Novartis gene therapy poised to expand SMA treatment landscape, says GlobalData
Novartis has recently announced that its intrathecal (IT) formulation of onasemnogene abeparvovec (OAV101 IT) successfully achieved the primary endpoint in a Phase III STEER study (NCT05089656) involving pediatric patients aged 2–17 years with type II spinal muscular atrophy (SMA). These positive results have the potential to broaden the eligible patient population for this gene transfer therapy, according to GlobalData, a leading data and analytics company.
GlobalData’s report, “Spinal Muscular Atrophy: Opportunity Assessment and Forecast,” reveals that the combined sales of IT and intravenous (IV) formulations of onasemnogene abeparvovec are projected to increase from $660.6 million in 2023 to $763.8 million by 2033 in the seven major markets (*7MM) due to the growing awareness of SMA and the implementation of newborn screening (NBS) across the markets, coupled with an increase the eligible population for gene transfer therapy.
Novartis’ Zolgensma, an IV formulation of onasemnogene abeparvovec, received FDA approval in 2019 and represents the first and only gene transfer therapy for the treatment of SMA. However, the eligible patient population indicated for Zolgensma is restricted to pediatric patients less than two years of age with SMA with biallelic mutations in the survival motor neuron 1 (SMN1) gene.
In the STEER study, OAV101 IT demonstrated clinical benefit in treatment-naïve type II SMA patients ages 2-17, who were able to sit but had never walked independently. In addition, the safety profile of OAV101 IT was favorable, with overall adverse events and serious adverse events comparable in the investigational and control arms. The most common adverse events were upper respiratory tract infection, pyrexia, and vomiting.
Christie Wong, Managing Neurology Analyst at GlobalData, comments: “However, safety concerns have previously been raised with OAV101 IT. In 2019, the FDA implemented a partial clinical hold on OAV101 IT due to a preclinical study in which animal findings showed dorsal root ganglia mononuclear cell inflammation, which was sometimes accompanied by neuronal cell body degeneration or loss. However, the clinical hold was lifted on OAV101 IT in August 2021, based on non-clinical data from a toxicology study in non-human primates that addressed safety concerns.”
Novartis plans to share STEER results with regulatory agencies including the FDA in 2025. If approved, OAV101 IT could broaden the patient population eligible for gene transfer therapy to include type II SMA patients under 18 years of age.
Wong adds: “The key opinion leaders (KOLs) previously interviewed by GlobalData noted that the implementation of NBS initiatives in their countries has greatly facilitated disease detection during the pre-symptomatic stage and has enabled many eligible patients to receive Zolgensma. The availability of OAV101 IT would be most beneficial to patients where NBS for SMA is not yet adopted in their country and/or patients who received a delayed diagnosis.”
KOLs added that OAV101 IT would be welcomed by patients due to its treatment convenience of a one-time infusion, compared to Biogen’s once-quarterly IT administration of Spinraza (nusinersen) and Roche’s once-daily Evrysdi (risdiplam).
Wong concludes: “If approved, OAV101 IT could significantly enhance patient outcomes in markets where NBS or early diagnosis remains a challenge.”
*7MM = The US, France, Germany, Italy, Spain, the UK, and Japan.
