P2033 - Safety and Efficacy of Long-Term Treatment With Lirentelimab, A Monoclonal Antibody Against Siglec-8, in Patients With Eosinophilic Gastritis and/or Duodenitis

Joseph A. Murray, MD¹, Kathryn Peterson, MD, MSCI², Mirna Chehade, MD, MPH³, Gary Falk, MD, MS, FACG⁴, NIrmala Gonsalves, MD⁵, Robert M. Genta, MD, FACG⁶, John Leung, MD⁷, Paneez Khoury, MD⁸, Amy Klion, MD⁸, Sabine Hazan, MD⁹, Michael Vaezi, MD¹⁰, Adam Bledsoe, MD¹, Sandy Durrani, MD¹¹, Chao Wang, PhD¹², Camilla Shaw, BSN, RN¹³, Alan Chang, BS¹³, Bhupinder Singh, MD¹³, Amol P. Kamboj, MD¹³, Henrik Rasmussen, MD, PhD¹³, Marc Rothenberg, MD, PhD¹⁴, Ikuo Hirano, MD⁵, Evan S. Dellon, MD, MPH, FACG^15
1Mayo Clinic, Rochester, MN; ²University of Utah School of Medicine, Salt Lake City, UT; ³Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY; ⁴University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; ⁵Northwestern University Feinberg School of Medicine, Chicago, IL; ⁶Inform Diagnostics, Irving, TX; ⁷Tufts University Medical Center, Boston, MA; ⁸National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethedsa, MD; ⁹Ventura Clinical Trials, Ventura, CA; ¹⁰Vanderbilt University Medical Center, Nashville, TN; ¹¹Cincinnati Children's Hospital Medical Center, Cincinnati, OH; ¹²Pharma Data Associates, Piscataway, NJ; ¹³Allakos, Inc., Redwood City, CA; ¹⁴Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH; ¹⁵University of North Carolina School of Medicine, Chapel Hill, NC

Introduction: Eosinophilic gastritis (EG) and/or duodenitis (EoD) are characterized by chronic gastrointestinal symptoms and accumulation and activation of eosinophils and mast cells in the stomach and/or duodenum. Lirentelimab (AK002), an antibody against siglec-8, depletes eosinophils and inhibits mast cells. In a 16-week randomized, double-blind phase 2 study of patients with moderate–severe EG and/or EoD (ENIGMA), lirentelimab significantly reduced gastrointestinal eosinophils and patient-reported total symptom scores (TSS) compared with placebo. To evaluate the long-term safety and efficacy of lirentelimab, we conducted an open-label extension (OLE) study, and present data by disease type (EG±EoD vs EoD without EG) through week 94.

Methods: Fifty-eight of 59 eligible patients, who received 4 monthly infusions of lirentelimab or placebo during the ENIGMA study, entered the OLE study and received up to 26 monthly doses of lirentelimab (0.3 or 1 mg/kg escalating to 3 mg/kg). Abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating, and diarrhea were assessed using a daily electronic patient-reported outcome questionnaire to generate weekly TSS. Patients underwent upper endoscopy with biopsy at screening, week 14 of ENIGMA, and 2 timepoints during the OLE study. Histopathologic analyses were performed by a blinded central pathologist; EG and EoD were defined as ≥30 eos/hpf in ≥5 gastric hpfs and ≥30 eos/hpf in ≥3 duodenal hpfs, respectively.

Results: As of March 2021, 13 patients with EG±EoD and 12 patients with EoD without EG received 94 weeks of lirentelimab (ENIGMA+OLE). At week 94, mean TSS was reduced by 70% in patients with EG±EoD and 81% in patients EoD without EG compared with baseline (Table). TSS decreased significantly from baseline through week 94 regardless of EG±EoD or EoD without EG (Figure). Gastro-duodenal eosinophil counts were significantly reduced. There were no drug-related serious adverse events. The most common adverse events were mild–moderate infusion-related reactions, mostly during the first infusion.

Discussion: In an OLE study, patients with EG±EoD or EoD without EG receiving lirentelimab for up to 94 weeks had sustained and similar reductions in TSS and eosinophil counts in gastric and duodenal biopsies—patients benefited regardless of whether the stomach was involved. Long-term treatment with lirentelimab (AK002) was well tolerated and holds promise for patients with EG and/or EoD.




Disclosures:


Joseph A. Murray, MD¹, Kathryn Peterson, MD, MSCI², Mirna Chehade, MD, MPH³, Gary Falk, MD, MS, FACG⁴, NIrmala Gonsalves, MD⁵, Robert M. Genta, MD, FACG⁶, John Leung, MD⁷, Paneez Khoury, MD⁸, Amy Klion, MD⁸, Sabine Hazan, MD⁹, Michael Vaezi, MD¹⁰, Adam Bledsoe, MD¹, Sandy Durrani, MD¹¹, Chao Wang, PhD¹², Camilla Shaw, BSN, RN¹³, Alan Chang, BS¹³, Bhupinder Singh, MD¹³, Amol P. Kamboj, MD¹³, Henrik Rasmussen, MD, PhD¹³, Marc Rothenberg, MD, PhD¹⁴, Ikuo Hirano, MD⁵, Evan S. Dellon, MD, MPH, FACG¹⁵. P2033 - Safety and Efficacy of Long-Term Treatment With Lirentelimab, A Monoclonal Antibody Against Siglec-8, in Patients With Eosinophilic Gastritis and/or Duodenitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.