Amgen has shed light on its phase 2 lupus win, revealing that its monoclonal antibody daxdilimab was tied to a 6-point reduction in disease severity at the lower dose.
The pharma evaluated two doses of the ILT7-targeting IgG1 monoclonal antibody in a phase 2 study of 72 patients with discoid lupus, an autoimmune condition marked by mostly painless sores on the skin. Amgen disclosed in its earnings results back in February that the trial had hit its primary endpoint by significantly reducing disease severity at Week 24.
In an abstract published this morning, the company set out the data behind this win. Interestingly, the lower dose of daxdilimab performed slightly better when it came the key goal of reducing the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) score.
Specifically, the low dose was tied to a 6-point drop against placebo, while the higher dose was tied to a 5.7-point drop. A 6-point reduction is equivalent to a 50% reduction in lupus disease area and severity, which experts consider to be a meaningful improvement in patients’ quality of life.
Both doses of daxdilimab met the primary and secondary endpoints, according to the abstract, which was published alongside a presentation by Amgen at the European Academy of Dermatology and Venereology Congress in Milan.
Those secondary endpoints included the proportion of patients achieving a 50% or greater reduction in CLASI-A score, as well as the proportion achieving a score of 0 or 1 on a 5-point clinician-reported severity scale at Week 24.
On the former endpoint, Amgen disclosed that 61.7% and 62.1%, respectively, of patients on the low and high doses reached the 50% reduction marker, compared to 23.7% in the placebo cohort. When it came to getting down to 1 point or below on the severity scale, this was achieved by 60.3% and 51.6% on the respective daxdilimab cohorts, and 8.9% among those on placebo.
Daxdilimab was well tolerated, according to the abstract, with no serious adverse events or death reported. One patient in the high-dose cohort discontinued the study due to joint pain called arthralgia, which the study investigator considered was related to treatment. That patient was referred to a rheumatologist and his treatment was discontinued.
Daxdilimab is designed to target immunoglobulin-like transcript 7 in order to reduce the number of rare immune cells called plasmacytoid dendritic cells, which produce inflammatory molecules called interferons.
Last month, Amgen said it was already “taking steps” to take daxdilimab, which the pharma acquired from Horizon Therapeutics in 2023, into a registrational phase of development.
Amgen has also been evaluating the monoclonal antibody for dermatomyositis, but the company said back in February that a phase 2 study for this rare inflammatory disease had too small a sample size to determine efficacy.
Daxdilimab’s success in discoid lupus follows the antibody’s earlier failure in the more common systemic lupus erythematosus. In a 2023 phase 2 trial run by Horizon, the molecule failed to beat placebo at improving disease activity. That disappointment came at the same time Amgen’s $27.8 billion buyout of Horizon was on the rocks, with the U.S. Federal Trade Commission suing to block the move before the deal finally went through later in the year.
That same summer, Amgen dropped its own two midstage systemic lupus programs for futility, leaving its lupus pipeline barren.
