When AstraZeneca acquired Alexion earlier this year, bolstering its rare disease presence, it also acquired a $150m stake in Caelum Biosciences and its promising antibody for AL amyloidosis, CAEL-101.
Alexion and Caelum struck a deal to codevelop the rare disease therapy in 2019, with an option to purchase the remaining shares. AstraZeneca has now announced that it will exercise this option and acquire all remaining equity in Caelum for a further $150m with potential milestone payments for CAEL-101 of up to $350m.
CAEL-101 is a potential first-in-class monoclonal antibody for the treatment of light chain (AL) amyloidosis. The rare disease is caused by defective plasma cells in the bone marrow that create misfolded immunoglobulin proteins (amyloid) that accumulate in the tissues and organs of the body.
Standard treatment for AL amyloidosis is chemotherapy combined with thalidomide and/or steroids, which is effective but can kill the stem cells in the bone marrow. This can be corrected with an autologous stem cell transplant, where the patient’s own stem cells are removed before treatment and reinfused back afterwards. However, some patients are not suitable for this aggressive treatment, plus the disease can recur.
CAEL-101 binds to the misfolded amyloid proteins and eliminates them, improving organ function. CAEL-101 has been given orphan drug status in both the United States and European Union and, in June, was granted fast track designation by the FDA.
“With a median survival time of less than 18 months following diagnosis, there is an urgent need for new treatments for this devastating disease,” said Alexion CEO, Marc Dunoyer. “CAEL-101 has the potential to be the first therapy to target and remove amyloid deposits from organ tissues, improve organ function, and, ultimately, lead to longer lives for these patients.”
Around 20,000 people across the US, France, Germany, Italy, Spain and the UK live with AL amyloidosis classified as Mayo stage IIIa or IIIb disease.
The clinical programme for Caelum’s antibody is well-advanced, with two parallel phase 3 trials underway, one for patients with stage IIIa and one in stage IIIb of the disease. The primary endpoint for the CARES – Cardiac Amyloid Reaching for Extended Survival – programme is overall survival. Both studies are currently recruiting patients.