Life quality gains with Enjaymo sustained for 2.5 years
Researchers share long-term results of Phase 3 CARDINAL trial for CAD
Long-term treatment with Enjaymo (sutimlimab-jome) led to sustained improvements in life quality and reductions in fatigue for people with cold agglutinin disease (CAD), according to 2.5 years of data from the Phase 3 CARDINAL clinical trial.
“[Enjaymo] provides sustained and durable treatment benefits in chronic CAD, including a continued meaningful impact on patient [quality of life] in the long term,” the researchers wrote.
However, these benefits tended to decline in the months after the study was completed and treatment was discontinued.
The study, “Long-term sutimlimab improves quality of life for patients with cold agglutinin disease: CARDINAL 2-year follow-up,” was published in Blood Advances.
In CAD, the immune system wrongly attacks and destroys red blood cells at low temperatures. Consequently, patients experience anemia, which is a loss of healthy red blood cells that are needed to transport oxygen throughout the body.
Enjaymo is an antibody-based therapy that works to prevent activation of the classical complement pathway, an immune system signaling cascade that is implicated in CAD’s autoimmune attacks. It does so by blocking C1s, a key protein in the classical complement pathway.
Administered directly into the bloodstream, the therapy is approved in both the U.S. and Europe for adult CAD patients, regardless of whether they previously received blood transfusions due to red blood cell destruction (hemolysis).
Approvals were based partially on data from the two-part Phase 3 CARDINAL trial (NCT03347396), which tested the therapy in 24 adults with CAD who had a recent history of blood transfusions.
In the study’s first part, all participants, with a median age of 71.5, received a weight-based dose of Enjaymo once a week for the first two weeks, and once every two weeks for up to about six months. Results showed that Enjaymo was able to prevent hemolysis, ease anemia and fatigue, and improve life quality for trial participants.
A total of 22 participants then moved on to the trial’s second portion, where they were treated with Enjaymo every other week for an additional two years — totaling 2.5 years of treatment — to evaluate the therapy’s long-term effects.
Findings from this part of the trial indicated the therapy’s favorable safety profile, as well as reductions in hemolysis, anemia, and fatigue, were sustained for the 2.5 years of treatment. At a follow-up about two months after treatment ended, patients showed a worsening of these symptoms.
Long-term results
Now, scientists described detailed long-term results of CARDINAL’s patient-reported outcome measures.
As previously reported, Enjaymo led to sustained reductions in patient-reported fatigue, as assessed with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale, in which higher scores indicate less fatigue.
FACIT-Fatigue score changes were considered clinically meaningful throughout the trial, meaning they reflected an increase of at least five points from the study’s start, or baseline (range, 6.8-12.1 points).
At a follow-up a little more than two months after stopping treatment, FACIT-Fatigue values were just one point above baseline values, failing to meet the cutoff.
Data from an exploratory measure of fatigue — the Patient Global Impression of Severity — similarly indicated reductions in fatigue severity after 2.5 years. While about a third of patients reported severe fatigue at baseline, no patient reported this level of severity by the end of treatment, with 80% experiencing only mild fatigue or none at all.
Assessing health’s effects on daily life
Changes in physical and mental subscores on the 12-item Short Form Health Survey (SF-12), a measure of the impacts of health on daily life, met their respective clinically-meaningful thresholds at the last general assessment, at about 2.3 years, indicating gains in life quality.
While physical scores remained above the cutoff for clinically meaningful change throughout that time, mental scores fluctuated above and below the threshold from one year of treatment onward.
“The mental component of the SF-12 might be affected by social or personal factors unrelated to the disease state … which may have impacted the data due to the small sample size,” the researchers wrote.
Other life quality measures also showed quick improvements after Enjaymo initiation that were sustained through 2.5 years, but declined following treatment discontinuation.
According to the Patient Global Impression of Change, 86.7% of patients experienced a reduction in disease burden by the end of the treatment period. This proportion was reduced to 65% two months after treatment discontinuation, at which point about 15% of patients reported disease worsening.
‘Positive impact on patient well-being’
“Overall, C1s inhibition had a positive impact on patient well-being as recorded by [patient-reported outcomes],” the researchers wrote, adding that “this impact on patient experience is an important factor for clinical decision-making when treating a disease with a heavy burden on patient [quality of life].”
Additionally, the fact that most of these measures deteriorated after ending treatment favors “the recommendation that patients should remain on treatment,” they added.
The scientists noted that the relationship between reductions in anemia and hemolysis with Enjaymo, and changes in these subjective life quality benefits, needs more investigation.
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