FDA Approves AveXis’ Pivotal Trial of AVXS-101 for SMA Type 1

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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The gene therapy developer AveXis will start a pivotal clinical trial of AVXS-101 for people with spinal muscular atrophy (SMA) type 1.

U.S. Food and Drug Administration officials agreed to the trial after AveXis submitted information the agency requested on the drug’s manufacturing process and other matters. The request was made at a meeting the sides held in May.

AveXis did not say in its announcement whether the pivotal trial would be a Phase 2 or Phase 3 study. The company has completed a Phase 1 trial of AVXS-101. Most pivotal trials are Phase 3, but occasionally they can be Phase 2.

“We are pleased to reach this outcome following a thorough review by the FDA of the voluminous information we supplied to address the [manufacturing] commitments made during the Chemistry, Manufacturing, and Controls Type B meeting in May,” Sean Nolan, the president and CEO of AveXis, said in a press release. The company is “eager to initiate our pivotal trial of AVXS-101 in SMA Type 1 in the U.S.” with a treatment produced in its certified manufacturing process, he said.

“Moving AVXS-101 back into the clinic, as planned, with product from our GMP [certified manufacturing] process is a significant milestone, not only for AveXis but also for the patients we hope to serve,” he said.

AVXS-101 is a proprietary gene therapy for SMA types 1 and 2. Designed to deliver a functional copy of an SMN gene to motor neuron cells, it aims to prevent additional muscle degeneration.

The pivotal trial in SMA type 1 – called STR1VE – will be an open-label, single-arm, single-dose, multi-center study. It will evaluate the safety and effectiveness of a one-time dose of AVXS-101 delivered intravenously or directly into the blood circulation.

Researchers will administer a dose established in a Phase 1 trial that they confirmed with new analytical methods that the FDA reviewed. The dose was also extensively tested in a mouse model of SMA.

AveXis expects to enroll in the trial at least 15 patients with SMA Type 1 younger than six months of age. Patients will have genetic tests to confirm that they carry one or two copies of the SMN2 gene, that they have no c.859G>C gene mutation, and that they have no SMN1 gene deletion or point mutations in both alleles. An allele is an alternative form of a gene. People typically have two alleles for a single trait, one inherited from each parent.

After administering AVXS-101 to the first three patients, researchers will wait at least four weeks to evaluate the treatment’s safety and look for early signs of effectiveness before dosing the next group.

One of the trial’s primary objectives will be to see if AVXS-101 can help an 18-month-old infant sit without help for at least 30 seconds. Another primary objective will be to help an infant achieve event-free survival at 14 months of age. Researchers define an event as either death or at least 16 hours a day of ventilation support for breathing for 14 consecutive days.

A secondary objective of the trial will be to see whether AVXS-101 helps patients thrive — that is,  not requiring feeding support, tolerate thin liquids and maintain weight. Another secondary objective will be to help infants get off ventilator support at 18 months of age.

The trial will be conduced at 16 centers in the United States: Lurie Children’s Hospital of Chicago; Boston Children’s Hospital; Children’s Hospital Colorado; Children’s Hospital of Philadelphia; Columbia University; David Geffen School of Medicine at UCLA; Duke University; Johns Hopkins Pediatric Neurology; Nationwide Children’s Hospital; Oregon Health and Science University; Stanford University Medical Center; University of Central Florida College of Medicine; University of Texas Southwestern Medical Center; University of Utah; University of Wisconsin; and Washington University School of Medicine.

“We are appreciative of the detailed reviews and timely feedback we have received from the FDA,” said James L’Italien, AveXis’ chief regulatory and quality officer. “We look forward to our end-of-Phase 1 meeting, which has been scheduled for late in the fourth quarter, to discuss next steps in the regulatory process for AVXS-101.”

AveXis and the FDA are continuing their conversation. It includes how much AVXS-101 should be administered to the intrathecal space that holds cerebrospinal fluid during a clinical trial planned for patients with SMA Type 2. Updates of these studies are expected at the end of the year.