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Abstract Details

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
Autoimmune Neurology
S43 - Immunotherapies and Drug Trials in Autoimmune Neurological Disorders (3:30 PM-3:41 PM)
001

Rozanolixizumab is an SC anti-FcRn monoclonal antibody designed to remove pathogenic IgG autoantibodies in autoimmune diseases.

Report results from a Phase 2a study of rozanolixizumab in patients with GMG (NCT03052751).

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.

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.

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.

Authors/Disclosures
Vera Bril, MD (Toronto General Hospital)
PRESENTER
Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Grifols. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Powell Mansfield. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta (now J&J). Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NovoNordisk. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Bril has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Akcea. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL. Dr. Bril has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Bril has received research support from UCB. The institution of Dr. Bril has received research support from Argenx. The institution of Dr. Bril has received research support from Momenta (now J&J). The institution of Dr. Bril has received research support from Immunovant. The institution of Dr. Bril has received research support from Alexion. The institution of Dr. Bril has received research support from Takeda. The institution of Dr. Bril has received research support from Grifols. The institution of Dr. Bril has received research support from CSL. The institution of Dr. Bril has received research support from Octapharma. The institution of Dr. Bril has received research support from Akcea. The institution of Dr. Bril has received research support from Ionis. The institution of Dr. Bril has received research support from Viela Bio (now Horizon). Dr. Bril has received intellectual property interests from a discovery or technology relating to health care.
Michael G. Benatar, MBChB, DPhil, FAAN (University of Miami) Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Benatar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Benatar has received personal compensation in the range of $0-$499 for serving as a Consultant for Annexon. Dr. Benatar has received personal compensation in the range of $0-$499 for serving as a Consultant for UniQure. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cartesian. Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Benatar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CorEvitas. Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Canopy. Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alaunos. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prilenia. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Woolsey. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Benatar has received intellectual property interests from a discovery or technology relating to health care.
Melissa Brock (SCHWARZ BIOSCIENCES, Inc.) No disclosure on file
Bernhard Greve, MD (UCB Biosciences GmbH) Dr. Greve has received personal compensation for serving as an employee of UCB Biosciences. Dr. Greve has stock in UCB Biosciences.
Peter Kiessling No disclosure on file
Franz Woltering No disclosure on file
Peter Y. Van Den Bergh, MD, PhD, FAAN (Cliniques Universitaires St Luc, Service de Neurologie) Dr. Van den Bergh has nothing to disclose.