Novartis must stop enrollment of a clinical trial testing its gene therapy for a rare, muscular disorder after safety concerns surfaced in data from an animal study.
The FDA put a partial clinical hold on a Phase 1/2 study testing the therapy, Zolgensma, Novartis (NYSE: NVS) announced Wednesday. The decision doesn’t halt the study entirely; it means that no new patients can be added. But it’s another blemish on the therapy, coming months after an FDA finding that some of the animal data used to support the approval of Zolgensma was manipulated. Novartis says the partial hold does not affect Zolgensma already on the market.
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Zolgensma was approved in May, becoming the second gene therapy to win the FDA’s nod. The therapy treats spinal muscular atrophy (SMA), a disorder in which a genetic defect leads to the loss of nerve cells in the spinal cord and brain stem. The disease causes muscles to waste away, leading to paralysis. SMA is categorized by several subtypes depending on the severity of the disease. The FDA approval of an intravenously administered version of the therapy covers children under 2 regardless of SMA subtype, as long as their disease was confirmed via newborn screening.
Novartis has been testing doses of its therapy given as an infusion into the spine, studies intended to support approval of the therapy in older children. The company will need that approval in order to compete against nusinersen (Spinraza), a drug developed by San Diego’s Ionis Pharmaceuticals (NASDAQ: IONS) and Biogen (NASDAQ: BIIB). The drug, which is administered as an injection into the fluid surrounding the spinal cord, won FDA approval in 2016 for all types of SMA in patients of all ages.
The FDA issued its partial hold on the Zolgensma study after Novartis subsidiary AveXis notified health authorities and clinical trial investigators that an animal study showed inflammation in cells in the dorsal root of the spinal nerve, according to the Swiss pharmaceutical giant. That inflammation was sometimes accompanied by degeneration or loss of nervous system cells. In a statement, Novartis says the significance of this inflammation to patients in the clinical trial is not known, but it was not observed in earlier animal studies testing the gene therapy. The company adds that this inflammation can be associated with “sensory effects,” but no such effects or problems have been found in data from tests of the therapy in humans.
The partial hold means that Novartis can’t enroll more patients in the group being tested with the high dose of the therapy. The company says that the low- and mid-dose groups have completed enrollment and produced preliminary data.
Novartis says it remains confident that Zolgensma offers patients more benefit than risk, and it will continue tests of an intravenously administered version of its gene therapy. The company adds that it will work with the FDA to determine what needs to be done in order to resume tests of the version of its gene therapy administered by spinal infusion.