AveXis/Novartis receives EC approval and activates “Day One” access program for Zolgensma, the only gene therapy for spinal muscular atrophy (SMA).

AveXis, a Novartis company, announced the European Commission (EC) granted conditional approval for Zolgensma (onasemnogene abeparvovec) for the treatment of patients with 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA Type 1; or for patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene. The approval covers babies and young children with SMA up to 21 kg according to the approved dosing guidance. In Europe each year, approximately 550–600 infants are born with SMA, a rare, genetic neuromuscular disease caused by a lack of a functional SMN1 gene, resulting in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement. Zolgensma is a one-time gene therapy designed to address the genetic root cause of the disease by replacing the function of the missing or nonworking SMN1 gene. Administered during a single, intravenous (IV) infusion, Zolgensma delivers a new working copy of the SMN1 gene into a patient’s cells, halting disease progression. According to Pediatric Neuromuscular Clinical Research (PNCR) natural history study of SMA, almost all patients under the age of five years of age will be under 21kg with some patients at 6, 7 or 8 weighing below 21 kg. AveXis is planning a product presentation that allows for treatment of patients weighing up to 21 kg and is working with the European Medicines Agency (EMA) to finalize supply timelines. SMA is a significant burden to the healthcare system in Europe with cumulative estimated healthcare costs per child ranging between €2.5 to €4 million within the first 10 years alone. Zolgensma is a transformative and highly innovative one-time gene therapy for a devastating and progressive genetic disease and is consistently priced worldwide under a value-based framework, however final pricing and reimbursement decisions are determined at the local level. Designed to work within existing, local pricing and reimbursement frameworks, the “Day One” access program offers ministries of health and reimbursement bodies a variety of flexible options that can be implemented immediately to support swift access and broad reimbursement. The “Day One” access program ensures the cost of patients treated before national pricing and reimbursement agreements are in place align with the value-based prices negotiated following clinical and economic assessments. The program maintains the integrity of the local pricing and reimbursement frameworks with a variety of customizable options including:• Retroactive rebates ensuring early access costs are aligned with negotiated prices following local clinical and economic assessment processes.• Deferred payments and installment options allowing reimbursement bodies to manage budget impact during the early access phase.• Outcomes-based rebates negotiated following clinical and economic assessments can be applied to patients treated during the early access period.• Robust training for treating institutions on administration and follow-up care.• Access to RESTORE, a global registry of patients who have been diagnosed with SMA that draws upon existing country registries. Immediate access to Zolgensma, aligned to the label, is available in France through the ATU framework and expected shortly in Germany. The EC approval is based on the completed Phase III STR1VE-US and Phase 1 START trials that evaluated the efficacy and safety of a one-time IV infusion of Zolgensma in symptomatic SMA Type 1 patients <6 months of age at dosing, who had one or two copies of the smn2 backup gene, or two copies of the smn2 backup gene, respectively. str1ve-eu, a comparable phase iii study is ongoing. zolgensma demonstrated prolonged event-free survival; rapid motor function improvement, often within one month of dosing; and, sustained milestone achievement, including the ability to sit without support, crawl and walk independently – milestones never achieved in untreated type 1 patients. additional supportive data included interim results from the ongoing spr1nt trial, a phase iii, open-label, single-arm study of a single, one-time iv infusion of zolgensma in pre-symptomatic patients (><6 weeks at age of dosing) genetically defined by bi-allelic deletion of smn1 with 2 or 3 copies of smn2. these data demonstrate rapid, age appropriate major milestone gain, reinforcing the critical importance of early intervention in sma patients. .>