Second March Readout Not the Charm for AnaptysBio as Imsidolimab Misses Again

AnaptysBio announced that its drug candidate imsidolimab did not demonstrate efficacy in Phase II clinical trials in the treatment of moderate-to-severe acne.

The ACORN trial enrolled 123 moderate-to-severe acne patients in the U.S. who were washed out of prior therapy. The patients were treated with a 400mg subcutaneous dose of imsidolimab on Day 1, followed by monthly 200mg doses at weeks four and eight of the trial. 

The primary endpoint of the ACORN trial was a mean change in facial inflammatory lesion count after treatment relative to baseline. However, in the latest data shared by AnaptysBio, imsidolimab failed to demonstrate efficacy over placebo on both primary and secondary endpoints. 

This setback may be all too familiar to AnaptysBio, which reported in March 2021 that imsidolimab failed to reach efficacy against a placebo in clinical trials in the treatment of moderate-to-severe palmoplantar pustulosis (PPP), a rare inflammatory disorder that results in crops of sterile pustules on the hands and feet. 

Despite setbacks, clinical development of imsidolimab is still being advanced for the treatment of generalized pustular psoriasis (GPP), a life-threatening systemic inflammatory disease, and moderate-to-severe hidradenitis suppurativa, a condition that causes painful lumps under the skin.

Data shared in October 2021 by AnaptysBio shows promising results using imsidolimab in the treatment of GPP, which currently has no approved treatments or therapies. Eight patients were enrolled in the GALLOP Phase II trial who had active ongoing GPP disease and at least 10% of their body surface area covered by active pustules and erythema. Patients were treated with a 750mg intravenous induction dose of imsidolimab on Day 1 of the trial, followed by monthly 100mg subcutaneous doses. 

Results showed that 75% of patients treated demonstrated rapid and sustained efficacy, achieving the primary endpoint. Additionally, early erythema reduction with pustules was 60% at week one, which improved to a 94% reduction at week four of the trial. 

Imsidolimab received orphan drug designation in July 2020 from the U.S. Food and Drug Administration for the treatment of patients with GPP. The therapeutic is an antibody that inhibits the function of the interleukin-36-receptor (IL-36R). 

IL-36 is important in bridging innate and adaptive immune responses, and in patients with certain dermatological and inflammatory diseases, there is a disturbed balance between pro-inflammatory and anti-inflammatory branches, leading to tissue inflammation. By inhibiting the function of IL-36R, imsidolimab dampens disease response by blocking the receptor for IL-36.

The future remains unclear for imsidolimab in the treatment of inflammatory skin conditions. AnaptsyBio has previously expanded the therapeutic’s program into four dermatological inflammatory Phase II clinical trials, including conditions such as EGFRi-mediated skin toxicities and ichthyosis. Data from Phase II and III trials evaluating imsidolimab in GPP and moderate-to-severe hidradenitis suppurativa are anticipated in 2022.

Beyond imsidolimab, AnaptsyBio is advancing its candidate rosnilimab in the treatment of alopecia areata, a condition in which the immune system attacks hair follicles, causing hair loss. Enrollment is ongoing in Phase II trials, and results from Phase I trials are anticipated in 2022.