Enjaymo provides lasting CAD control even with fewer doses: Study
In real world, infusion therapy quickly eased anemia in hard-to-treat cases
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For people with hard-to-treat cold agglutinin disease (CAD), long-term treatment with Enjaymo (sutimlimab-jome) may offer lasting disease control, even with less frequent infusions than recommended, according to a small real-world study in Italy.
Enjaymo was found to quickly reduce red blood cell destruction, ease anemia, and eliminate the need for blood transfusions in four patients whose disease had not responded to multiple previous treatments.
These benefits were sustained for nearly two years, even after doctors extended the dosing schedule from the approved every-two-week regimen to once-monthly infusions, data show.
These findings provide “real-life evidence that [Enjaymo] induces rapid, durable responses even in multi-refractory patients” — individuals who failed to respond to multiple CAD treatments, the researchers wrote.
But while the extended-interval dosing “proved highly effective and well tolerated” in their small group of patients, the scientists cautioned that spacing out doses “should be individualized and cannot be generalized to all patients.”
Titled “Sutimlimab for Relapsed Cold Agglutinin Disease: Real-Life Evidence of Sustained Response With Extended-Interval Dosing,” the study was published as a letter to the editor in the European Journal of Haematology.
CAD occurs when self-reactive antibodies mistakenly attach to red blood cells at low temperatures, triggering activation of the complement system, a part of the immune system. This leads to the destruction of red blood cells, a process known as hemolysis, which can cause symptoms of anemia, a condition characterized by low red blood cell counts.
Enjaymo given to 4 patients in compassionate-use program
In people with CAD, rituximab, an immunosuppressive medication that lowers the number of antibody-producing immune cells, is often used as a first-line treatment. However, many patients either relapse — meaning the disease returns — or the condition is refractory, meaning it does not respond adequately to the therapy, which also is given via infusions.
Enjaymo, the only approved treatment for CAD, is designed to specifically block C1s, a key protein in the classical complement pathway. By selectively targeting this complement pathway, the therapy can reduce hemolysis without broadly suppressing the immune system. It is administered via an intravenous (into-the-vein) infusion once weekly for the first two weeks, and every two weeks thereafter.
Its approval was based on data from a pair of Phase 3 clinical trials: CARDINAL (NCT03347396) and CADENZA (NCT03347422). These studies showed that Enjaymo rapidly raised hemoglobin levels and reduced the need for blood transfusions among people with CAD. Hemoglobin is the oxygen-carrying protein in red blood cells.
More recently, a real-world study in Germany reported that long-term treatment with Enjaymo sustained reductions in hemolysis and maintained stable hemoglobin levels among patients for nearly two years. People on the therapy also avoided blood transfusions over that timeframe.
In response to those findings, a team of researchers in Italy described their long-term outcomes of four adults with refractory CAD who received Enjaymo under a compassionate-use program. Such a program allows patients with serious or life-threatening diseases to access therapies before they are fully approved in their country, typically when other options have failed.
The patients had a median age of 68 — ranging from 38 to 81 — and longstanding disease that had not responded well to multiple previous treatments, including repeated courses of rituximab. In all cases, prior responses had been incomplete or transient.
The four received recommended vaccinations before starting Enjaymo, according to the suggested schedule. Each was monitored every two weeks with blood tests measuring hemoglobin and hemolysis markers. All patients initially received the approved Enjaymo regimen.
Patients no longer needed blood transfusions after 1-2 weeks
At the start of treatment, median hemoglobin levels showed anemia. After starting Enjaymo, hemoglobin levels rose quickly and all patients became independent from blood transfusions within one to two weeks. Blood markers of hemolysis, including bilirubin, also returned to normal early after starting Enjaymo.
After about two months, once patients had achieved stable responses, doctors changed their Enjaymo maintenance schedule from the approved every-two-week scheme to one infusion every four weeks.
Even so, the monthly schedule remained both well tolerated and highly effective, the researchers reported. No loss of benefit was seen, no severe infections were reported, and infusion tolerance remained excellent across all patients.
Our compassionate-use experience, including off-label interval extension, supports and extends the findings of [a previous real-world study in Germany], providing real-life evidence that [Enjaymo] induces rapid, durable responses even in multi-refractory patients.
At the last follow-up, after a median treatment duration of 23 months, or nearly two years, three of the individuals were still on Enjaymo, with sustained responses. One patient, age 76, died from surgical complications unrelated to CAD or Enjaymo.
Two patients temporarily stopped Enjaymo’s monthly treatment for reasons unrelated to CAD. Both showed blood test changes indicating relapse shortly after stopping therapy.
When Enjaymo was restarted on the standard dosing schedule, blood tests quickly returned to normal, “after which monthly maintenance was successfully resumed,” the researchers wrote.
“Our compassionate-use experience, including off-label interval extension, supports and extends the findings of [the previous real-world study in Germany], providing real-life evidence that [Enjaymo] induces rapid, durable responses even in multi-refractory patients,” the researchers wrote.
They emphasized, however, that “larger observational studies will be essential to better define long-term management strategies for patients with CAD.”
