Novartis back with bid for 'multibillion-dollar' Zolgensma expansion in older SMA patients as FDA lifts clinical hold

Novartis is launching a phase 3 trial of gene therapy Zolgensma that could open up a “multibillion-dollar” indication in older spinal muscular atrophy patients. (Novartis)

As Novartis' gene therapy Zolgensma makes inroads in newborns diagnosed with spinal muscular atrophy, the company is looking to expand the drug’s reach to older patients with a new formulation. After a safety scare and a regulatory setback, the Swiss pharma is now back on track with that plan.

The FDA has lifted a partial clinical hold on a spinal injection formulation of Zolgensma, Novartis said Tuesday. With that roadblock out of the way, Novartis plans to start a registrational phase 3 trial to evaluate the treatment in spinal muscular atrophy (SMA) patients between 2 and 18 years of age, the company said.

Zolgensma is currently administered through an intravenous infusion, and, in the U.S., it’s only allowed to treat children younger than 2. The new intrathecal version could more than double Zolgensma’s eligible patient pool, and as Novartis CEO Vas Narasimhan has put it, represents a “multibillion-dollar” indication.

But the company's expansion plan hit a setback in 2019 when the FDA slapped a partial hold on a phase 1/2 trial of intrathecal Zolgensma after preclinical tests flagged a risk for spinal cord inflammation in animal studies. The low- and mid-dose cohorts of the trial had already completed interim analysis at that time.

RELATED: Novartis' Zolgensma expansion hits FDA roadblock, giving Biogen and Roche a reprieve

While Novartis had hoped that it could seek approval based on the available phase 1/2 data, the FDA rejected that proposal last September, requiring the company to run a controlled phase 3 study. With the clinical hold in place, Novartis couldn’t proceed with that pivotal trial—until now.

After reviewing additional toxicology data from monkeys, the FDA concluded that Zolgensma’s intrathecal clinical program is safe to move forward. The phase 3 trial, dubbed Steer, aims to enroll more than 100 treatment-naïve patients with Type 2 SMA between 2 and 18 years of age who are able to sit but have never walked.

Investigators aim to see whether the one-time gene therapy can help improve outcomes for patients on a motor function scale versus sham control after 52 weeks.

RELATED: Novartis touts latest Zolgensma data as SMA competition against Biogen, Roche heats up

As part of its launch efforts for Zolgensma, Novartis is currently pushing for newborn screening to identify SMA patients early before symptom onset. In the U.S., 80% of newborns are being screened, allowing treatment to start within a few weeks of birth, Novartis pharma chief Marie-France Tschudin told investors during a call two weeks ago. In Europe, the Swiss pharma is making progress market by market after its approval there last May, she said. It’s targeting 20% of overall screening rate in the EU by the end of 2021.

Thanks to geographic expansion and new reimbursement deals in Europe, Zolgensma grew sales by 48% year over year to $315 million in the second quarter.

But competition is heating up. 

Roche last year introduced an oral SMA option, Evrysdi, which is allowed for a broad patient population two months of age and older. Industry watchers mainly see it as a threat to Biogen’s Spinraza, which is administered intrathecally.