Author Of 2 Presentations
P0218 - Long-term safety, compliance, and effectiveness of ofatumumab in patients with relapsing multiple sclerosis: ALITHIOS Phase 3b study (ID 1580)
Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide along with a favorable safety profile in the Phase 3 ASCLEPIOS trials in relapsing multiple sclerosis (RMS) patients. Assessment of the long-term use of subcutaneous (s.c.) ofatumumab 20 mg is important to further understand its benefit-risk profile.
To present the design of the ALITHIOS extension study of ofatumumab and evaluate treatment compliance, including treatment discontinuations, in patients transitioning to the ALITHIOS study.
ALITHIOS is an ongoing Phase 3b, open-label, umbrella extension study which has enrolled eligible patients (approximately 1700 patients) completing the Phase 3 ASCLEPIOS I/II, Phase 2 APOLITOS and APLIOS trials from >300 sites worldwide. ALITHIOS consists of three parts: screening, loading, and open-label treatment. Ofatumumab 20 mg is administered at the site on Day 1 (patients from ASCLEPIOS have a blinded loading part with two additional ofatumumab/matching placebo s.c. injections on Days 7 and 14; no blinding is required for those from the APOLITOS and APLIOS studies) followed by open-label treatment every 4 weeks from Week 4 for up to 5 years. The primary endpoint is the proportion of patients with adverse events (AEs); abnormal laboratory, vital signs or electrocardiogram results; and the proportion of patients meeting predefined criteria of suicidal behavior as per the Columbia Suicide Severity Rating Scale. Secondary endpoints include relapse rate, disability (worsening and improvement), and magnetic resonance imaging outcomes. Patient-reported outcomes was included as an exploratory endpoint. The proportion of eligible patients who accepted transition to ALITHIOS from the Phase 2/3 trials and treatment compliance (defined as exposure to study drug [days]/duration of on-treatment period [days]×100%) are recorded.
As of May 2020, 1692 patients from 37 countries and 294 sites were screened, and 1671 (98.8%) were enrolled into ALITHIOS; 1615 patients are ongoing and 56 (3.3%) patients discontinued. The most common reasons for discontinuation were patient/guardian decision (0.9%), AEs (0.5%), and physician decision (0.2%). The study is expected to complete in 2025. Study design details and compliance data will be presented at the congress.
The ALITHIOS study is designed to allow patients who participated in prior ofatumumab studies to continue with the treatment, and to further assess the benefit-risk profile of ofatumumab in RMS and tolerability in long-term use.
P0236 - Serum immunoglobulin levels and infection risk in the Phase 3 trials of ofatumumab in relapsing multiple sclerosis (ID 1566)
Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy vs teriflunomide with a favorable safety profile in relapsing MS (RMS) patients in the Phase 3 ASCLEPIOS I/II trials. Reductions in serum immunoglobulin (Ig) M and IgG levels are associated with anti-CD20 therapies.
To assess the effect of ofatumumab on serum Ig levels and evaluate potential association between a decrease in IgM/IgG levels and risk of infections.
Patients were randomized to receive subcutaneous ofatumumab 20 mg (initial doses: Days 1, 7, and 14; subsequent doses: every 4 weeks from Week (W) 4 onwards) or oral teriflunomide 14 mg once-daily for up to 30 months (m, mean follow-up duration: 18m). Serum IgM/IgG levels were monitored at baseline (BL), W4, W12, and every 12 weeks thereafter (ofatumumab, n=946; teriflunomide, n=936). Proportion of patients with IgM/IgG levels below the lower limit of normal (<LLN [g/L]: IgM, 0.4; IgG, 7.0), and association of IgM/IgG levels with incidence of infections that occurred up to 1m prior and 1m after any decrease in IgM/IgG levels (<LLN vs ≥LLN) were analyzed. Infections in conjunction with IgM/IgG <LLN and lymphopenia and/or neutropenia on the same visit were also analyzed.
Mean IgM/IgG levels were well within reference ranges over time. Over all post-BL visits, a higher proportion of patients on ofatumumab had IgM<LLN (17.7% vs 6.6%), whilst a lower proportion had IgG<LLN (14.2% vs 22.9%) vs patients on teriflunomide. At W96, a similar trend was observed (IgM<LLN: 11.1% vs 1.9%; IgG<LLN: 2.7% vs 6.0%). Proportion of patients on ofatumumab who experienced ≥1 infection within 1m prior and until 1m after IgM<LLN was 31.1% (52/167; 2 serious) vs 51.5% (400/777) with IgM≥LLN (18 serious). Similarly, 27.6% (37/134) reported infections during a drop in IgG<LLN (3 serious) vs 50.6% (410/810) with IgG≥LLN (21 serious). The most common infection was nasopharyngitis. Overall, 1/11 patients with concurrent IgM<LLN and lymphopenia and/or neutropenia, and 7/20 patients with concurrent IgG<LLN and lymphopenia and/or neutropenia reported infections; none were serious.
Reduction in serum IgM levels was observed over time, but for the majority of patients, Ig levels remained above the lower limit of normal. No decrease in IgG levels was reported within the observation period (mean follow-up: 18m). There was no apparent association between decreased Ig levels and infections in conjunction with lymphopenia and/or neutropenia in ofatumumab-treated RMS patients.