Amgen’s bad luck in lupus may finally be coming to an end. Daxdilimab, a monoclonal antibody acquired from Horizon Therapeutics in 2023, hit the primary endpoint in a phase 2 trial for discoid lupus erythematosus.
Daxdilimab significantly reduced disease severity in 72 patients with discoid lupus, an autoimmune condition marked by mostly painless sores on the skin. The phase 2 study is coded as “terminated” on ClinicalTrials.gov because recruitment was stopped early, an Amgen spokesperson told Fierce Biotech, but the trial was in fact completed.
The California company shared the result during a Feb. 3 earnings call, while also touting daxdilimab’s “acceptable safety and tolerability profile.” Another phase 2 trial, in dermatomyositis, had too small a sample size to determine efficacy, Amgen added.
“Encouraged by these data, we are working to advance daxdilimab to the next phase of development in this setting,” Jay Bradner, M.D., Amgen’s executive vice president of R&D, said during the call.
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.
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.
While daxdilimab hasn’t hit the jackpot in systemic lupus, Amgen hasn’t given up on the disease—long known to be a tricky area for drug development. The drugmaker is currently trialing two of its approved medicines, bispecific T-cell engager Blincyto (blinatumomab) and monoclonal antibody Uplizna (inebilizumab), in a phase 2 systemic lupus study.
But, while daxdilimab will progress on, another Amgen antibody, bemarituzumab, is not as fortunate. The pharma has stopped the Fortitude-103 trial, a phase 1b/2 study of the candidate in first-line gastric cancer, and will no longer pursue the asset in that indication. That decision was made based on bemarituzumab’s documented struggles in the earlier Fortitude-101 and Fortitude-102 trials.
“Though overall efficacy did not meet our expectations, we observed an emerging signal of putative survival benefit in a subset of biomarker-defined patients,” Bradner said. “We expect to share these findings with the scientific community in the future.”
The company is now weighing its options for bemarituzumab moving forward, an Amgen spokesperson confirmed to Fierce Biotech.
Bradner compared the bemarituzumab decision to Amgen’s recent pullback from a $400 million autoimmune pact with Kyowa Kirin, where the partners were testing the anti-OX40 antibody rocatinlimab in an array of phase 3 trials.
“As with rocatinlimab, we took a portfolio decision to focus resources on our other late-stage programs,” Bradner said.
Amgen revealed in November that phase 1b/3 Fortitude-102 had been halted due to inadequate efficacy, and phase 3 Fortitude-101 posted middling overall survival results last September.