Novartis has announced positive top-line results from its Phase 3 STEER study evaluating intrathecal onasemnogene abeparvovec (OAV101 IT) for spinal muscular atrophy (SMA) type 2. The study focused on treatment-naïve patients aged two to less than 18 years who could sit but had never walked independently, comparing results against a sham control.
Novartis's SMA Gene Therapy Shows Promise
The STEER study assessed the efficacy of OAV101 IT in a specific subset of SMA patients. SMA is a rare neuromuscular disease characterized by muscle weakness and atrophy. The investigational gene therapy aims to address the underlying genetic defect by delivering a functional copy of the SMN1 gene directly to the central nervous system via intrathecal administration. Detailed results from the study are expected to be presented at an upcoming medical conference.
India's First Gene Therapy for Hemophilia-A
In India, a significant medical breakthrough has been achieved with the successful application of the country's first human gene therapy for severe hemophilia-A. Developed by the Centre for Stem Cell Research (CSCR) at CMC, Vellore, with support from the Department of Biotechnology, the lentiviral vector-based therapy has demonstrated a zero bleeding rate in the initial phase trial involving five patients aged between 22 and 41. Hemophilia-A, a serious bleeding disorder caused by a deficiency in clotting factor VIII, can lead to spontaneous bleeding episodes and joint damage. The annualized bleeding rate was observed to be zero in all five patients over a cumulative follow-up of 81 months, marking a substantial improvement in their quality of life.
Novel Prenatal Gene Therapy Technique
Researchers have developed a new gene therapy technique that aims to deliver treatment before birth. This innovative approach utilizes a novel delivery system for sending CRISPR reagents to brain cells, enabling gene editing. The nanoparticle-based method exposes cells to the instructions for building CRISPR reagents and the correct gene sequence to repair a gene defect. The goal is to repair genetic problems at very early stages of development, potentially preventing the onset of genetic diseases. While still in the early stages of research, investigators are optimistic about the potential of this technique for treating human patients identified during prenatal testing.
Safety Concerns Addressed in Other Gene Therapy Trials
Recent scrutiny has been directed towards Bluebird bio's Skysona (elivaldogene autotemcel) following reports of blood cancer cases in gene therapy trials. Data published in The New England Journal of Medicine revealed that seven out of 67 patients under 18 years of age who participated in Phase II and Phase III trials for Skysona developed hematologic cancers. Skysona is a one-time autologous hematopoietic stem cell-based gene therapy used to treat early cerebral adrenoleukodystrophy (CALD), a rare and fatal neurodegenerative disease. These findings underscore the importance of long-term monitoring and safety assessments in gene therapy trials.
Neurogene also faced a setback when a patient died in a clinical trial of its Rett syndrome gene therapy, NGN-401. Despite this, the FDA is allowing the Phase 1/2 study to continue with a lower dose, highlighting the complexities and risk-benefit assessments involved in gene therapy development for rare diseases.
