Clinical Trials

Date: 2018-01-16

Type of information: Initiation of the trial

phase: 3

Announcement: initiation of the trial

Company: Avexis (USA - IL)

Product: AVXS-101 (adeno-associated virus serotype 9 expressing the human Survival Motor Neuron gene)

Action mechanism:

gene therapy. AVXS-101 is a proprietary gene therapy candidate of a one-time treatment for SMA Type 1 and is the only clinical-stage gene therapy in development for SMA. AVXS-101 is designed to address the monogenetic root cause of SMA and prevent further muscle degeneration by addressing the defective and/or loss of the primary SMN gene. AVXS-101 also targets motor neurons providing rapid onset of effect, and crosses the blood brain barrier allowing an IV dosing route and effective targeting of both central and systemic features.
AVXS-101 - ChariSMA™ is a recombinant AAV9 in which most of the AAV9’s naturally-occurring components have been removed and replaced with the SMN transgene and other elements such as the CB promoter and the Bovine Growth Hormone polyadenylation signal (BGH pA) added for hydrolytic enzymatic protection and mRNA stability. The viral vector will deliver the SMN transgene into the motor neurons. Protein synthesis from the SMN transgene will produce full-length, functional SMN protein.

Disease: spinal muscular atrophy (SMA) Type 1

Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases

Country: Belgium, France, Germany, Italy, The Netherlands, Spain, Sweden, UK

Trial details:

The Phase 3, open-label, single-arm, single-dose, trial of AVXS-101 (gene replacement therapy) in patients with spinal muscular atrophy (SMA) Type 1 who meet enrollment criteria and are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). Up to 30 patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled. (NCT03461289)

Latest news:

• On January 16, 2018, AveXis provided an overview of the expanded clinical development program for AVXS-101, for the treatment of spinal muscular atrophy (SMA). In addition to the ongoing pivotal trial in SMA Type 1 (STR1VE) and the ongoing Phase 1 trial in SMA Type 2 (STRONG), the company plans to initiate three studies to further evaluate AVXS-101, including in new SMA patient populations.
A pivotal trial of AVXS-101 in SMA Type 1 is planned in Europe (STR1VE EU): The trial is expected to reflect a single-arm design, using natural history of the disease as a comparator, and is expected to enroll approximately 30 patients with SMA Type 1 who are less than six months of age at the time of gene therapy. The trial is designed to evaluate safety and efficacy of a one-time IV dose of AVXS-101, including achievement of motor milestones, specifically patients’ ability to sit unassisted, as well as an efficacy measure defined by the time from birth to an “event,” defined as death or requiring at least 16 hours per day of ventilation support for breathing for greater than two weeks in the absence of an acute reversible illness, or perioperatively. AveXis incorporated scientific advice from the European Medicines Agency into the protocol design, and expects to initiate the trial in the first half of 2018.