Novartis publishes long-term data from SMA gene therapy

Novartis has produced data demonstrating its Zolgensma gene therapy produces long term benefits in the rare muscle wasting disease spinal muscular atrophy – information that will be closely monitored by payers wanting a return on their investment in the world’s most expensive drug.

Zolgensma (onasemnogene abeparvovec-xioi) costs more than $2.1 million for a single shot in the US, but Novartis hopes the drug developed by its Avexis unit will permanently correct the genetic defect that causes SMA and allow affected people to live normal lives.

Trial data were published as the Japanese regulator approved Zolgensma for SMA patients under the age of two.

SMA is a rare genetic disease that causes muscle weakness, decreased muscle tone, breathing problems, problems eating and swallowing, and babies with the most serious form of the disease often die within the first few years of life.

Data from the STR1VE-US study were presented during a session conducted by the Muscular Dystrophy Assocation, scheduled after its 2020 annual conference was cancelled due to COVID-19

There were also posters for the SPR1NT and START long-term follow up trials, and the MDA said it would publish cumulative data online in the coming weeks.

Interim data from the ongoing SPR1NT study continue to show patients achieved age-appropriate motor milestones when treated with Zolgensma before symptoms showed.

Most patients (7/8) with two copies of SMN2 who achieved the ability to sit independently did so within the World Health Organization window of normal development. The six remaining patients in this cohort of 14 patients have not yet passed the developmental window.

Sitting is an important milestone as it is a gateway for development and integration of cognitive, sensory and motor skills that are important for functional independence and social development.

Noavrtis said nearly all patients were fed orally and required no feeding support. Most remained within the age-appropriate weight range. No patients required ventilatory support of any kind.

STR1VE-US is now completed and formed the basis of regulatory filings for Zolgensma, and data showed 20 of 22 patients (91%) met the co-primary efficacy endpoint of event-free survival at 14 months, and 13 of 22 patients (59%) met the co-primary efficacy endpoint of functional sitting for ≥30 seconds at 18 months of age.

Thirteen patients managed to sit for 30 seconds or more at the age of 18 months at the first study visit, and a fourteenth patient achieved the sitting milestone at 16 months, although this was not confirmed at the 18 month visit.

Fifteen patients (68%) did not require non-invasive ventilatory support at any point during the study. Eighteen of 22 patients (82%) did not use ventilatory support at 18 months.

STR1VE-US also had a more stringent “ability to thrive” endpoint, including swallowing, feeding, and maintaining the right age-related weight.

Of the 22 patients in the trial, nine (41%) achieved this goal at 18 months in the trial that used natural history as a comparator arm.

There was also long-term follow-up data from the phase 1 START study in SMA type 1 patients, which showed that at the end of the 24-month study all 12 patients in a cohort taking the targeted therapeutic dose were alive and free of permanent ventilation.

Ten of these 12 patients enrolled in an ongoing observational long-term follow-up of the START study.

Novartis said that six out of ten patients do not require treatment with Biogen’s Spinraza (nusinersen), another hugely expensive drug for SMA.


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