SEC Filings

10-Q
AVEXIS, INC. filed this Form 10-Q on 11/09/2017
Entire Document
 

 

The 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 x 1014 vg/kg, which is equivalent to the proposed therapeutic dose received by the second dosing cohort in our Phase 1 trial, in patients with SMA Type 1.

 

The 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.

 

The 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 3 patients will be ITT patients per the trial protocol definition and will be dosed 4 weeks apart to assess safety and efficacy using CHOP INTEND.

 

The co-primary efficacy outcome measures of the trial will include:

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The achievement of the developmental milestone of independent sitting for at least 30 seconds at 18 months of age; and

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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.

 

Co-secondary outcome measures will include:

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The ability to thrive, defined as the ability to remain independent from feeding support, tolerate thin liquids and maintain weight; and

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The ability to remain independent of ventilatory support at 18 months of age.

 

Top-Line Results of Phase 1 Clinical Trial 

 

In our fully enrolled Phase 1 clinical trial, we treated 15 SMA Type 1 patients, divided into two dosing cohorts, and observed a favorable safety profile and that AVXS-101 is generally well-tolerated. As of August 7, 2017, all patients in the study have survived event free, in contrast to the 8% event free rate demonstrated in an independent, peer-reviewed natural history study for patients with SMA Type 1. Additionally, we have observed improved motor function, including in some patients, the attainment of motor milestones such as the ability to sit unassisted, crawl, stand and walk — motor milestone achievements that are essentially never seen among untreated patients suffering from SMA Type 1. The open-label, dose-escalating study was designed to evaluate the safety and tolerability of AVXS-101 in patients with SMA Type 1. The key measures of efficacy were the time from birth to an "event," which was 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, and video confirmed achievement of ability to sit unassisted. Additionally, several exploratory objective measures were assessed, including a standard motor milestone development survey and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, or CHOP INTEND.

 

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Event-free Survival and Safety:  Data as of August 7, 2017, showed no new events, and 15 of 15 patients (100%) were event-free at 20 months of age. The expected event-free survival rate at 20 months based on the natural history of the disease is 8%. Based on data accumulated up to this date, AVXS-101 appeared to have a favorable safety profile and to be generally well tolerated, with no new treatment related safety or tolerability concerns identified. The median age at last follow-up was 25.7 months and 30.8 months for patients who received a dose of AVXS-101 administered in the proposed therapeutic dose-cohort and in low-dose cohort, respectively. Use of the term "proposed therapeutic dose" does not imply that we have established efficacy, but this one-time dose is the dosing level that we presently intend to evaluate in future trials.

 

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