Alexion and Caelum Biosciences Announce Start of Phase 3 Studies of CAEL-101 in AL Amyloidosis

- Phase 2 study met primary objective, supporting initiation of two parallel Phase 3 studies that will enroll ~370 AL amyloidosis patients -

- Positive long-term Phase 1a/1b data presented at the International Symposium on Amyloidosis (ISA) 2020 demonstrate prolonged overall survival (78% at 37 months) and durable organ response -

BOSTON & BORDENTOWN, NJ, USA I September 14, 2020 IAlexion Pharmaceuticals, Inc. (NASDAQ:ALXN) and Caelum Biosciences today announced the initiation of the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101, a first-in-class amyloid fibril targeted therapy, in combination with standard-of-care (SoC) therapy in AL amyloidosis. The CARES clinical program includes two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease and one in patients with Mayo stage IIIb disease – and will collectively enroll approximately 370 patients globally. Enrollment is underway in both studies. The primary objective of the clinical program is to assess overall survival.

“In AL amyloidosis, misfolded amyloid proteins can build up in many organs throughout the body, including the heart and kidneys, causing significant damage to these organs and impairing their function. While current treatments address the bone marrow disorder that creates the misfolded amyloid proteins, there are no approved therapies for the significant organ damage the disease causes,” said John Orloff, M.D., Executive Vice President and Head of Research and Development at Alexion. “CAEL-101 has the potential to be the first treatment to target and remove the amyloid deposits from these organs. Data from Phase 1 studies suggest that this treatment approach may improve organ function and long-term survival. We look forward to investigating this further in the Phase 3 clinical program.”

“AL amyloidosis is particularly devastating when it affects the heart, with median survival in these patients of less than one year following diagnosis,” said Michael Spector, President and Chief Executive Officer of Caelum. “Long-term survival data from AL amyloidosis patients treated with CAEL-101 in the Phase 1a/1b study showed that 78 percent were still alive after a median follow-up time of more than three years. We recognize the urgent need for new treatments that address the organ damage caused by AL amyloidosis and are working together with the AL amyloidosis community and Alexion to advance the Phase 3 clinical program as quickly as possible.”

About the CARES Phase 3 Clinical Program

The CARES clinical program consists of two parallel double-blind, randomized, event-driven global Phase 3 studies, which are evaluating the efficacy and safety of CAEL-101 in AL amyloidosis patients who are newly diagnosed and naïve to standard of care (SoC) treatment (cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy). One study is enrolling approximately 260 patients with Mayo stage IIIa disease and one study is enrolling approximately 110 patients with Mayo stage IIIb disease. The studies will be conducted at approximately 70 sites across North America, the United Kingdom, Europe, Israel, Japan, and Australia.

In each study, participants are being randomized in a 2:1 ratio to receive either CAEL-101 plus SoC or placebo plus SoC once weekly for four weeks. This will be followed by a maintenance dose administered every two weeks until the last patient enrolled completes at least 50 weeks of treatment. Patients will continue follow-up visits every 12 weeks.

The primary study objectives are overall survival and the safety and tolerability of CAEL-101. Key secondary objectives will assess functional improvement in the six-minute walk test (6MWT), quality of life measures (Kansas City Cardiomyopathy Questionnaire Overall Score & Short Form 36 version 2 Physical Component Score) and cardiac improvement (Global Longitudinal Strain, or GLS).

Phase 2 Study Results

The Phase 2 open-label dose escalation study was conducted to investigate higher doses of CAEL-101 than had been evaluated in Phase 1 studies with a primary objective to identify the best dose to advance into Phase 3 development. The study evaluated the safety and tolerability of CAEL-101 in 13 AL amyloidosis patients at three study sites who received up to 1000 mg/m2 of CAEL-101 (two times the Phase 1 dose) administered in combination with SoC treatment. The study met its primary objectives, supporting the safety and tolerability of CAEL-101 and the selection of the 1000 mg/m2 dose for the Phase 3 study.

Phase 1a/1b Long-Term Follow-Up Results Presented at ISA 2020

As previously reported, the Phase 1a/1b study of CAEL-101 was the first clinical trial to demonstrate improvement in cardiac function via GLS after treatment with an amyloid fibril targeted therapy in AL amyloidosis patients with amyloid cardiac involvement. New long-term follow-up data from the Phase 1a/1b study will be presented at the virtual International Symposium on Amyloidosis (ISA), September 14 to 18, 2020, in the poster titled, “Long term follow-up of patients with AL amyloidosis treated on a phase 1 study of Anti-Amyloid Monoclonal Antibody CAEL-101” (Abstract #342, Divaya Bhutani, M.D., et. al, Columbia University Medical Center). These data demonstrate 78 percent survival (15/19) at a median follow-up of more than three years (37 months) in AL amyloidosis patients treated with CAEL-101 as well as durable organ response among evaluable patients, further supporting the advancement of CAEL-101 into Phase 3 development.

About CAEL-101

CAEL-101 is a first-in-class monoclonal antibody (mAb) designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients with AL amyloidosis. The antibody is designed to bind to misfolded light chain protein and amyloid and shows binding to both kappa and lambda subtypes. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in 27 patients with relapsed and refractory AL amyloidosis who had previously not had an organ response to standard of care therapy. CAEL-101 has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicine Agency as a therapy for patients with AL amyloidosis.

About AL Amyloidosis

AL amyloidosis is a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. Misfolded immunoglobulin light chains produced by plasma cells aggregate and form fibrils that deposit in tissues and organs. This deposition can cause widespread and progressive organ damage and high mortality rates, with death most frequently occurring as a result of cardiac failure. Current standard of care includes plasma cell directed chemotherapy and autologous stem cell transplant, but these therapies do not address the organ dysfunction caused by amyloid deposition, and up to 80 percent of patients are ineligible for transplant.

AL amyloidosis is a rare disease but is the most common form of amyloidosis. There are approximately 22,000 patients across the United States, France, Germany, Italy, Spain and the United Kingdom. AL amyloidosis has a one-year mortality rate of 47 percent, 76 percent of which is caused by cardiac amyloidosis.

About Alexion

Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. As a leader in rare diseases for more than 25 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D) as well as the first and only approved Factor Xa inhibitor reversal agent. In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, metabolic disorders and cardiology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at:


About Caelum Biosciences

Caelum Biosciences, Inc. (“Caelum”) is a clinical-stage biotechnology company developing treatments for rare and life-threatening diseases. Caelum’s lead asset, CAEL-101, is a novel antibody for the treatment of patients with amyloid light chain (“AL”) amyloidosis. In 2019, Caelum entered a collaboration agreement with Alexion under which Alexion acquired a minority equity interest in Caelum and an exclusive option to acquire the remaining equity in the company based on Phase 3 CAEL-101 data. Caelum was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit

SOURCE: Caelum Biosciences

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