A drug that AstraZeneca singled out as one of its key potential revenue growth drivers in the next decade has failed a pivotal study in light chain amyloidosis, a rare disease with few treatment options. Despite the setback, the company points to encouraging signs in a subgroup of patients that could offer a path forward.
AstraZeneca provided no specific details about the results of the Phase 3 test other than to say that the drug, anselamimab, did not reach statistical significance on the main goal measuring the frequency of hospitalizations and the time to death from any cause. AstraZeneca said Alexion, its rare diseases subsidiary, will share the results with regulatory authorities and present them at a future medical meeting.
Amyloidosis is a disorder in which abnormally folded proteins, called amyloid fibrils, build up in organs and tissue. In light chain amyloidosis, plasma cells in the bone marrow abnormally produce immunoglobulin light chain proteins. Buildup of these abnormal proteins is particularly pronounced in the heart and kidneys. Cardiac failure is the most common cause of death for patients with this disease.
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Standard treatment for light chain amyloidosis is the chemotherapy cyclophosphamide alongside the cancer drug Velcade and the steroid medication dexamethasone. A newer drug option is Darzalex Faspro, a subcutaneously injectable version of the blockbuster Johnson & Johnson multiple myeloma drug Darzalex. In 2021, this antibody expanded its approval to include newly diagnosed light chain amyloidosis.
Anselamimab is a monoclonal antibody designed to bind to misfolded amyloid fibrils to reduce or eliminate deposits of these proteins in tissues and organs. This drug is intended to specifically bind to targets on misfolded amyloid, sparing native free light chains. The Phase 3 program for anselamimab consists of two placebo-controlled Phase 3 studies, each testing the drug in a different stage of light chain amyloidosis. These studies are assessing anselamimab alongside standard treatment for the disease.
In total, the studies have enrolled 406 patients from 19 countries. Participants were randomly assigned to receive the study drug or a placebo administered as an intravenous infusion once weekly for the first four weeks and then every two weeks until week 50. Darzalex was permitted but not required as part of the standard regimen. AstraZeneca said about 80% of participants received the J&J drug as part of their treatment. Participants who completed the study had the option to participate in an open-label extension study evaluating anselamimab plus standard of care treatment for up to 24 months.
In AstraZeneca’s announcement of the Phase 3 readout, Dr. Ashutosh Wechalekar, consultant haematologist at University College London Hospitals NHS Foundation Trust, professor of medicine and Haematology at University College London, and lead principal investigator of the Phase 3 program, highlighted the subgroup results — without describing or defining the subgroup.
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“While the study did not meet the primary endpoint in the overall patient population, results from a pre-defined subgroup suggest that anselamimab, by targeting and clearing amyloid deposits, may address a leading cause of organ damage and functional impairment in these patients,” Wechalekar said. “The potential to extend survival and reduce cardiovascular hospitalizations would represent a practice-changing advancement for this patient group.”
AstraZeneca said the results show anselamimab was well tolerated, with the majority of events balanced between the anselamimab treatment arm and the placebo arm. No details about those events were disclosed. The company said evaluation of the full trial results is ongoing to further characterize the efficacy and safety of anselamimab.
Light chain amyloidosis has proven challenging for drug developers. In May, Prothena announced its antibody drug birtamimab did not meet the main goal of its Phase 3 test. Birtamimab had previously failed a mid-stage study, but was revived and advanced to Phase 3 based on improvement observed in a subgroup of high-risk patients. Following the latest clinical trial failure, Dublin-based Prothena discontinued the program and commenced a corporate restructuring. Other companies that have fallen short with light chain amyloidosis drugs include Takeda Pharmaceutical and GSK.
In a 2024 investor presentation about Alexion’s rare disease portfolio and pipeline, AstraZeneca listed anselamimab as one of three drug candidates with the potential to contribute toward $1 billion to $3 billion in potential peak year revenue.
Anselamimab, formerly known as CAEL-101, came with AstraZeneca’s 2021 acquisition of Alexion Pharmaceuticals. Alexion had partnered with the drug’s initial developer, Caelum Biosciences, in 2019. That alliance gave Alexion a minority stake in the biotech and the option to acquire the rest of the shares it did not already own. AstraZeneca exercised that option in 2021, paying about $150 million. Another $350 million is tied to the achievement of milestones.
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