Proof-of-Concept and Safety of the Anti-FcRn Antibody Rozanolixizumab in Patients with Moderate-to-Severe Generalized Myasthenia Gravis (GMG): A Phase 2a Study (S43.001)

Objective: Report results from a Phase 2a study of rozanolixizumab in patients with GMG (NCT03052751). Background: Rozanolixizumab is an SC anti-FcRn monoclonal antibody designed to remove pathogenic IgG autoantibodies in autoimmune diseases. Design/Methods: Adults (moderate-to-severe GMG) randomized 1:1 in Period-1 (Days [D] 1–29) to 3 once-weekly, 30-minute SC-infusions of rozanolixizumab 7mg/kg or placebo, and rerandomized in Period-2 (D29-43) to 3 once-weekly infusions of rozanolixizumab 7mg/kg or 4mg/kg. D44-99 were an observation period. Results: In Period-1, patients received rozanolixizumab (n=21) or placebo (n=22). At D29, LSMean change from baseline in quantitative-MG (QMG) score (primary outcome) was −1.8 and −1.2 with rozanolixizumab and placebo, respectively (LSMean-difference −0.7, p=0.221). Reductions in MG-composite (MGC, −3.1 vs −1.2, LSMean-difference −1.8, p=0.089) and MG-activities of daily living (MG-ADL, −1.8 vs −0.4, LSMean-difference −1.4, p=0.036) scores were also observed. MG-ADL responder rate (≥3-point improvement) was 47.6% with rozanolixizumab versus 13.6% with placebo (p=0.017). Improvements continued in Period-2: for patients continuing rozanolixizumab 7mg/kg, mean(SD) change from baseline scores 1-week post-final-dose (D50) were: QMG −5.08(3.64); MGC −8.5(4.6); MG-ADL −3.90(4.43); patients reallocated to rozanolixizumab also saw clinical improvements. Rapid total IgG and anti-AChR antibody titer reductions were seen, with mean reductions of ~68% in patients continuing rozanolixizumab 7mg/kg. During Period-1, 16/21 (76.2%) and 0/21 patients receiving rozanolixizumab and 16/22 (72.7%) and 2/22 (9.1%) taking placebo reported ≥1 TEAE and SAE, respectively. By D99, 36/43 (83.7%) rozanolixizumab-treated patients reported ≥1 TEAE, and 5/43 (11.6%) reported ≥1 SAE; no deaths occurred. As expected, headache was more frequent (57.1%) versus placebo (13.6%) (Period-1); all were manageable and resolved with standard therapies. Per protocol, three rozanolixizumab-treated patients with headache withdrew. Conclusions: Proof-of-concept was achieved based on clinically-meaningful improvements in MG outcomes and reductions in autoantibody titers, although difference versus placebo for the primary outcome was not statistically significant. The safety profile was consistent with other SC rozanolixizumab studies. Disclosure: Dr. Bril has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, UCB, Alnylam, Alexion, Grifols, Octapharma, Shire, Pfizer and Bionevia. Dr. Bril has received research support from CSL Behring, UCB, Alnylam, Alexion, Grifols, Octapharma, Shire, and Bionevia. Dr. Benatar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Agency for Toxic Substances and Disease Registry, Anylam Pharmaceuticals, Avexis, Biogen Inc., Denali, Journal Watch Neurology, Mitsubishi Tanabe Pharma, Morris James LLC, Muscular Dystrophy Association, National Institute of Health, NMD Pharma, Ra Pharmaceuticals, US Department of Defense, and UCB Biosciences Inc. Dr. Brock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB. Dr. Greve has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Biosciences GmbH, Germany. Dr. Greve holds stock and/or stock options in UCB Biosciences GmbH, Germany. Dr. Kiessling has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB. Dr. Woltering has nothing to disclose. Dr. Van den Bergh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam, CSL Behring, Pfizer, Genzyme. Dr. Van den Bergh has received personal compensation in an editorial capacity for Alnylam, Pfizer, CSL Behring.