3.1 Onasemnogene abeparvovec (Zolgensma; Novartis Gene Therapies) is a gene therapy medicinal product that expresses the human survival motor neuron (SMN) protein. It is a non-replicating recombinant viral vector (adeno-associated vector serotype 9; AAV9) modified to contain the cDNA of the human SMN gene. When infused, the vector is expected to carry a functional copy of the SMN1 gene into the motor neurons. This provides an alternative source of SMN protein expression in these cells, which is expected to promote the survival and function of the motor neurons that contain the vector.
3.2 Onasemnogene abeparvovec is administered as a single-dose intravenous infusion and the effects are thought to be lifelong. The dose volume is 1.1×1014 vector genome copies per kilogram. Baseline laboratory testing is needed before administering onasemnogene abeparvovec, as detailed in section 4.2 of the summary of product characteristics. It has a conditional marketing authorisation in the UK for treating '5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA Type 1, or 5q SMA with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the SMN2 gene'.
3.3 The adverse reactions listed in the summary of product characteristics for onasemnogene abeparvovec include: thrombocytopenia, vomiting, pyrexia and an increase in transaminases, aspartate aminotransferase, alanine aminotransferase and troponin‑I. For full details of adverse reactions and contraindications, see the summary of product characteristics.
3.4 The summary of product characteristics states that: 'there is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of onasemnogene abeparvovec in these patients have not been established.'
3.5 The price for onasemnogene abeparvovec is £1,795,000 (excluding VAT; company submission). The company has a commercial arrangement. This makes onasemnogene abeparvovec available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.