Long-term Enjaymo use shows favorable outcomes in CAD: Study
Patients maintained stable hemoglobin levels, avoided blood transfusions
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People with cold agglutinin disease (CAD) treated long-term with Enjaymo (sutimlimab-jome) maintained stable hemoglobin levels, avoided blood transfusions, and showed sustained reductions in red blood cell destruction for nearly two years, according to a real-world, single-center study from Germany.
“The present small, [single-center] study confirms the efficacy and acceptable rate of side effects of [Enjaymo] in CAD patients,” researchers wrote.
The study, “Sutimlimab in Patients With Cold Agglutinin Disease (CAD): Results From a Managed Access Program,” was published in the European Journal of Haematology.
Enjaymo reduces red blood cell destruction
CAD is a rare autoimmune disorder caused by self-reactive antibodies that mistakenly attach to red blood cells at low temperatures. This triggers the activation of the complement system, a part of the immune system, leading to hemolysis, or red blood cell destruction.
Until recently, there was no approved therapy for CAD, and doctors relied on treatments such as rituximab, an immunosuppressive medication that reduces the number of immune cells that produce antibodies.
That changed with the approval of Enjaymo, a first-in-class antibody that blocks C1s, a key protein in the classical complement pathway. By preventing the activation of this complement pathway, Enjaymo can reduce red blood cell destruction without suppressing the entire complement system.
Its approval was based on data from two Phase 3 trials — CARDINAL (NCT03347396) and CADENZA (NCT03347422) — that showed the therapy could rapidly increase hemoglobin levels and reduce the need for transfusions. Hemoglobin is the protein that carries oxygen in red blood cells.
Hemoglobin levels rose in 9 out of 10 patients treated with Enjaymo
In this study, researchers evaluated the therapy’s effectiveness over nearly two additional years in patients who had completed the original Phase 3 trials, as well as the outcomes of newly treated patients.
The analysis included 10 patients with primary CAD. They had a median age of 70.5 years, and the majority (80%) were women. All patients received Enjaymo for 96 weeks, or roughly 1.8 years, as part of a managed access program at the University Hospital of Essen, Germany. A managed access program allows patients with serious diseases to have early access to investigational or unapproved therapies.
Eight patients had participated in the previous Phase 3 trials, while the remaining two had never been treated with Enjaymo. Those who had previously received the medication were given the therapy again after a washout period lasting a median of 12.6 weeks, or about three months.
Although our investigation did not comprise a control group, it strongly backs the conclusion that [Enjaymo] can be recommended as a first-line therapy for symptomatic hemolytic CAD patients.
After starting treatment with Enjaymo, hemoglobin levels rose quickly in all patients except one, and remained stable throughout the nearly two years of follow-up. Median hemoglobin levels increased from 9.8 g/dL at the start of treatment (baseline) to 10.6 g/dL after two weeks. Normal or near-normal levels were observed after four weeks (median of 12.2 g/dL) and were maintained until the end of follow-up (median of 12.5 g/dL).
No patient required blood transfusions during this period.
Other laboratory measures also indicated a strong and sustained reduction in hemolysis. Levels of bilirubin — a byproduct of red blood cell destruction — returned to normal by week two and stayed largely within the normal range through to the end of the study. Reticulocyte counts, or the number of immature red blood cells that reflect the bone marrow’s response to anemia, fell substantially over time, indicating a reduction in red blood cell loss.
Importantly, no new cold-induced circulation problems were reported during treatment. Enjaymo was generally well tolerated, with no cases of meningococcal or pneumococcal infections and no treatment-related serious adverse events recorded. One patient died after 3.7 months due to complications from an underlying cardiovascular condition, which investigators deemed to be unrelated to Enjaymo.
“Although our investigation did not comprise a control group, it strongly backs the conclusion that [Enjaymo] can be recommended as a first-line therapy for symptomatic hemolytic CAD patients,” the researchers wrote.
