Novartis Secures FDA Approval of ITVISMA for Children Two Years and Older, Teens, and Adults with Spinal Muscular Atrophy (SMA)
Novartis has announced a significant expansion in the treatment landscape for Spinal Muscular Atrophy (SMA) with the FDA approval of ITVISMA (onasemnogene abeparvovec-brve). This one-time gene replacement therapy is now approved for children two years and older, teens, and adults with a confirmed mutation in the Survival Motor Neuron 1 (SMN1) gene.
SMA is a devastating, rare, genetic neuromuscular disorder caused by a missing or mutated SMN1 gene, leading to deficient SMN protein production, progressive motor neuron loss, muscle weakness, and paralysis.
ITVISMA, a formulation of the active ingredient in ZOLGENSMA (Novartis’s existing gene therapy for SMA patients under two), is administered via a single intrathecal injection into the cerebrospinal fluid surrounding the spinal cord. This unique route of administration allows for the targeted delivery of a functional copy of the SMN1 gene to the motor neurons, the disease’s primary site of action, without the need for weight-based dosing adjustments required by its intravenous counterpart.
The approval is supported by data from the Phase III STEER study and the STRENGTH study, which demonstrated statistically significant improvements in motor function and stabilization of motor abilities over 52 weeks, regardless of a patient’s prior SMA treatment history. This development is hailed as a game-changing advance by experts and patient advocates, as it addresses a substantial unmet need for older patients by providing a durable, one-time treatment that aims to halt further disease progression and potentially reduce the need for chronic SMA therapies.
Kelun-Biotech’s Phase III Study Shows Sac-TMT + Keytruda Achieves Primary Endpoint in First-Line PD-L1-Positive NSCLC
Kelun-Biotech, in partnership with Merck & Co. (MSD) outside of Greater China, has achieved a critical milestone in oncology. The company announced that its registrational Phase III OptiTROP-Lung05 trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS).
The study evaluated the novel TROP2-directed antibody-drug conjugate (ADC), Sac-TMT (sacituzumab/ tirumotecan), in combination with MSD’s blockbuster PD-1 inhibitor, Keytruda (pembrolizumab), versus Keytruda monotherapy. The trial focused on treatment-naïve patients with locally advanced or metastatic PD-L1-positive non-small cell lung cancer (NSCLC).
This achievement marks the first Phase III clinical trial globally of an ADC combined with an immune checkpoint inhibitor to meet its primary endpoint in the challenging first-line NSCLC setting. The combination therapy also showed a positive trend in overall survival (OS) at the pre-specified interim analysis.
Sac-TMT is a proprietary ADC designed to deliver a potent cytotoxic payload directly to tumor cells expressing the TROP2 antigen, inducing DNA damage and apoptosis. When combined with KEYTRUDA, which boosts the patient’s immune response against cancer, the therapy targets the disease through complementary mechanisms: direct cell killing and immunomodulation. This successful combination represents a potential paradigm shift for first-line PD-L1-positive NSCLC, moving the field toward highly effective targeted combination regimens that could improve patient outcomes.
Evoke Phase 3 Trials Failed to Show a Statistically Significant Impact on Alzheimer’s Disease Progression
The search for effective disease-modifying therapies for Alzheimer’s Disease (AD) faced a significant setback as the Phase III EVOKE and EVOKE+ trials, sponsored by Novo Nordisk, failed to meet their primary endpoint. The trials investigated the efficacy and safety of oral semaglutide, a GLP-1 receptor agonist widely known for its use in diabetes and obesity, in slowing the progression of early symptomatic AD.
The randomized, double-blinded studies, which enrolled over 3,800 adults with mild cognitive impairment or mild dementia due to AD, compared oral semaglutide to placebo on top of standard care. The primary endpoint measured the reduction in AD progression using the change in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score from baseline over two years.
Topline results indicated that semaglutide did not demonstrate superiority to placebo in reducing the rate of clinical progression. Although the drug improved specific AD-related biomarkers in both trials, this improvement did not translate into a statistically significant delay in disease progression.
In response to the data, Novo Nordisk has decided to discontinue the planned one-year extension periods of the trials. While the outcome is disappointing for the AD community, the company noted that the drug’s safety profile remained consistent with that observed in previous semaglutide trials. The failure underscores the complexity of AD pathobiology. While metabolic and inflammatory pathways targeted by GLP-1 agonists are relevant to the disease, they may not be sufficient as a monotherapy to alter clinical decline significantly.
Sangamo Therapeutics Announces FDA Acceptance of BLA Rolling Submission Request for ST-920 in Fabry Disease
Sangamo Therapeutics has achieved a key regulatory milestone in the development of its investigational gene therapy, ST-920 (isaralgagene/civaparvovec), for Fabry disease. The FDA has accepted Sangamo’s request for a rolling submission and review of the Biologics License Application (BLA) under the accelerated approval pathway.
Fabry disease is a rare, life-threatening, X-linked lysosomal storage disorder caused by a mutation in the galactosidase alpha (GLA) gene, leading to a deficiency of the alpha-galactosidase A (α-Gal A) enzyme. This deficiency leads to the harmful accumulation of globotriaosylceramide (Gb3) in vital organs such as the heart and kidneys.
ST-920 is a one-time, wholly owned gene therapy designed to address the underlying genetic cause of the disease. The BLA submission will be supported by clinical data from the registrational Phase 1/2 STAAR study, which demonstrated the gene therapy’s potential for durable alpha-Gal A enzyme activity. Crucially, the FDA has agreed to use the mean annualized estimated glomerular filtration rate (eGFR) slope at 52 weeks as a primary basis for accelerated approval, providing a measurable clinical endpoint for kidney function.
The acceptance of the rolling submission allows Sangamo to submit completed sections of the BLA to the FDA for review on an ongoing basis rather than waiting for the entire application to be completed. This streamlined process expedites the potential approval of ST-920, offering hope of a transformative single-infusion treatment option for patients with Fabry disease.
U.S. FDA grants accelerated approval to Bayer’s HYRNUO (sevabertinib) for Patients with Previously Treated Advanced HER2-mutant Non-small Cell Lung Cancer
Bayer has received Accelerated Approval from the U.S. FDA for HYRNUO (sevabertinib), a new, oral, reversible tyrosine kinase inhibitor (TKI), for the treatment of adult patients with previously treated, locally advanced or metastatic non-squamous NSCLC whose tumors harbor an activating HER2 mutation.
Activating HER2 mutations, particularly exon 20 insertions, occur in 2–4% of advanced NSCLC cases and are associated with a poor prognosis and limited treatment options. The FDA granted the approval based on compelling data from the Phase I/II SOHO-01 trial, which evaluated sevabertinib in patients who had progressed after at least one prior systemic therapy.
In patients naive to HER2-targeted therapy, sibertinib demonstrated robust and durable anti-tumor responses, achieving an impressive Objective Response Rate (ORR) of 71% and a median Duration of Response (DOR) of 9.2 months. These results highlight sevabertinib’s targeted mechanism of action, which potently inhibits the mutant HER2 receptor while maintaining high selectivity.
The accelerated approval pathway allows conditional approval of therapies that address severe conditions and fill an unmet medical need based on a surrogate endpoint (such as ORR) that is reasonably likely to predict clinical benefit. This regulatory decision, which followed Breakthrough Therapy and Priority Review designations, provides a much-needed, targeted oral option for this genetically defined subset of lung cancer patients, elevating the standard of care for a challenging disease.
