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.