Enjaymo Reduces Anemia, Fatigue in Phase 3 CADENZA Trial

The therapy this year became the first approved in the US to treat adults with CAD

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Enjaymo (sutimlimab-jome) eased anemia, and reduced fatigue and the need for blood transfusions and other treatments in people with cold agglutinin disease (CAD) who hadn’t received blood transfusions recently, final results from the Phase 3 CADENZA trial show.

Results were detailed in the study, “Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial,” published in Blood. The work was funded by Sanofi, which markets Enjaymo, an antibody-based treatment designed to prevent the activation of the complement cascade. The complement cascade is a group of immune proteins that play a role in the inflammatory attack that damages red blood cells in CAD. It specifically targets a complement protein called C1.

Earlier this year, Enjaymo became the first treatment to be approved for adults with CAD in the U.S. The approval was supported by data from the Phase 3 CARDINAL trial (NCT03347396), which showed it was able to increase hemoglobin levels, prevent red blood cell destruction, and improve the quality of life for patients who had received a blood transfusion in the six months before entering the study.

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CADENZA (NCT03347422) tested Enjaymo in adults with CAD who had not received a blood transfusion recently. The two-part study enrolled 42 participants at 53 sites across 14 countries. Participants’ demographics were largely reflective of the overall CAD population: about three-quarters were female, with a median age of 66.

In part A, which is now complete, participants were randomly assigned to receive Enjaymo (dosed according to body weight) or a placebo, given via infusion on study days 0 and 7, then every other week for 26 weeks (about six months).

“CADENZA is the first placebo-controlled trial of [Enjaymo] in CAD and strengthens the results from the previous single-arm open-label CARDINAL study of patients with CAD and recent transfusion history,” the researchers wrote.

Three participants, all in the Enjaymo group, discontinued the trial early due to side effects. The remaining participants all completed the 26-week study and have entered into its open-label extension, where all are being treated with Enjaymo.

The study’s main goal was to compare the proportion of participants who met a composite endpoint — defined as an increase in hemoglobin levels of at least 1.5 g/dL by the end of part A, plus being free from blood transfusions or other CAD medications from week five on.

As previously reported, most (72.7%) patients in the Enjaymo group met this composite endpoint, while only 15% of those in the placebo group did. CAD patients treated with Enjaymo were nearly 16 times more likely to meet this endpoint after 26 weeks of treatment than those given a placebo, according to statistical analyses.

Three patients in the Enjaymo group completed the 26-week study, but did not meet the primary endpoint. Specifically, none showed a sufficiently high increase in hemoglobin levels, and one received a blood transfusion during the study.

More than 80% of the patients in both treatment groups did not require blood transfusions from week 5 to week 26. Likewise, 86.4% of patients in the Enjaymo group and all those in the placebo group did not require CAD medications that were prohibited under CADENZA’s protocol.

Enjaymo generally boosted hemoglobin levels and reduced signs of red blood cell destruction (hemolysis) within about three weeks of starting treatment, analyses of trial data over time suggested. These benefits were sustained throughout the entire study.

The proportion of patients achieving a hemoglobin level equal to or higher than 11 g/dL was much higher among those treated with Enjaymo than in those given a placebo (73.7% vs. 20%). Similarly, the proportion of patients whose hemolysis markers, including bilirubin and lactate dehydrogenase, normalized was much higher in the Enjaymo group than in the placebo group.

Patients also reported clinically meaningful reductions in fatigue (measured via FACIT-Fatigue scores) that were apparent within a week of starting treatment and were maintained throughout the study.

Researchers concluded Enjaymo “led to normalization of mean [hemoglobin] levels and markers of hemolysis, and clinically meaningful improvements in fatigue in patients with CAD without a history of recent blood transfusion.”

The most common side effects related to Enjaymo were headache, high blood pressure, nasal congestion, Raynaud phenomenon, and acrocyanosis (bluish discoloration of the skin). Rates of infections were similar in both the Enjaymo and placebo groups, and no deaths were reported during the study.