AveXis Announces Expanded Clinical Development Program for AVXS-101 in Spinal Muscular Atrophy

By Cure SMA | Published On April 25, 2018

AveXis Announces Expanded Clinical Development Program for AVXS-101 in Spinal Muscular Atrophy

AveXis, a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today provided an overview of the expanded clinical development program for the company’s initial gene therapy candidate, 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. Additionally, the company announced the first patient has been dosed in the Phase 1 trial of AVXS-101 in SMA Type 2.

“Our focus has always been to serve the SMA community, and our expanded clinical development program is designed to evaluate the impact of AVXS-101 in a broader set of SMA patients,” said Dr. Sukumar Nagendran, Chief Medical Officer of AveXis. “We believe the year ahead has the potential to be one of significant clinical progress as we continue toward our ultimate goal of bringing AVXS-101 to the patients and families devastated by SMA.”

Clinical Development Program Overview of AVXS-101 for the Treatment of SMA

Ongoing Clinical Trials

  • Pivotal Trial of AVXS-101 in SMA Type 1 (STR1VE): The ongoing, open-label, single-arm, single-dose, multi-center trial is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 in patients with SMA Type 1. The trial is expected to 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. Three patients have been dosed to date.
  • Phase 1 Trial of AVXS-101 in SMA Type 2 (STRONG): The on-going, open-label, dose-comparison, multi-center Phase 1 trial 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 intrathecal (IT) route of administration. The trial is expected to 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 genetic modifier, who are able to sit but have no historical or current ability to stand or walk. One patient has been dosed to date.

Planned Trials in SMA

  • Pivotal Trial of AVXS-101 in SMA Type 1 in Europe (STR1VE EU): The planned 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. 
  • Pre-Symptomatic SMA Types 1, 2, 3 (SPRINT): The planned multi-national trial is expected to enroll approximately 44 patients with two, three and four copies of SMN2 who are less than six weeks of age and pre-symptomatic at the time of gene therapy. The trial is designed to evaluate appropriate clinical endpoints, including developmental milestones, survival, bulbar function and safety, of a one-time IV infusion of AVXS-101. AveXis expects to initiate the trial in the first half of 2018, and will provide more design details at the time of initiation.
  • Pediatric “All Comers” with SMA Types 1, 2, 3 (REACH): The planned multi-national trial is expected to enroll approximately 50 patients between approximately six months and 18 years of age who do not qualify for other AVXS-101 trials at the time of gene therapy. The trial is designed to evaluate a one-time IT dose of AVXS-101. AveXis expects to initiate the trial in late Q4 2018 or early 2019, and will provide more trial design details at the time of initiation.

Cure SMA Funds Multiple Gene Therapy Approaches

Beginning in 2010, Cure SMA made a series of grants to Nationwide Children’s Hospital (NCH) to study gene therapy, also called gene transfer. Spinal muscular atrophy (SMA) is caused by a mutation in the survival motor neuron 1 gene (SMN1). Because of this mutation, the individual does not produce enough survival motor neuron (SMN) protein.

Gene transfer may increase SMN levels by using a virus, called a vector, to deliver the SMN1 gene to affected cells. Researchers at NCH discovered that Adeno-associated virus serotype 9 (AAV9) had the unique ability to cross the blood brain barrier and the Blood-Cerebrospinal Fluid Barrier (CSF).

Currently, two approaches are being studied: an injection into a vein, known as systemic delivery, and delivery directly into the cerebrospinal spinal fluid (CSF), a process known as CSF-delivered gene therapy. CSF-delivered gene therapy has shown promise for reducing the amount of drug required for larger and older patients. This could eventually make the treatment accessible to a wider population.

In total, Cure SMA has granted $845,000 for gene therapy, including support for both the systemic program and the CSF program. Using the data generated with our funding for CSF delivery, researchers were able to secure a $4 million grant from NINDS in 2013, to develop this delivery approach for human clinical trials in SMA.

Topics: Clinical Trials, Research

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