Updated Organ Response Results of an Open-Label Study to Evaluate the Safety and Tolerability of Cael-101 in Patients with AL Amyloidosis Receiving Anti-Plasma Cell Therapy

Background: CAEL-101 is an IgG1 monoclonal antibody intended to enable immune clearance of AL amyloid deposits. This study (NCT04304144) data allowed dose selection of CAEL-101 for the ongoing Phase 3 studies in patients with Mayo stage IIIa and IIIb AL amyloidosis cardiomyopathy newly diagnosed and treated with bortezomib, cyclophosphamide, and dexamethasone (CyBorD) alone or in combination with daratumumab.

Methods: 13 patients were treated with CAEL-101 and CyBorD and an additional 5 patients were treated with CAEL-101, daratumumab, and CyBorD. Organ response data on assessable patients were evaluated per consensus criteria as per institutional standard of care. Safety, pharmacokinetic and anti-drug antibody data will be reported separately.

Results: The follow up for patients receiving CAEL-101 and CyBorD is 12 to 15 months and for the CAEL-101, Daratumumab, and CyBorD is 4 to 6 months. 16 of 18 patients remain on treatment. One discontinuation was due to death from E. coli sepsis and the other due to lack of hematologic response with deterioration of heart function requiring heart transplant after only 6 doses of CAEL-101. Organ response in cardiac patients by NT pro BNP criteria occurred in 4 of 8 evaluable patients treated with CAEL-101 and CyBorD (time to organ response range 2 - 12 months) and in 2 of 3 patients treated with CAEL-101, daratumumab, and CyBorD (time to organ response range 3 - 5 months). Four patients have had repeat echocardiogram 1 year from start of CAEL-101 based therapy with interpretable global peak longitudinal strain (GLS). The GLS improved in 2 patients by -5% (-6.4% to -11.4%) and -5.1% (-12.8% to -17.9%). GLS remained stable in the other 2 patients. All 9 patients with evaluable kidney involvement by 24 hour urine protein achieved an organ response. Responses occurred in as little as 2 months in 5 patients (range 2 - 7 months). The time to organ response were similar in the daratumumab and non-daratumumab treated patients. One patient with hematologic stable disease and persistent 71% improvement in 24 hour urine protein at 10 months from start of CAEL-101 based therapy is most notable.

Conclusions: CAEL-101 with anti-plasma cell therapy remains reasonably well tolerated with no unanticipated adverse effects. Organ responses, most notably renal response, have occurred early in the course of therapy and appears to be durable. Organ responses in some patients have also improved over time with some significant improvement in patient GLS evaluations by echocardiogram. These results encourage clinical trial participation in the ongoing CAEL-101 clinical trials in Mayo stage IIIa and IIIb AL amyloidosis patients.