FDA Approves First Intrathecal Gene Therapy for Spinal Muscular Atrophy Across All Ages
核心洞察
The FDA has approved Itvisma (搜索) (onasemnogene abeparvovec-brve (搜索)), the first intrathecally administered gene therapy for spinal muscular atrophy, expanding treatment options for children, teens, and adults with SMA.
The approval was based on positive results from the phase 3 STEER study, where patients receiving intrathecal treatment showed a statistically significant 2.39-point improvement on motor function scales compared to 0.51 points for sham treatment.
This one-time gene replacement therapy addresses the genetic root cause of SMA by providing a functional copy of the SMN1 (搜索) gene, potentially reducing the need for chronic treatment in approximately 9,000 Americans living with this rare neuromuscular disease.
Novartis has secured FDA approval for Itvisma (搜索) (onasemnogene abeparvovec-brve (搜索)), marking the first intrathecally administered gene therapy for spinal muscular atrophy (SMA). The approval expands treatment options for patients two years of age and older living with SMA who have a confirmed mutation in the survival motor neuron (搜索) 1 gene.
The gene therapy represents a significant advancement in SMA treatment, as it addresses the genetic root cause of the disease by providing a functional copy of the human SMN1 (搜索) gene. This one-time dose replaces the SMN1 gene and potentially reduces the need for chronic treatment, according to Novartis.
Clinical Trial Results Drive Approval
The FDA's approval was primarily based on positive data from the phase 3 STEER study, a 52-week trial that enrolled 126 treatment-naïve patients with SMA Type 2. Participants were randomly assigned 1:1 to either receive Itvisma (搜索) or undergo a sham procedure, followed by a crossover phase.
In the trial, patients receiving the intrathecal medication demonstrated a statistically significant 2.39-point improvement on the Hammersmith Functional Motor Scale-Expanded (HFMSE) compared to 0.51 points for those receiving sham treatment (P = .0074). While all secondary endpoints consistently favored Itvisma (搜索), they did not achieve statistical significance due to the pre-planned multiple testing procedure.
Supportive findings from the ongoing phase 3b STRENGTH study also contributed to the approval decision. This open-label, single-arm study included 27 patients with a mean age of 7.4 years who had discontinued previously approved treatments nusinersen (Spinraza) or risdiplam (Evrysdi). Over the 52-week period, patients demonstrated a least square mean increase of 1.05 points in HFMSE, considered a stabilization.
Safety Profile and Adverse Events
The intrathecal formulation maintained a similar safety profile to that observed in previous studies. In the STRENGTH trial, the most frequent adverse events were common cold, pyrexia, and vomiting, with 13 patients (48.1 percent) experiencing treatment-related events. Notably, no adverse events led to death or study discontinuation.
Additional safety data from the STRONG study, which tested three dose levels across different age groups, showed that the treatment was generally safe with no deaths reported. All participants experienced at least one treatment-emergent adverse event, most commonly upper respiratory infection, pyrexia, cough, vomiting, and constipation.
Addressing Unmet Medical Need
Spinal muscular atrophy is a rare, genetic neuromuscular disease caused by a mutated or missing SMN1 (搜索) gene. The gene produces most of a protein needed by the body for muscle function, including breathing and basic movement. Approximately 9,000 people in the United States live with spinal muscular atrophy.
"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 Day, MD, PhD, professor of neurology and pediatrics and 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."
Impact on Patient Care
The approval provides a new administration route for patients who may benefit from gene therapy but were previously limited by intravenous delivery options. Kenneth Hobby, president at Cure SMA, emphasized the broader implications beyond clinical measurements: "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 intrathecal formulation represents an evolution from the original onasemnogene abeparvovec, which was first approved in 2019 as a single intravenous infusion. This adeno-associated virus vector-based medication is designed to improve motor function through sustained survival motor neuron (搜索) (SMN) protein expression.