Evaluating the Efficacy and Safety of Transitioning Patients from Natalizumab to Ocrelizumab (OCTAVE)

Objective: To present interim data from OCTAVE, a prospective, observational study to evaluate the efficacy and safety of OCR in RMS patients previously treated with NTZ. Background: Natalizumab (NTZ) is an effective therapy for patients with relapsing MS (RMS). However, it is associated with a risk of progressive multifocal leukoencephalopathy (PML) in patients infected with John Cunningham virus (JCV). Ocrelizumab (OCR) has demonstrated efficacy, yet its safety in patients previously treated with NTZ is unclear. Design/Methods: Clinically and radiologically stable RMS patients, aged 18–65 treated with NTZ for ≥ 12 months, were started on OCR 4–6 weeks after last dose of NTZ and followed for 12 months. Relapse assessment, Expanded Disability Status Scale (EDSS), and MRI were performed prior to starting OCR and at months 3, 6, 9 (no MRI), and 12 Results: Twenty-one patients, 71.4% female with mean age of 43.7 (±10.6), baseline EDSS of 3.4 (±1.5), and 12.4 (±1.2) NTZ infusions in the 12 months prior have been enrolled between August 2017 and September 2018. Seventeen subjects switched to OCR due to potential PML risk. None of the 16 patients assessed at 6 months discontinued OCR or had a relapse. EDSS and imaging were stable, except for one patient with 3 new T2 lesions. Physical and psychological MSIS-29 improved slightly from 42.1 to 40.7 and 20.1 to 18.6 respectively. Infusion reactions were seen in 38% of patients with the first dose and 12.5 % with the second dose. Four serious adverse events (SAEs) have been reported with two possibly related to OCR, breast cancer and acute cystitis. No cases of PML reported. Conclusions: The absence of relapses, EDSS progression, and MRI changes to date are encouraging; however, the two possibly related SAEs are concerning given the small number of patients. Disclosure: Dr. Smoot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sanofi Genzyme, Genentech, EMD Serono, Novartis Pharmaceuticals, and Teva. Dr. Smoot has received research support from Biogen and Genentech. Dr. Chen has nothing to disclose. Dr. Gervasi has nothing to disclose. Dr. Lucas has nothing to disclose. Dr. Kresa-Reahl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, EMDSerono, Genentech, Sanofi Genzyme, TEVA, Novartis Pharmaceuticals, and Celgene. Dr. Kresa-Reahl has received research support from Biogen, EMDSerono, Genentech, Genzyme, Novartis Pharmaceuticals, and Celgene. Dr. Repovic has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Genentech, EMD Serono. Dr. Craddock has nothing to disclose. Dr. Cohan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme, Biogen, Acorda, Genentech, Novartis, Mallinckrodt. Dr. Cohan has received research support from Biogen, Mallinckrodt, Novartis, Roche Genentech, Sanofi Genzyme, MedDay.