AnaptysBio: Phase 2 rosnilimab trial did not meet primary, secondary endpoints

AnaptysBio (ANAB) announced that investigational rosnilimab was safe and well tolerated but did not meet the primary endpoint of mean change from baseline in modified Mayo Scoreor key secondary endpoints of clinical response and clinical remission at Week 12 in the global Phase 2 trial for moderate-to-severe ulcerative colitis. Placebo rates in the trial were within expected historical ranges. Given these results, this UC trial will be discontinued, resulting in at least $10 million in savings. The Phase 2 randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of rosnilimab in UC patients. The study enrolled 136 moderate-to-severe patients across the U.S. Western and Eastern Europe with a baseline mean mMS score of 6.7 who had an inadequate response to, loss of response or intolerance to, at least one conventional or advanced UC therapy. Approximately 50% of enrolled patients had prior experience with advanced therapies and 62% had an endoscopic score of 3, indicating severe disease activity. Patients were randomized to receive either 400mg of subcutaneous rosnilimab every four weeks, 800mg SC every two weeks, or placebo. Regardless of prior treatment, rosnilimab performed no better than placebo at Week 12, with clinical remission achieved by 7% of patients receiving rosnilimab 400mg Q4W or 800 mg Q2W, and 5% and 4% of patients achieving endoscopic remission, respectively. While preliminary data suggest an increase in remission rates between Week 12 and Week 24, Week 24 remission rates did not meet our six-month target product profile. Consistent with the RA Phase 2b study, blood biomarker data in the UC study for both rosnilimab doses showed ~90% depletion of pathogenic T cells at Week 12 with preliminary data suggesting these effects were sustained through Week 24. Likewise, for patients continuing in the treatment extension period, all of whom were reassigned to a less frequent, 400mg Q8W dose regimen, these reductions were sustained through Week 50. PD-1+ T cells were depleted in the colonic tissue at Week 12, consistent with the synovium in the RA Phase 2b study. Preliminary data show these reductions were observed equally with both induction doses, indicating the expected maximal pharmacological effect was obtained with the 400mg Q4W dose. Consistent with prior rosnilimab studies, a favorable safety and tolerability profile was observed, even at a 33% higher cumulative dose through 6 months in the 800mg Q2W cohort relative to the highest dose studied, 600mg Q2W, in the RA Phase 2b trial. The data through Week 12 show – Most adverse events were mild to moderate in severity; No treatment-related serious adverse events; No malignancies; No MACE, other than one myocardial infarction in the 800mg Q2W dose cohort in a patient with hyperthyroidism, hypertension, glucose intolerance, and with evidence of preexisting cardiovascular disease by cardiac catheterization; No serious, severe or opportunistic infections, other than a bilateral anterior uveitis by CMV in the 800mg Q2W dose cohort, diagnosed in a patient with pre-existing HIV; No AEs of liver enzyme elevations; Low incidence of injection site reactions and similar to placebo; No incidence of anaphylaxis or systemic hypersensitivity. Through Week 12, adverse events occurring in greater than5% of participants were nasopharyngitis, ulcerative colitis, dizziness and injection site erythema, and were all mild to moderate in severity. Rosnilimab was highly tolerable, with one patient discontinuing rosnilimab due to an AE. Separately, in the placebo cohort, there was one reported death and one case of uterine leiomyoma. The ongoing safety profile, including for patients through end-of-treatment at Week 50, remains consistent with the reported profile of all rosnilimab-treated patients through Week 12 as well as what was observed in the RA study. There have been no reported cases of malignancy or additional MACE.