P.342Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene – evaluation through a managed access agreement

Abstract

About 10-15% of Duchenne muscular dystrophy (DMD) patients have a nonsense mutation. The drug Ataluren is a mutation specific therapy developed by PTC therapeutics to target this mutation to treat the underlying cause of DMD. Based on the clinical and economic evidence from the evaluation of the drug, and the significance of the benefits placed by patients, carers and clinical experts, a managed access agreement (MAA) was established with NICE, NHS England, PTC therapeutics, patient community and clinical experts to evaluate the long term effects of the drug and review continued use of the treatment. The Northstar clinical network collects and holds the data for review for this MAA. This abstract aims to describe the characteristics of the current patient cohort in the MAA. The MAA enrols DMD patients with nonsense mutation aged 5 years and over who are able to walk 10 steps unaided, from 15 centres across England. Upon signing the MAA consent, Ataluren is prescribed to patients with the criteria to stop the treatment within six months of reaching a non-ambulatory status. Patient's age, steroid use, NSAA, quality of life data (CUH9, EQ5D) and details of the drug are collected at six monthly intervals. 77 patients have been enrolled into the MAA since August 2016. At enrolment (baseline), the mean age of the patients was 8 years, 56 patients were on an intermittent or daily regime of steroids, with an average of 41 months of steroid use. The mean NSAA at baseline was 20.7. This is an observational study without randomisation. Propensity score matching will be used to minimise bias in comparing the change in the NSAA total score, over a 4-year period between the Ataluren cohort and concurrent control patients. Baseline matching factors will include age, steroid use duration (< 1 year, or >1 year), steroid regimen, steroid type, and baseline NSAA total score; with an aim for a 1-1 match. Availability of Ataluren as treatment for DMD in the NHS will be based on the findings of this MAA, and subsequent recommendations from NICE.