AstraZeneca blockbuster prospect is a key test of light amyloidosis
Astrazeneca's failure to use it as one of its main potential revenue growth drivers over the next decade has led to pivotal research on light amyloidosis, a rare disease with few treatment options. Despite the setbacks, the company pointed out signs of a subgroup of patients that could provide a way forward.
AstraZeneca did not provide specific details about the results of the Phase 3 test, except that Anselamimab's medication was not statistically significant for the primary target of measuring hospital frequency and time to death for any cause. Astrazeneca said its rare disease subsidiary, Alexion, will share the results with regulators and present them at future medical conferences.
Amyloidosis is a disease in which folded proteins (called amyloid fibrils) accumulate in organs and tissues. In light amyloidosis, plasma cells in the bone marrow abnormally produce immunoglobulin light chain proteins. The accumulation of these abnormal proteins is particularly evident in the heart and kidneys. Heart failure is the most common cause of death in patients with this disease.
The standard treatment for light amyloidosis is chemotherapy cyclophosphamide as well as the cancer drug velcade and the steroid drug dexamethasone. The newer drug option is Darzalex Faspro, a subcutaneous injection version of the large-scale Johnson and Johnson multiple myeloma Darzalex. In 2021, the antibody has expanded its approval to include newly diagnosed light amyloidosis.
Anselamimab is a monoclonal antibody designed to bind to misfolded amyloid fibrils to reduce or eliminate the deposition of these proteins in tissues and organs. The drug is designed to specifically bind targets of misfolded amyloid, accounting for the original free light chain. Anselamimab's Phase 3 program consists of two placebo-controlled Phase 3 studies, each testing the drug at different stages of light amyloidosis. These studies are evaluating Anselamimab and standard treatments for the disease.
Overall, a total of 406 patients from 19 countries were recruited. Participants were randomly assigned to receive study medication or once a week as a placebo for intravenous infusion during the first four weeks and then every two weeks until week 50. AstraZeneca said about 80% of participants received J&J medication as part of the treatment. Participants who completed the study had the option to participate in an open-label extended study that evaluated Anselamimab as well as treatment at a maximum of 24 months of nursing level.
In Astrazeneca's announcement of Phase III readings, Dr. Ashutosh Wechalekar, a consultant to the NHS Foundation Foundation at University College London, professor of medicine and hematology at University College London, and lead investigator in the Phase III course, highlighted subgroup results-not describing or defining subgroups.
“Although this study does not meet the primary endpoints of the overall patient population, the results from the predefined subgroup suggest that by targeting and clearing amyloid deposits, Anselamimab can address the main causes of organ damage and dysfunction in these patients,” Wechalekar said. “The potential to expand survival and reduce cardiovascular hospitalization will represent practice changes in this patient group.”
AstraZeneca said the results showed that Anserramob was well tolerated, with most events balancing between the Aesaimabu treatment arm and the placebo arm. No details about these events were disclosed. The company said an evaluation of the complete trial results is underway to further characterize the efficacy and safety of Anselamimab.
Light amyloidosis has been shown to be challenging for drug developers. Prothena announced in May that its antibody drug Birtamimab did not meet its primary target of phase 3 testing. Birtamimab has previously failed in the interim study, but has recovered and returned to Phase 3 based on improvements in the subgroup of high-risk patients. After the latest clinical trial failed, Dublin's Prothena stopped the program and began a company restructuring. Other companies that fell due to light amyloidosis drugs include Takeda Pharmaceutical and GSK.
In a 2024 investor speech on Alexander’s Rare Disease portfolio and pipeline, AstraZeneca listed Anselamimab as one of three drug candidates with the potential to contribute $1 billion to $3 billion in potential peak revenue.
Anselamimab (formerly known as CAEL-101) comes with Astrazeneca's 2021 acquisition of Alexion Pharmaceuticals. Alexion worked with Caelum Biosciences, the original developer of the drug in 2019. The alliance grants Alexion a minority stake in Biotech and has the option to acquire the remaining shares. AstraZeneca exercised this option, paying about $150 million. Another $350 million is related to achieving milestones.
Photo: Christopher Furlong, Getty Images
