Enjaymo Eases Fatigue, Improves Quality of Life, Trial Data Shows
The results add to previous data that show the therapy prevented hemolysis, anemia, need for blood transfusions
Enjaymo (sutimlimab-jome) led to clinically relevant reductions in fatigue and improvements in quality of life in adults with primary cold agglutinin disease (CAD), according to additional six-month data from Part A of the Phase 3 CARDINAL trial.
These benefits in several patient-reported outcomes add to previously reported data showing the therapy prevented red blood cell destruction (hemolysis), anemia, and the need for blood transfusions, which supported its approval in the U.S. Health authorities in Europe and Japan are also deciding whether to approve the therapy to treat CAD.
These findings further support Enjaymo’s therapeutic potential in this patient population.
The data were detailed in the study, “Sutimlimab improves quality of life in patients with cold agglutinin disease: results of patient-reported outcomes from the CARDINAL study,” published in Annals of Hematology.
In CAD, the immune system produces self-reactive antibodies that bind to red blood cells when exposed to cold temperatures, promoting immune reactions that result in their destruction.
This ultimately leads to hemolytic anemia — a blood disorder wherein red blood cells are destroyed faster than they can be replaced — which is responsible for most CAD symptoms.
CAD is also associated with poor quality of life, with patients showing fatigue levels “comparable to chronic illnesses such as cancer and other hemolytic anemias,” the researchers wrote. The disease usually develops in older adults, increasing the likelihood of simultaneous conditions that may further affect their quality of life.
Previous CAD-related studies rarely included patient-reported outcomes (PROs) of quality of life and fatigue, however. There’s also a limited understanding about the link between treatment-induced reductions in hemolysis and changes in these outcomes.
Part A of the global Phase 3 CARDINAL trial (NCT03347396), which tested six months of treatment with Enjaymo in 24 adults with CAD and a recent history of blood transfusion, included PROs as secondary goals.
Developed by Sanofi’s subsidiary Bioverativ, Enjaymo works by selectively suppressing C1 protein activity. C1 plays a key role in the classical complement pathway, a part of the immune system that’s overactive in CAD and implicated in its associated hemolysis.
The therapy is administered directly into the bloodstream at weight-based doses every week for two weeks, and every other week thereafter.
Previous results showed the therapy safely and rapidly increased hemoglobin levels and reduced the need for blood transfusions — meeting its main goal. Hemoglobin is the protein in red blood cells that transports oxygen throughout the body.
Patient responses to Enjaymo
Newly published results concern the impact of Enjaymo on CARDINAL’s PRO-based secondary measures, which included the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score and in exploratory, health-related quality of life measures.
These comprised the 12-Item Short Form Health Survey (SF-12), which includes physical and mental component scores; the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L); the Patient Global Impression of Change (PGIC); and the Patient Global Impression of (fatigue) Severity (PGIS).
Data at the study’s start (baseline) showed 91.7% of patients, who had a mean age of 71 (range 55–85), had at least one ongoing/resolved medical history. These included surgical and medical procedures, heart disorders, infections and infestations, and gastrointestinal disorders (all affecting more than 45% of patients).
Also, participants showed severe fatigue and “consistently abnormal measures of QOL [quality of life] at baseline,” the researchers wrote, further emphasizing the poor quality of life of this patient population.
Patients’ mean FACIT-Fatigue scores increased rapidly with Enjaymo treatment from week 1, indicating fewer fatigue symptoms. Scores peaked at week 7 and improvements were sustained through week 26 (about six months), consistently surpassing clinically meaningful thresholds.
Clinically important increases in the FACIT-Fatigue score (of three or more points) were detected in at least 75% of patients. One patient who missed a dose had a FACIT-Fatigue score decline of 44%, which was associated with a rise in classical complement activity by almost 70%.
Clinically meaningful improvements in both SF-12 physical and mental component scores were also detected at week 5 and sustained throughout treatment. These gains were associated with a near-complete reduction in classical complement activity.
Quality of life, as assessed with the EQ-5D-5L, was also considerably improved, with a reduction in the “proportion of patients reporting ‘moderate, severe, or extreme’ (as opposed to ‘no or slight’) problems” after treatment, the research team wrote.
Moreover, 94% of patients who completed the PGIC said they felt treatment had eased their disease and none reported disease worsening. The proportion of patients reporting moderate to severe fatigue in PGIS dropped from 67% to 0% after treatment.
Enjaymo treatment was also associated with a reduction in some CAD-related symptoms and in anemia symptoms. Among the latter, the frequency of fatigue dropped from 75% to 26.3%, weakness from 62.5% to 15.8%, shortness of breath from 54.2% to 15.8%, palpitations from 29.2% to 0%, and chest pain from 8.3% to 5.3%.
“This is the first study to report substantial improvements in PROs for patients receiving classical CP [complement pathway] inhibition therapy for CAD,” the researchers wrote.
While the small patient number limited the analyses’ power to detect statistically significant changes, the study provides strong evidence of Enjaymo’s ability to sustainably lessen fatigue and improve patients’ overall quality of life, they said.
The observed improvements in PROs suggest that “classical CP activation and subsequent hemolysis may be key drivers of fatigue and poor QOL in patients with CAD,” the researchers wrote, noting this further supports the effectiveness of Enjaymo and other approaches “targeting upstream CP components in the management of patients with CAD.”