients per the trial protocol definition and will be dosed four weeks apart to assess safety and efficacy using the Children's Hospital of Philadelphia Infant Test of
Neuromuscular Disorders, or CHOP INTEND.
co-primary efficacy outcome measures of the trial will include:
- The achievement of the developmental milestone of independent sitting for at least 30 seconds at 18 months of age; and
- Event-free survival at 14 months of age, with an event defined as either death or at least 16 hours per day of required
ventilation support for breathing for 14 consecutive days in the absence of acute reversible illness or perioperatively.
outcome measures will include:
- The ability to thrive, defined as the ability to remain independent from feeding support, tolerate thin liquids and maintain weight; and
- The ability to remain independent of ventilatory support at 18 months of age.
Phase 1 Clinical Trial of AVXS-101 for the Treatment of SMA Type 2
The open-label, dose-comparison, multi-center Phase 1 trial, which we call STRONG, is designed to evaluate the safety, optimal dosing
and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, utilizing a one-time IT route of administration. The trial will enroll 27 infants and
children who are symptomatic with a genetic diagnosis consistent with SMA, including the bi-allelic deletion of SMN1 and three copies of SMN2 without the SMN2