AMETHYST trial of litifilimab making “strong progress,” Biogen says
Breakthrough-designated therapy being tested in large global CLE study
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Biogen is making “strong progress” with enrollment in the AMETHYST study, a Phase 2/3 clinical trial testing the company’s experimental therapy litifilimab (BIIB059) in people with cutaneous lupus erythematosus (CLE).
That’s according to Diana Gallagher, MD, Biogen’s senior vice president, head of clinical development, immunology, multiple sclerosis, and Alzheimer’s disease. In a written Q&A with Lupus News Today, Gallagher said Biogen expects that AMETHYST will be “one of the largest clinical studies ever conducted in CLE.”
CLE, sometimes called skin lupus, is a form of lupus that primarily affects the skin. In the U.S., there are currently no treatments approved specifically for CLE.
“CLE is distinct from other forms of lupus, affecting the skin with potential permanent scarring and disfigurement. It can have a substantial impact on the daily lives of individuals, and currently, there are no targeted treatment options available for CLE,” Gallagher said, adding that there is “a large unmet need for advanced treatments” to help manage this condition.
AMETHYST trial design and enrollment goals
The AMETHYST clinical trial (NCT05531565) is expected to enroll about 450 adults with CLE. Participants will be randomly assigned to receive litifilimab or a placebo, with the main goal of evaluating the treatment’s effect on standardized measures of skin disease severity. The study launched in 2022 and is now being conducted at nearly 300 sites worldwide, many of which are still recruiting patients.
“The global Phase 2/3 AMETHYST study is intended to evaluate the efficacy and safety of litifilimab compared to placebo in CLE,” Gallagher said. “The primary endpoint will assess the effect of litifilimab on skin disease activity, which we hope will build on the results of [a previous Phase 2 clinical trial called LILAC] where we saw significantly reduced skin disease activity in people with CLE compared to placebo.”
“We are encouraged by the positive response to date across sites and advocacy organizations (including the Lupus Research Alliance and Lupus Foundation of [America]), which highlight the potential of litifilimab to be a meaningful new therapy for patients, if approved,” Gallagher added.
The FDA’s designation of litifilimab as a Breakthrough Therapy supports Biogen’s belief in the potential for this investigative therapy to provide substantial improvements over available therapies.
Litifilimab is an antibody-based therapy administered by injection under the skin. It is designed to target a protein called BDCA2, which is expressed on inflammatory immune cells known as plasmacytoid dendritic cells. In people with CLE, “these immune cells often become overactive and release a lot of type I Interferons (IFN-Is), which are powerful chemicals used by the body to trigger inflammation, including in the skin,” Gallagher said, noting that “overproduction of IFN is one of the key drivers” of CLE.
By targeting BDCA2, litifilimab aims to reduce the production of type I IFN and other inflammatory signals from these immune cells, thereby dampening inflammation overall. The U.S. Food and Drug Administration (FDA) recently granted litifilimab breakthrough therapy designation as a potential treatment for CLE. This designation is intended to help speed the development and review of promising experimental treatments for serious conditions with unmet medical needs.
“The FDA’s designation of litifilimab as a Breakthrough Therapy supports Biogen’s belief in the potential for this investigative therapy to provide substantial improvements over available therapies,” Gallagher said.
Breakthrough designation and advocacy support
The Lupus Research Alliance has been collaborating with Biogen through its clinical affiliate, Lupus Therapeutics. Albert T. Roy, the organization’s president and CEO, said the designation “represents a critical step forward, acknowledging the seriousness and further underscoring the unmet medical need of this condition.”
The FDA’s decision to grant this designation was based in part on data from the Phase 2 LILAC clinical trial (NCT02847598), which tested various doses of litifilimab against a placebo in people with CLE. Results showed litifilimab significantly reduced scores on a measure of disease severity called the Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity score (CLASI-A) compared with placebo.
“CLASI-A is a tool used to measure the level of activity/inflammation of cutaneous lupus. It assesses things like erythema or redness, scaling (flakiness), skin thickness, ulcers in the mouth or nose and hair loss,” Gallagher said. “A higher CLASI-A score indicates more active and severe cutaneous lupus … [and] a reduction in CLASI-A means less active disease, less inflammation and general improvement. … This could mean the swelling goes down, and the skin and nails becoming less red and flaky, less patchy, with fewer or no sores in the mouth and nose, less hair loss.”
Gallagher noted that the CLASI-A improvements seen in LILAC “could mean meaningful changes that could positively impact quality of life.”
