Anti-FcRn Agent Batoclimab Meets Primary End Point in Phase 3 Study of Myasthenia Gravis

Chongbo Zhao, MD

Topline findings from a phase 3 trial (NCT05403541) assessing batoclimab (Harbour BioMed), or HBM9161, in patients with generalized myasthenia gravis (gMG) showed that the agent met its primary end point as well as key secondary end points. The therapy was found to be safe and well-tolerated, with no new safety signals identified.¹

Batoclimab is a human monoclonal antibody directed against the neonatal crystallizable fragment receptor (FcRn), with potential immunomodulating activity. In the study, the agent was assessed on the primary end point of change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score in acetylcholine receptor (AChR) antibody seropositive participants over a 12-week treatment period.

In a statement, principal investigator Chongbo Zhao, MD, professor of neurology, Huashan Hospital of Fudan University, said, "The pivotal clinical success sets a monumental milestone for the development of new drugs and further reinforces the position of FcRn antagonists in the treatment of MG through high-level evidence-based medicine. It also demonstrates the strong ability of Chinese clinical investigators to independently organize high-quality clinical studies of innovative therapeutics in rare diseases."¹

Secondary outcomes of the trial included change in Quantitative Myasthenia Gravis (QMG) score, percentage of AChRAb+ participants with at least 3-point improvement in QMG, and percentage of patients achieving MG-ADL score of 0 or 1 by week 12. The trial features 3 periods, the first of which randomly assigns participants 1:1:1 to either batoclimab 680 mg or 340 mg subcutaneously once a week or placebo.

In period 2, participants previously treated with batoclimab will be re-randomized to stay on batoclimab doses of 340 mg either once every week or once every 2 weeks or placebo. Using change in MG-ADL score, those who demonstrate a response to batoclimab during period 1 or 2 may enter the long-term extension, or period 3. To date, the study, which is still currently enrolling, has completed analysis on 132 individuals, with last individual visit on January 14, 2023.

In early 2021, the agent received breakthrough therapy certificate from the National Medical Products Administration. "This breakthrough therapy represents a significant advance in the treatment of multiple pathogenic-IgG mediated autoimmune diseases, where there remains a significant unmet medical need such as gMG indication," Jingsong Wang, founder, chairman, and chief executive officer, Harbour Biomed, said in a statement.¹

He added, “Despite the challenges posed by the COVID-19 pandemic, our commitment to developing life-changing therapies remained steadfast. The successful completion of this clinical trial is a testament to the clinical development capabilities and innovative dedication of our entire team, demonstrating the Company's exceptional ever-increasing business potential as well. We are excited to bring this much-needed therapy to patients, and we look forward to continuing to advance our pipeline of next-generation therapeutics to improve the lives of patients worldwide."

The therapeutic benefits of batoclimab were displayed in a phase 2 study (NCT0434688) published in Neurology and Therapy in 2022. In total, 30 eligible patients with gMG were enrolled, with 11, 10, and 9 patients in the batoclimab 680 mg, batoclimab 340 mg, and placebo groups, respectively. At the end of the 43-day treatment period, changes of –2.2 (±0.9), –4.7 (±0.6), and –4.4 (±1.0) on MG-ADL scores, the primary end point, were observed in the placebo, batoclimab 340 and 680 mg groups. Similar changes were observed in QMG, Myasthenia Gravis Composite, and 15-item Myasthenia Gravis Quality of Life scores in the respective groups. Notably, on day 120, all 4 scales in the placebo group had more significant improvement compared with the batoclimab groups, with total serum IgG levels reaching a plateau.²

REFERENCES
1. Harbour BioMed announces positive topline results from phase 3 trial of batoclimab for treatment of generalized myasthenia gravis. News release. Harbour BioMed. March 6, 2023. Accessed March 8, 2023. https://www.prnewswire.com/news-releases/harbour-biomed-announces-positive-topline-results-from-phase-iii-trial-of-batoclimab-for-treatment-of-generalized-myasthenia-gravis-301763029.html
2. Yan C, Duan R, Yang H, et al. Therapeutic effects of batoclimab in Chinese patients with generalized myasthenia gravis: a double-blinded, randomized, placebo-controlled phase 2 study. Neurol & Therapy. 2022;11:815-834. doi:10.1007/s40120-022-00345-9