AnaptysBio, Inc. announced that top-line data from its Phase 2 clinical trial of imsidolimab for the treatment of moderate-to-severe acne, also known as the ACORN trial, did not demonstrate efficacy over placebo on primary or secondary endpoints. AnaptysBio continues to advance three wholly-owned pipeline programs through clinical development. While clinical development is being discontinued in acne, imsidolimab demonstrated efficacy and safety in the GALLOP Phase 2 trial in generalized pustular psoriasis (GPP) and enrollment of the GEMINI-1 GPP Phase 3 trial is ongoing and top-line data from the imsidolimab HARP Phase 2 trial in moderate-to-severe hidradenitis suppurativa is anticipated during the second half of 2022.

Beyond imsidolimab, enrollment is ongoing in the AZURE Phase 2 trial of rosnilimab, a PD-1 agonist antibody, in moderate-to-severe alopecia areata and healthy volunteer Phase 1 top-line data for ANB032, a BTLA modulator antibody, is anticipated in the second quarter of 2022. Top-line data from the ACORN trial are as follows: Mean baseline facial inflammatory lesion counts for the imsidolimab high dose arm, the imsidolimab low dose arm and placebo arm were 30, 29 and 27, respectively. Each arm had an average baseline facial investigator global assessment (IGA) score of 3.1. Patients were on average 20 years of age and 65% were female.

Imsidolimab was generally safe, well tolerated and no treatment-related severe or serious adverse events were observed (Table 1). Treatment-emergent adverse events (TEAEs) in both imsidolimab arms resolved without leading to treatment discontinuation and TEAE timing did not correlate with dosing. The most common TEAEs observed across imsidolimab and placebo dosed patients were COVID diagnoses and upper respiratory tract infections (URTI), which were deemed unrelated to treatment.

Three patients were diagnosed with treatment-unrelated COVID and three patients reported treatment-unrelated URTIs in the imsidolimab high dose arm, while one instance of each were reported in the imsidolimab low dose arm. The placebo arm reported five patients with COVID diagnoses, of which one also reported a URTI, which were all treatment-unrelated. Severe TEAEs included one patient with treatment-unrelated URTI in the imsidolimab high dose arm, one patient with treatment-unrelated oropharyngeal pain and associated fatigue in the imsidolimab low dose arm and one patient in the placebo arm with treatment-unrelated severe COVID diagnosis.

Fallopian tube cyst and associated pelvic pain were reported as treatment-unrelated serious TEAEs in one imsidolimab high dose patient. One placebo-dosed patient discontinued treatment due to proteinuria. The primary endpoint of facial inflammatory lesion count change from baseline at week 12 was -6.8 (-27%) for the imsidolimab high dose arm, -7.4 (-21%) for the imsidolimab low dose arm and -9.6 (-38%) for the placebo arm.

Facial IGA of clear (zero) or almost clear (1) with at least a 2-point decrease from baseline, a secondary endpoint, was achieved at week 12 by 12% of patients in the imsidolimab high dose arm, 0% of the patients in the imsidolimab low dose arm and 14% of patients in the placebo arm. ACORN Phase 2 Trial Design: One hundred and twenty-three moderate-to-severe acne patients were enrolled in this trial at 15 sites located within the USA. Patients were washed out of prior therapy and no concomitant therapy was permitted during the trial.

Key inclusion criteria included age between 12 and 45 years, clinically confirmed ongoing moderate-to-severe acne with minimum facial IGA score of at least 3 (moderate), at least 20 inflammatory facial lesions and no more than 5 nodules present upon enrollment. Patients in the imsidolimab high dose arm were treated with a 400mg subcutaneous induction dose at Day 1, followed by monthly 200mg subcutaneous doses at weeks 4 and 8, while the imsidolimab low dose arm was treated with a 200mg subcutaneous induction dose and monthly 100mg subcutaneous doses. The primary endpoint of this trial was mean change in facial inflammatory lesion count at week 12 relative to baseline.

Baseline clinical assessments were conducted for each patient at screening and on Day 1 prior to imsidolimab dosing. Missing data was modeled using mixed model for repeated measures (MMRM) methodology.