Novartis’s AveXis unit has received a CHMP nod for the spinal muscular atrophy gene therapy at its latest meeting, sending it on the final steps to market in the EU.

After several delays plus a row over a controversial lottery-style managed access program in Europe, Novartis gene therapy Zolgensma (onasemnogene abeparvovec) has finally been granted a positive opinion by the EU’s Committee for Medicinal Products for Human Use (CHMP).

The committee has recommended a conditional marketing authorization of Zolgensma 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.

Image: iStock/artJazz

To speed the product to patients, the Novartis gene therapy unit AveXis said it would offer an “innovative ‘day one’ access program” to EU governments and reimbursement agencies to enable immediate access at time of EMA approval, expected by June 2020.

Pricing negotiations for the potentially one-time therapy will now be key. The company estimates that in Europe, the cumulative estimated healthcare costs per child with SMA ranges between €2.5 to €4m within the first 10 years.

Zolgensma was launched in its first market, the US, in June last year with a $2.1m price tag, and got off to an impressive start. Novartis noted that full-year sales were $361m, with $186m coming in the fourth quarter when 100 new patients were treated.

At its fourth quarter results presentation, CEO Vas Narasimhan said the launch continued to progress well, and noted that reimbursement policies were in place covering 97% of commercial patients and over 50% of Medicaid patients.

New five-year data are also strengthening arguments that the gene therapy’s effects are long-lasting and that the product truly does provide a one-time treatment.

Zolgensma is expected to become the standard of care for newborn-screened and young type 2 SMA patients. It has also just been approved in Japan for the treatment of SMA in patients under the age of two, including those who are pre-symptomatic at diagnosis. Here, too, all eyes are on pricing.

The route to EU approval has been slower than Novartis would have wanted. Last September, the company was given more time to respond to outstanding issues the CHMP had adopted in June regarding the marketing authorization application (MAA). At the time, Zolgensma was at the heart of a data manipulation controversy in the US. A second list of outstanding issues was adopted in December, according to the agenda for the March CHMP meeting.

Previously, it had emerged that the MAA for Zolgensma had lost the accelerated assessment it had been granted originally and had reverted to the standard review timeline. Zolgensma had been receiving support under PRIME, the EMA’s priority medicines scheme, where products are expected to get accelerated assessment.

AveXis president Dave Lennon told Scrip the outstanding issues that the CHMP had in September were around manufacturing, since the product used in its Phase I trial was made academically and was not the commercial grade product being used in the Phase III trials. “Most of the questions are around are they bioequivalent, and/or can you show that they’re clinically equivalent to your clinical trials,” he said.

Meanwhile, the company has had to deal with a backlash against lottery-style managed access program for the product outside the US.

This article was first published on 27 March 2020 in Scrip.

Alex Shimmings has more than 20 years’ experience covering pharmaceutical and biotech R&D and can be reached at [email protected] or @ScripAlexS