FDA Approves Sutimlimab-jome with Long-Term Safety, Efficacy Data for Cold Agglutinin Disease

The FDA has approved an expanded label for sutimlimab-jome (Enjaymo, Sanofi) with new long-term safety and efficacy data for individuals with cold agglutinin disease (CAD), to now include patients with or without a history of transfusions.

The efficacy supplemental Biologics License Application was evaluated under priority review and included long-term data from the pivotal CADENZA and CARDINAL trials. Sutimlimab-jome was first approved by the FDA in February 2022 based on data from Part A of the CARDINAL study, which was a single arm, open-label study in patients with CAD with a blood transfusion in the past 6 months.

Sutimlimab-jome is currently the only approved treatment of hemolysis for CAD. It is a first-in-class humanized monoclonal antibody designed to selectively target and inhibit the classical complement pathway specific serine protease, C1s. By blocking C1s of the classical complement pathway, sutimlimab-jome inhibits C1-activated hemolysis in CAD to prevent hemolysis, while leaving the lectic and alternative pathways intact.

The expanded prescribing information is primarily based on the phase 3 CADENZA study, a double-blind, placebo-controlled clinical trial of adults with CAD, without a recent history of blood transfusion. The trial met its primary composite endpoint, demonstrating inhibition of hemolysis as well as avoidance of transfusions and use of CAD-related treatments. Data from secondary endpoints showed an increase in hemoglobin levels, decrease in bilirubin levels, and reduced lactate dehydrogenase levels.

Patients who received sutimlimab-jome also reported a statistically significant improvement in symptoms and impacts of fatigue, which was measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Overall safety results were consistent with the safety profile of sutimlimab-jome from the CARDINAL study.

Part B of the CARDINAL and CADENZA studies demonstrated the long-term safety as well as durability of response to sutimlimab-jome in patients with CAD over a 2-year follow up and 1-year follow up, respectively. In both of these studies, signs and symptoms of recurrent hemolysis were observed 9 weeks after the last dose of sutimlimab-jome in part B.

The most common adverse events (AEs) in part A of the CADENZA study (incidence 18% or greater) were rhinitis, headache, hypertension, acrocyanosis, and Raynaud’s phenomenon. In the CARDINAL study, the most common AEs (incidence 25% or greater) were urinary tract infection, respiratory tract infection, bacterial infection, dizziness, fatigue, peripheral edema, arthralgia, cough, hypertension, and nausea.

Under the expanded label, sutimlimab-jome is now also available in an undiluted preparation, which can decrease the bi-weekly infusion time to 1 hour.

“As a first-in-class therapy, Enjaymo can help people living with cold agglutinin disease better manage their symptoms, including the impact of fatigue, which may positively affect their daily life,” said Bill Sibold, MBA, executive vice president and head of specialty care at Sanofi, in a press release.

CAD is a chronic, rare blood disorder that impacts an estimated 5000 individuals in the United States. It is caused by antibodies called cold agglutinins, which bind to the surface of red blood cells and cause the immune system to mistakenly attack healthy red blood cells and cause hemolysis. Patients with CAD may experience severe anemia, resulting in fatigue, weakness, shortness of breath, light-headedness, chest pain, irregular heartbeat, and other potential complications.

REFERENCE

FDA approves expanded label of Enjaymo (sutimlimab-jome) to include long-term safety and efficacy for people with cold agglutinin disease. News release. Sanofi; January 25, 2023. Accessed January 30, 2023. https://www.news.sanofi.us/2023-01-15-FDA-approves-expanded-label-of-Enjaymo-R-sutimlimab-jome-to-include-long-term-safety-and-efficacy-for-people-with-cold-agglutinin-disease