REDWOOD CITY, Calif.—Allakos, Inc., a company that has been developing antolimab (AK002) for the treatment of eosinophil and mast cell related diseases, has just reported results from a Phase 1 study evaluating the safety and efficacy of antolimab for patients with mast cell gastrointestinal disease.
The enrollment of Allakos’ Phase 2 ENIGMA study looked for patients with eosinophilic gastritis (EG) and/or eosinophilic duodenitis (EoD). Patients were identified with chronic moderate to severe gastrointestinal symptoms and elevated stomach and/or duodenal mast cell counts, without elevated eosinophils counts. These patients appeared to have a mast cell-driven condition, currently referred to as mast cell gastrointestinal disease (MGID).
The open-label, multi-dose, 6-month Phase 1 trial of antolimab consisted of seven patients with moderate to severe gastrointestinal symptoms and elevated mast cells (≥30 mast cells per hpf in at least 5hpfs in the stomach and/or ≥30 mast cells per hpf in at least 3hpfs in the duodenum) who did not have elevated eosinophils. Patients received 0.3 mg/kg of antolimab for the first dose, followed by 1.0 mg/kg the following month. After that, patients received monthly doses of 3.0 mg/kg for four additional months. Disease symptoms were assessed using a daily patient reported questionnaire measuring eight symptoms, the Total Symptom Score (TSS-8), which measures: abdominal pain, nausea, vomiting, early satiety, loss of appetite, abdominal cramping, bloating and diarrhea.
Six month treatment with antolimab resulted in a 64% mean reduction in TSS-8, compared to baseline. Five of seven (71%) patients had >50 percent reduction in TSS-8. The treatment effect of antolimab was similar to that observed with antolimab in patients with EG and/or EoD in the Phase 2 ENIGMA Study. Antolimab was generally well tolerated and no drug-related serious adverse events occurred during the study. The most common treatment emergent adverse event was infusion related reactions, all of which were mild.
Given the encouraging treatment response observed in this study, Allakos believes that MGID could represent a novel market opportunity. The company is conducting additional clinical studies to better characterize MGID and assess disease prevalence in patients with chronic functional gastrointestinal symptoms, including those with irritable bowel syndrome, functional dyspepsia and chronic gastritis.
Allakos also reported today the initiation of three clinical studies involving antolimab: a Phase 3 study in EG and/or EoD, a Phase 2/3 study in eosinophilic esophagitis (EoE) and a Phase 1 study of subcutaneously administered antolimab in healthy volunteers. The Phase 3 EG and/or EoD study and the Phase 2/3 EoE study follow the positive results from ENIGMA.
The Phase 3 trial seeks approximately 160 patients with active, biopsy-confirmed EG. Patients will be randomized 1:1 to receive either 1.0 mg/kg of antolimab for the first month followed by five doses of 3.0 mg/kg given monthly, or monthly placebo. The co-primary endpoints of the study are the proportion of patients achieving ≤ 4 eosinophils in 5hpfs in the stomach and/or ≤15 eosinophils in 3hpfs in the duodenum; and absolute change in TSS-6, measured using the daily patient-reported symptom questionnaire used in ENIGMA. The TSS-6 consists of the six most frequent and severe symptoms reported in ENIGMA (abdominal pain, nausea, bloating, early satiety, abdominal cramping and loss of appetite).
The Phase 2/3 trial plans to enroll around 300 patients with active, biopsy-confirmed EoE. Patients will be randomized 1:1:1 to receive either six antolimab doses of 1.0 mg/kg given monthly; 1.0 mg/kg of antolimab for the first month, followed by five doses of 3.0 mg/kg given monthly; or monthly placebo. The co-primary endpoints of the study are the proportion of patients achieving ≤6 eosinophils in a single hpf, and absolute change in dysphagia symptoms measured using a daily patient reported symptom questionnaire known as the Dysphagia Symptom Questionnaire.
The Phase 1 trial will evaluate the safety, pharmacokinetics and pharmacodynamics of subcutaneously administered antolimab in healthy volunteers.