Biogen Inc. Announces Positive Phase 2 Results for Litifilimab in Cutaneous Lupus Erythematosus

Biogen Inc. announced positive results from the Phase 2 part of the AMETHYST Phase 2/3 study (Part A) of litifilimab in people living with cutaneous lupus erythematosus (CLE). Litifilimab is the first humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2), which has the potential to become the first innovative therapy approved for CLE in 70 years. Part A of AMETHYST evaluated the efficacy and safety of litifilimab through week 24, with reductions in skin disease activity reported across several measures.

Results are consistent with the earlier positive Phase 2 LILAC study reported in The New England Journal of Medicine. Phase 2 results from LILAC and AMETHYST supported litifilimab?s recently granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation. CLE is a complex, heterogenous disease that affects millions of people around the world.

there are no targeted therapies approved to treat CLE. AMETHYST is an ongoing seamless two-part, multicenter, double-blind, placebo controlled, randomized study to evaluate the efficacy and safety of litifilimab compared to placebo in participants with a variety of CLE severities. Participants are randomized to receive subcutaneous treatment with litifilimab with standard of care (SoC) or placebo every four weeks in addition to SoC.

All participants will receive litifilimab during the 28-week extended treatment period from Weeks 24 to 48. Results reported here are from the double-blind, placebo-controlled Phase 2 (Part A) portion of AMETHYST, Week 0 to 24. In the study, 74% of participants are women and 33% are non-white.

This demographic distribution is consistent with the epidemiology of CLE which disproportionately affects women and diverse ethno-racial groups. The Phase 3 part of the study is ongoing and results remain blinded. AMETHYST Part A met its primary endpoint with litifilimab demonstrating a statistically significant 11.8% higher reduction in disease activity in people living with CLE (95% confidence interval [CI]: 1.39, 22.27; p < 0.05) as measured by the Cutaneous Lupus Activity Investigators?

Global Assessment Revised (CLA-IGA-R) erythema score of 0-1 (clear/almost clear) at Week 16, compared to placebo (14.7% vs. 2.9%). Secondary endpoints, including the following, were not adjusted for multiplicity in Part A and therefore statistical significance cannot be demonstrated.

Litifilimab was associated with rapid and continued improvement in skin disease activity with separation from placebo observed as early as Week 4 (19.3% vs. 5.5%; ?= 13.8; CI: 1.19, 26.46), as measured by Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity-50 (CLASI-50) response through Week 24 (40.8% vs. 21%; ?= 19.8; CI: 1.46, 38.15).

More participants receiving litifilimab achieved a response compared to placebo (21.7% vs 5.8%), as measured by CLASI-70 at Week 24. CLASI-50 and CLASI-70 responses are defined as 50% and 70% improvements from baseline in CLASI-A score, respectively. Additionally, 1 in 6 participants receiving litifilimab achieved a CLASI 0-3 score, defined as no or minimal disease activity, compared to placebo at Week 24 (16.3% vs 0%; ?= 16.3; CI: 7.07, 25.62).

Litifilimab was generally well tolerated in Part A of the AMETHYST study and tolerability was consistent with the safety profile established in completed studies, including the Phase 2 LILAC study. Adverse events (AEs) were reported in 74.6% (44/59) and 64.7% (22/34) of participants receiving litifilimab and placebo, respectively, in the 24-week period. Most AEs were mild to moderate in severity.

Serious adverse events occurred in 6.8% (4/59) and 2.9% (1/34) of participants receiving litifilimab and placebo, respectively. AMETHYST is a two-part, Phase 2/3 multicenter, double-blind, placebo controlled, randomized study to evaluate the efficacy and safety of litifilimab compared to placebo. The study aims to assess the efficacy of litifilimab in participants with active subacute cutaneous lupus erythematosus (SCLE) and/or chronic cutaneous lupus erythematosus (CCLE) who are refractory or intolerant to antimalarial therapy.

The Phase 2 and Phase 3 parts of the study will each be 52 weeks in duration. Participants will be randomized to receive subcutaneous treatment with litifilimab or placebo every four weeks for 20 weeks with an additional dose at Week 2. All participants will receive litifilimab during the 28-week extended treatment period from Weeks 24 to 48. Litifilimab (known as BIIB059), discovered and developed in-house by Biogen scientists, is a humanized IgG1 monoclonal antibody (mAb) targeting BDCA2 and is being investigated for the potential treatment of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

BDCA2 is a receptor that is predominantly expressed on a subset of human immune cells called Plasmacytoid Dendritic Cells (pDCs). Binding of litifilimab to BDCA2 has been shown to reduce production of pro-inflammatory molecules by pDCs, including type-I interferon (IFN-I) as well as other cytokines and chemokines. These pro-inflammatory mediators are thought to play a major role in the pathogenesis of systemic and cutaneous lupus.

Litifilimab is an investigational therapeutic candidate that has not yet been approved by any regulatory authority and its safety and effectiveness have not been established. CLE, a type of lupus, is a serious chronic autoimmune skin disease that can occur with or without systemic manifestations; people with CLE frequently experience symptoms including rash, pain, itch and photosensitivity as well as skin damage that may worsen over time and can include irreversible scarring, alopecia and dyspigmentation that can be disfiguring and substantially impact quality of life. Currently, there are no approved targeted therapies for CLE and the last drug was approved in the 1950s.