anselamimab (CAEL-101) / AstraZeneca - LARVOL DELTA

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions. (PubMed, Curr Heart Fail Rep) - "The standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemotherapy for AL-CA...Recent data from ATTRibute-CM led to the approval of acoramidis, whereas patisiran received refusal based on the APOLLO-B trial. Novel CRISPR-Cas9-based drugs (i.e., NTLA-2001) hold great potential in the setting of ATTR-CA...However, the investigation of monoclonal antibodies targeting misfolded ATTR (e.g., PRX004, NI301A) or AL (e.g., birtamimab, anselamimab) has led to encouraging results. Various cutting-edge strategies are being tested for treatment of CA and may change the prognostic landscape of this condition in the next years."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders

Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Alexion Pharmaceuticals, Inc. | Phase classification: P1a/1b ➔ P1

Phase classification • Amyloidosis

New therapies to treat cardiac amyloidosis. (PubMed, Curr Opin Cardiol) - "The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

Development of Anti-Amyloid 11-1F4- CAR Phagocytes for Treatment of AL Amyloidosis (ASH 2024) - "Anselamimab (11-1F4, CAEL-101) is an AL amyloid fibril specific monoclonal antibody currently being tested in phase 3 clinical trials, which triggers amyloid clearance via phagocytosis...Conclusions We developed first-in-class anti-amyloidosis human CAR macrophages using CD34+ hematopoietic stem cells and confirmed their amyloid-targeting activities both in vitro and in vivo. Our data suggest that anti-AL amyloid CAR macrophages could be a promising novel cell therapy for AL amyloidosis."

Amyloidosis • Hematological Malignancies • Multiple Myeloma • Oncology • CD14 • CD33 • CD34 • CSF1 • PTPRC • SIRPA

Current and Emerging Immunotherapies for Systemic AL Amyloidosis. (PubMed, Discov Med) - "Quadruplet therapy of cyclophosphamide, bortezomib, dexamethasone and daratumumab (DaraCyborD) is the currently approved first-line induction therapy for systemic AL amyloidosis. Some patients need upfront autologous hematopoietic stem cell transplantation (HSCT) after high-dose melphalan conditioning particularly if DaraCyborD is not able to achieve complete hematologic response (CHR)...Both CAEL 101 and Birtamimab are currently being tested in phase 3 clinical trials for systemic AL amyloidosis patients with advanced cardiac involvement. This comprehensive review provides an up-to-date overview of AL amyloidosis therapy, with a particular focus on recent advances and future directions of immunotherapeutic strategies."

Journal • Review • Amyloidosis • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Transplantation

A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (clinicaltrials.gov) - P3 | N=281 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Mar 2027 ➔ Sep 2027

Trial completion date • Amyloidosis

A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (clinicaltrials.gov) - P3 | N=125 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Dec 2026 ➔ Oct 2027 | Trial primary completion date: Dec 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Amyloidosis

DEMOGRAPHIC AND BASELINE CHARACTERISTICS OF PATIENTS IN CARDIAC AMYLOID REACHING FOR EXTENDED SURVIVAL (CARES) PHASE 3 TRIALS ASSESSING SAFETY AND EFFICACY OF ANSELAMIMAB IN LIGHT CHAIN AMYLOIDOSIS (EHA 2024) - P3 | "The CARES program investigates thesafety and efficacy of anselamimab plus standard of care chemotherapy, cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab, in patients with European Modification of Mayo 2004 Stage IIIa andIIIb AL. With 406 enrolled patients with advanced stage AL amyloidosis, the CARES program includes the largestprospective study to date and the first global phase III study in stage IIIb patients. The study is ongoing untilthe pre-specified number of mortality events is reached."

Clinical • P3 data • Amyloidosis

AstraZeneca demonstrates commitment to patients living with amyloidosis at the 2024 International Symposium on Amyloidosis (ISA) (Businesswire) - P1 | N=46 | NCT04360434 | Sponsor: Neurimmune AG | "An encore poster presentation will report results from the first-in-human study of ALXN2220. Initial treatment with ALXN2220 was well tolerated with a transient increase in C-reactive proteins, suggesting initial targeted immune activation and recruitment of phagocytic immune cells. Additionally, an encore poster presentation will describe the pharmacokinetic and pharmacodynamic (PK/PD) model used for the selection of the dose range, dose escalation, dosing interval and study duration. Further, a poster will outline the baseline demographics and characteristics of the 406 participants of the Alexion CARES clinical program evaluating anselamimab in patients with Mayo Stage IIIa and IIIb AL amyloidosis..."

Clinical • P1 data • Amyloidosis • Cardiomyopathy • CNS Disorders

Novel monoclonal antibodies: A really specific therapy for light chain amyloidosis. (PubMed, Hematol Oncol) - "However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti-amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment."

Journal • Review • Amyloidosis • Hematological Disorders • Rare Diseases

Cael-101 Enhances the Clearance of Light Chain Fibrils and Intermediate Aggregates By Phagocytosis (ASH 2023) - "The phagocytotic activity is further enhanced in the presence of complement. In addition, for the first time we demonstrated that CAEL-101 was able to phagocytose intermediate soluble light chain aggregates, known precursors of amyloid fibril formation."

Amyloidosis • GLI2

Safety and Tolerability of Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study (ASH 2023) - P2, P3 | "Aims: To present safety, tolerability, and biomarker data after 110 weeks of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab. Patients in this analysis have been treated for ≥24 months and CAEL-101 was generally well tolerated without evidence of organ toxicity. Long-term safety evaluation of CAEL-101 continues in this study. Most TEAEs (85%) were mild to moderate."

Clinical • P2 data • Amyloidosis • Anemia • Cardiomyopathy • Cardiovascular • CNS Disorders • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Insomnia • Multiple Myeloma • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • Sleep Disorder • Transplantation • NPPB

A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (clinicaltrials.gov) - P3 | N=267 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2025 ➔ Mar 2027

Enrollment closed • Trial completion date • Amyloidosis

A Study to Evaluate the Safety and Tolerability of CAEL-101 in Patients With AL Amyloidosis (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Alexion Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Amyloidosis

A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (clinicaltrials.gov) - P3 | N=124 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2026

Enrollment closed • Trial completion date • Amyloidosis

CAEL-101 in Real AL Amyloidosis (SWOG-Fall 2023) - No abstract available

Amyloidosis

Safety And Tolerability Of Cael-101, An Anti-amyloid Monoclonal Antibody, Combined With Anti-plasma Cell Dyscrasia Therapy In Patients With Light-chain Amyloidosis: 18-month Results Of A Phase 2 Study (HFSA 2023) - P2 | "CAEL-101 is a novel, investigational, potentially first-in-class therapy to remove these fibrils from organs.Hypothesis: CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab, is well-tolerated up to 18 months in patients with AL amyloidosis. Adult patients with AL amyloidosis (European Modification of Mayo Stage I-IIIa) and measurable hematologic disease were eligible for This ongoing, open-label, phase 2 study (NCT04304144). Currently enrolled patients have been treated for ≥18 months. CAEL-101 was generally well-tolerated with no evidence of organ toxicity. Most TEAEs were mild to moderate."

Clinical • P2 data • Amyloidosis • Heart Failure • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • NPPB

Orphan Designation: Treatment of transthyretin amyloidosis (FDA) - Date Designated: 10/02/2023

Orphan drug • Amyloidosis • CNS Disorders

Fortress Biotech Reports Second Quarter 2023 Financial Results and Recent Corporate Highlights (GlobeNewswire) - "CAEL-101 (Light Chain Fibril-reactive Monoclonal Antibody for AL Amyloidosis)....Based on its public statements, AstraZeneca has estimated that it expects the FDA to accept its BLA submission for review in the second half of 2024."

BLA • Amyloidosis • CNS Disorders

CARDIAC AMYLOID REACHING FOR EXTENDED SURVIVAL (CARES) TRIALS: 2 PLACEBO-CONTROLLED, DOUBLE-BLIND, RANDOMIZED, PHASE 3 TRIALS ASSESSING CAEL-101 IN PATIENTS WITH MAYO STAGES IIIA/IIIB AL AMYLOIDOSIS (EHA 2023) - P3 | "AL amyloidosis, Treatment, Antibody"

Clinical • P3 data • Amyloidosis • Hematological Disorders • Hypotension

SAFETY AND TOLERABILITY OF CAEL-101, AN ANTI-AMYLOID MONOCLONAL ANTIBODY, COMBINED WITH ANTI-PLASMA CELL DYSCRASIA THERAPY IN PATIENTS WITH LIGHT-CHAIN AMYLOIDOSIS: 18-MONTH RESULTS OF A PHASE 2 STUDY (EHA 2023) - P2 | "Aims: To present safety, tolerability, and biomarker data for 18 months of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab. Currently enrolled patients have been treated for ≥18 months and CAEL-101 was generally well tolerated without evidence of organ toxicity. Long-term safety evaluation of CAEL-101 continues in this study. Most TEAEs were mild to moderate."

Clinical • P2 data • Amyloidosis • Heart Failure • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • NPPB

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis. (ASCO 2023) - P3 | "Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825, NCT04512235."

Clinical • P3 data • Amyloidosis • Hematological Disorders • Hypotension • Rare Diseases

Updated OS of patients with AL amyloidosis after CAEL-101. (ASCO 2023) - P1a/1b | "Patients with relapsed/refractory AL amyloidosis who received a low cumulative amount of the novel anti-amyloid CAEL-101 in a phase 1a/1b study had lengthy overall and progression-free survival compared to historical controls. Patterns of organ progression after initial response may reflect intrinsic differences in organ vulnerability. The CAEL101-301 and CAEL101-302 phase 3 clinical trials are underway to confirm these findings."

Clinical • Amyloidosis • Cardiovascular • Hematological Disorders • Transplantation • Venous Thromboembolism

"Thanks so much @awechalekar - the Cael-101 first in human critical trial was for sure one of the most interesting endeavors in my academic life!" (@SLentzsch)

P1 data

Randomized Phase II of CAEL-101 vs Placebo in Renal AL Amyloidosis. Amyloid two-arm study (SWOG-Spring 2023) - No abstract available

Clinical • P2 data • Amyloidosis