Real-world study confirms long-term safety of Enjaymo for CAD
New 2-year CADENCE data support use of approved therapy
Enjaymo (sutimlimab-jome) remains safe to use over the long term, according to new real-world data from adults with primary or secondary cold agglutinin disease (CAD) who have been taking the approved medication for an average of more than two years.
The data come from CADENCE (NCT05791708), an ongoing registry that is following 442 patients — including more than 60 given Recordati’s Enjaymo — at sites in the U.S., Europe, and Japan.
“The CADENCE registry data expand upon the real-world evidence base supporting the use of [Enjaymo] for patients with [CAD],” Alessandro Albuquerque, MD, PhD, Recordati’s chief medical officer and vice president of medical affairs and clinical development, said in a press release by Recordati Rare Diseases, the company’s business unit focused on rare diseases.
“We look forward to additional updates from the CADENCE registry as follow-up continues,” Albuquerque said.
While CADENCE is expected to be completed by the end of 2028, final results are not anticipated until 2031, according to a poster shared at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, held Dec. 6-9 in Orlando, Florida, and virtually. The abstract was titled “Real-world safety of sutimlimab in patients with CAD/CAS: A multinational, multi-center, observational, prospective cohort study.”
CAD is caused by self-reactive antibodies called cold agglutinins. These antibodies bind to red blood cells at low temperatures and active the complement system — an immune cascade where one protein activates the next — ultimately leading to hemolysis, or red blood cell destruction.
Enjaymo approved in US for primary and secondary CAD
There are two main types of CAD. Primary CAD, often referred to simply as CAD, occurs without a known cause. Secondary CAD, also known as cold agglutinin syndrome (CAS), develops as a complication of another condition, usually an infection, blood cancer, or an autoimmune disease.
Treatment for CAD typically focuses on reducing hemolysis or the production of self-reactive antibodies. In contrast, CAS treatment usually involves treating the underlying cause.
Enjaymo, the only CAD-approved therapy, is designed to prevent hemolysis and ease symptoms of CAD by selectively blocking the activity of the complement C1 protein. It is not approved for CAS, and its safety and efficacy in CAS have yet to be established.
CADENCE was designed to document treatment patterns and regimens in people with any type of CAD in the real-world practice.
“The CADENCE registry comprises the world’s largest dataset of treatment patterns and regimens, … offering a unique, real-world view of how patients respond to long-term therapy,” said Catherine M. Broome, MD, a professor at Medstar Georgetown University in Washington and the registry’s lead investigator.
No new safety concerns ID’d in real-world use
The newly announced data concerned 63 participants who had been treated with Enjaymo for a mean of 25.1 months, or slightly longer than two years. Of these patients, 58 were diagnosed with CAD, four with CAS, and one had a yet unconfirmed diagnosis. Their mean age was 72.7, and about three-quarters were women.
A total of 159 adverse events were reported in about half (52.4%) of these patients. Six participants (9.5%) experienced adverse events that were considered related to Enjaymo. Serious adverse events were reported in 11 patients (17.5%), and one — chest pain in a person with CAS — was viewed as unexpectedly related to Enjaymo.
Safety findings are consistent with earlier clinical trial data and continue to support the long-term safety profile of [Enjaymo].
Adverse events of special interest included serious infections in three people and high blood pressure in two, but these were deemed unrelated to the therapy. Three of these patients had previously received rituximab, an immunosuppressive medication that depletes the immune cells responsible for producing antibodies, including those that are self-reactive.
One participant died from pneumonia but this was determined to be unrelated to treatment.
Acrocyanosis, a CAD symptom marked by bluish discoloration of the skin, occurred in eight patients, and two were possibly related to Enjaymo, according to the team.
“After a mean treatment duration of over 2 years, no new safety concerns were identified in this updated analysis of CADENCE registry patients with CAD and CAS chronically treated with [Enjaymo],” the researchers wrote. “Safety findings are consistent with earlier clinical trial data and continue to support the long-term safety profile of [Enjaymo].”
Still, because CADENCE is a registry rather than a controlled clinical study, the findings are descriptive and should be interpreted carefully, the company noted in the release.
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