FDA Approves Sanofi’s Enjaymo for Rare Anemia

The U.S. Food and Drug Administration approved Sanofi’s Enjaymo to decrease the need for red blood cell transfusion due to hemolysis in adults with cold agglutinin disease, a rare form of anemia.

Photo: Bill Sibold, executive vice president, head of Specialty Care at Sanofi

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia that is caused by antibodies called cold agglutinins binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). As red blood cells have the vital job of carrying oxygen throughout the body, patients with CAD may experience severe anemia, which can result in fatigue, weakness, shortness of breath, light-headedness, chest pain, irregular heartbeat, and other potential complications. CAD is a chronic and rare blood disorder that impacts the lives of an estimated 5,000 people in the United States.

Enjaymo (sutimlimab-jome) is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells without inhibiting the lectin and alternative pathways. Enjaymo is the first and only approved treatment for people with CAD and works by inhibiting the destruction of red blood cells (hemolysis).

“Until now, people living with cold agglutinin disease haven’t had an approved treatment option to manage the constant destruction of red blood cells,” said Bill Sibold, executive vice president, head of Specialty Care at Sanofi. “Without healthy, viable red blood cells, a chain reaction of debilitating signs and symptoms can be triggered, starting with severe anemia. Enjaymo is the only approved treatment to inhibit red blood cell destruction in CAD and help stop the chain reaction from the start.”

FDA’s approval of Enjaymo is based on positive results from the 26-week open label, single arm pivotal CARDINAL pPhase 3 study in patients with CAD who have a recent history of blood transfusion.

In the study, Enjaymo met its primary efficacy endpoint, which was a composite endpoint defined as the proportion of patients who achieved normalization of hemoglobin (Hgb) level ≥12 g/dL or demonstrated an increase from baseline in Hgb level ≥2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26 or medications prohibited per the protocol from weeks 5 through 26. Secondary endpoints were also met, including improvements in hemoglobin and normalization of bilirubin.

The majority of patients (54 percent) met the composite primary endpoint criteria with 63 percent of patients achieving a hemoglobin ≥ 12 g/dL or an increase of at least 2 g/dL; 71 percent of patients remaining transfusion-free after week five; and 92 percent of patients did not use other CAD-related treatments.

For the secondary measures on disease process, patients enrolled experienced a mean increase in hemoglobin level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment timepoint from the mean baseline level of 8.6 g/dL. The mean reduction in bilirubin levels was by -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.

In the CARDINAL study, the most common adverse reactions occurring in 10 percent or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 13 percent of patients who received Enjaymo. These serious adverse reactions were streptococcal sepsis and staphylococcal wound infection, arthralgia, and respiratory tract infection. None of the adverse reactions led to discontinuation of Enjaymo in the study. Dosage interruptions due to an adverse reaction occurred in 17 percent of patients who received Enjaymo.

Following the completion of the 26-week treatment period of CARDINAL (Part A), eligible patients continued to receive Enjaymo in an extension study.

“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD,” said Catherine Broome, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, and a principal investigator in the CARDINAL study. “For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients.”

The approval comes more than a year after Sanofi’s first submission for approval was rejected by the FDA due to manufacturing issues. Sanofi gained the drug through its acquisition of Bioverativ in 2018.

The recommended dose of Enjaymo is based on body weight and is administered intravenously weekly for the first two weeks with administration every two weeks thereafter. Sanofi has priced it at $1,800 per vial.

Enjaymo received FDA Breakthrough Therapy and Orphan Drug designations, and priority review, which is reserved for medicines that, if approved, would represent significant improvements in safety or efficacy in treating serious conditions. Outside the United States, sutimlimab has been submitted to regulatory authorities in Europe and Japan and reviews are ongoing.

Author: Rare Daily Staff