Novartis announced Friday that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended conditional marketing approval of Zolgensma (onasemnogene abeparvovec) for the treatment of spinal muscular atrophy (SMA). Dave Lennon, president of Novartis' AveXis unit, said the positive opinion "marks a critical step closer to…bringing the only gene therapy for SMA to Europe."
Specifically, the one-time administered gene therapy is being recommended for use in 5q SMA patients with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA Type 1, or for 5q SMA patients harbouring a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene.
The CHMP's positive opinion was backed by data from the Phase III STR1VE-US and Phase I START trials, which evaluated a one-time intravenous infusion of Zolgensma in symptomatic SMA Type 1 patients less than six 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. Novartis recently reported that in STR1VE-US, 91% of patients met the co-primary endpoint of event-free survival at 14 months, while 59% of participants met the other main goal of sitting for at least 30 seconds at 18 months of age, "a milestone never achieved in the natural history of SMA Type 1." The comparable Phase III STR1VE-EU study is ongoing.
The filing also includes interim data from the ongoing Phase III SPR1NT trial, assessing a single, one-time intravenous infusion of Zolgensma in presymptomatic patients less than six weeks of age at dosing who are 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," the company said.
Zolgensma was approved in the US in May 2019 for SMA patients under two with bi-allelic mutations in the SMN1 gene, with Novartis setting a price of around $2.1 million for a single intravenous infusion. The adeno-associated virus vector-based gene therapy, which generated sales of $186 million in last year's fourth quarter, was also cleared earlier this month by regulators in Japan.
Lennon indicated that Novartis would be offering governments and reimbursement bodies a so-called "Day One" programme to make Zolgensma rapidly available, should it eventually be approved in Europe. The access scheme "is designed to ensure that the cost of patients treated before national pricing and reimbursement agreements are in place, are aligned with the value-based prices negotiated following clinical and economic assessments," the company explained. Some options that can be customised for countries include retroactive rebates to make sure early access costs are aligned with negotiated prices, deferred payments and installments, and outcomes-based rebates. Novartis noted that it is already in advanced talks with several countries in Europe to agree on terms of the programme.
Roche recently announced positive results from the SUNFISH and FIREFISH studies of its experimental SMN2 splicing modifier risdiplam in certain patients with SMA. It also recently initiated a global pre-approval access/compassionate-use programme for the therapy. The FDA is currently assessing risdiplam under a priority review, with a decision scheduled by May 24. For related analysis, see KOL Views Results: Leading neurologist sees risdiplam as a real problem for Spinraza in SMA.
Meanwhile, Biogen and Ionis Pharmaceuticals' SMA treatment Spinraza (nusinersen), which requires infusion into the spinal canal every four months, was cleared in the US in 2016, with EU approval granted the following year.
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