Onasemnogene abeparvovec

Novartis’ Itvisma (onasemnogene) has been approved by the US FDA to treat spinal muscular atrophy (SMA) in children aged two years and older, teenagers and adults with a confirmed mutation in the survival motor neuron 1 (SMN1) gene. SMA is a rare, genetic neuromuscular disease caused by a mutated or missing SMN1 gene. Since the SMN1 gene is directly responsible for producing the SMN protein needed for muscle function, including movement, breathing and swallowing, problems with this gene can cause progressive and debilitating muscle weakness. Around 9,000 people in the US currently live with SMA. Itvisma is designed to provide a functional copy of the SMN1 gene, thereby boosting SMN protein expression and improving motor function. While many other available SMA therapies need to be administered regularly, Itvisma can be given as a single injection that does not need to be adjusted for age or body weight. “The FDA’s approval of intrathecal onasemnogene abeparvovec is a game-changing advance, expanding the use of transformational gene replacement therapy for SMA across age groups,” said John W Day, director of the Division of Neuromuscular Medicine at Stanford University School of Medicine. “This achievement is not only a significant step forward for SMA – it also signals new possibilities for the broader field of neurological disorders and genetic medicine.” The approval of Itvisma is based on data from two phase 3 studies, in which the treatment showed statistically significant improvements in motor function and stabilisation of motor abilities. These effects were sustained over 52 weeks of follow-up. Kenneth Hobby, president of Cure SMA, said: “This new route of administration for a single dose of gene replacement therapy can mean so much more than what is measured by numbers on a functional motor scale – it could mean greater independence and freedom in activities of daily life. “The SMA disease landscape has dramatically changed over the last six years, when the first gene therapy was approved. This is another welcome advancement.”

Like Zolgensma, Novartis' Itvisma is a one-time treatment that delivers a functional copy of the human SMN gene to treat SMA. Novartis has received an FDA approval for Itvisma, a new version of the company’s gene therapy Zolgensma, to treat older patients with spinal muscular atrophy (SMA).The approval comes more than six years after the FDA first cleared Zolgensma for SMA patients under 2 years old. Itvisma now covers all older patients with a confirmed mutation in the SMN1 gene.Both therapies work by delivering a functional copy of the human SMN gene via adeno-associated virus (AAV) vectors. While their active drug substances are identical, Itvisma is given directly to the central nervous system via an intrathecal injection in the spinal cord area, whereas Zolgensma is administered intravenously. Thanks to that formulation, Itvisma can be given to patients with larger weight in a more concentrated dose.Novartis is pricing Itvisma at a wholesale acquisition cost of $2.59 million, a company spokesperson told Fierce Pharma. At that price, the one-time therapy costs 35% to 46% less than existing chronically dosed treatments over the span of 10 years, according to the spokesperson.Patients’ out-of-pocket cost may vary, although Novartis expects broad coverage, the spokesperson added. The company is offering a patient support program in which eligible individuals may pay as little as $0.About 9,000 people in the U.S. live with SMA, and the majority of them are older children, teens and adults, Tracey Dawson, Ph.D., Novartis’ head of U.S neuroscience business, said in an interview with Fierce Pharma ahead of the approval.Given the broader patient population, Novartis has projected multibillion-dollar peak sales for Itvisma, also known as OAV101 IT. Since its initial approval in 2019, Zolgensma has treated more than 5,000 patients globally. Last year, the intravenous therapy brought in sales of $1.2 billion, making it the world’s best-selling gene therapy. Itvisma is geared toward patients who’re considering an option that may free them from the burden of chronic treatment, Dawson said. Novartis expects many of Itvisma’s recipients to be switching from existing therapies such as Biogen’s Spinraza and Roche’s Evrysdi, she said.Itvisma proved its worth in that population in the phase 3b Strength trial. Among 27 patients who discontinued treatment with either Spinraza or Evrysdi, their motor function, as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE) score, showed stabilization over one year after receiving Itvisma. For the 66-point assessment, patients on Itvisma saw an increase in HFMSE least squares score of 1.05 by one year.The intrathecal gene therapy also works in treatment-naïve patients. In the Steer study, Itvisma showed a statistically significant 2.39-point improvement on the HFMSE, versus 0.51 points in patients who got a sham treatment.“While the numbers might not look huge, what it means from a clinical impact to a patient is that they’re able to continue to use their wheelchair controls, or they’re able to continue to walk,” Dawson said.Some of the seemingly tiny improvements, such as being able to keep grip strength, are meaningful to SMA patients, she said.To counter newer SMA options, Biogen has developed a higher-dose version of Spinraza. The new formulation just scored backing from the Committee for Medicinal Products for Human Use of the European Medicines Agency, setting up for a marketing authorization from the European Commission. Following a complete response letter in September related to certain technical information request, the FDA has accepted a resubmission from Biogen and has set a target decision date for high-dose Spinraza on April 3, 2026. Novartis is investing heavily in neuromuscular diseases lately. The Swiss pharma is shelling out about $12 billion to acquire Avidity Biosciences. The deal would give Novartis an RNA-based platform that produces antibody oligonucleotide conjugates, plus three late-stage muscular dystrophy programs.The deal follows another smaller acquisition a year ago of AAV gene therapy specialist Kate Therapeutics, which leverages in vivo expression of transgene RNA.