Enjaymo (sutimlimab-jome)

Enjaymo (sutimlimab-jome), previously known as BIVV009 or TNT009, is an antibody-based therapy first developed by Bioverativ. The company and its assets were acquired in 2018 by Sanofi, which continues to develop and market the treatment.

The therapy was approved by the U.S. Food and Drug Administration (FDA) in February 2022 to reduce hemolysis, or red blood cell destruction, in adults with cold agglutinin disease (CAD), becoming the first approved therapy for this rare condition.

Europe and Japan are considering whether to approve the therapy for the same indication.

How does Enjaymo work?

Enjaymo is a lab-made monoclonal antibody that works by selectively blocking C1 protein activity. C1 plays a central role in the classical complement pathway, which is overly active in CAD, leading to hemolysis and anemia, or low red blood cell counts, which is responsible for most of the disease’s symptoms.

The complement system is a set of more than 30 blood proteins, mainly produced by the liver, that contribute to the body’s natural immune defenses. By suppressing only one of its pathways, Enjaymo ensures that the complement system is not completely inactive.

The therapy, which is administered directly into the bloodstream, is expected to prevent chronic hemolysis, increase hemoglobin levels, and reduce or prevent the need for blood transfusions — reducing patients’ symptoms and disease burden and improving their quality of life.

Hemoglobin is the protein responsible for transporting oxygen in red blood cells.

Enjaymo in clinical trials

The safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of Enjaymo were first investigated in 122 healthy volunteers and adults with complement-pathway-related diseases, including CAD, in a Phase 1 trial (NCT02502903). Pharmacokinetics refers to the therapy’s movement into, through, and out of the body, while pharmacodynamics assesses its effects on the body.

Enjaymo’s favorable safety profile and biological effects in CAD patients — including its suppression of the classical complement pathway, increase in hemoglobin levels, and improvement of hemolysis biomarkers — led to beginning two Phase 3 trials.

The open-label, two-part, Phase 3 CARDINAL study (NCT03347396) evaluated the safety and effectiveness of Enjaymo in 24 adults with primary CAD who received at least one blood transfusion within six months of enrolling.

Participants received weight-based doses of the therapy once a week for the first two weeks, then every other week for another 24 weeks, totaling about six months of treatment.

Results from the study’s Part A showed that 54% of patients met the main goal of reaching target hemoglobin levels or showing a target level rise after six months, while not requiring blood transfusions after week 5 of the study. The therapy was generally safe.

Enjaymo also reduced patient hospitalizations more than threefold, and the number of blood transfusions by 75%.

In Part B, the therapy was associated with a sustained normalizing of the levels of hemoglobin and bilirubin — a marker of hemolysis. Quality of life improvements also were sustained over one year of treatment; 86.4% of patients remained transfusion-free from six months to a year.

The two-part, placebo-controlled, Phase 3 CADENZA trial (NCT03347422) tested Enjaymo in 42 adult CAD patients with no recent history of a blood transfusion. Participants were assigned randomly to receive either the therapy, at the same regimen as in CARDINAL, or a placebo for six months (Part A), after which all received the therapy for an additional year (Part B).

Part A results showed the therapy was superior to a placebo at increasing hemoglobin levels, reducing the need for blood transfusions, and lowering the several hemolysis biomarker levels. It also resulted in greater improvements in quality of life and reduced anemia symptoms, such as weakness, shortness of breath, heart palpitations, and chest pain, compared with a placebo.

Other details

Enjaymo is approved by the FDA at a recommended dose of 6,500 mg for people weighing 39 to 75 kg (about 86–165 lbs), and 7,500 mg for those weighing more than 75 kg. After once-a-week infusions for the first two weeks, it should be given every other week.

The most common side effects associated with Enjaymo include respiratory tract infection, viral infection, diarrhea, indigestion, cough, joint pain, arthritis, and swelling.

It is contraindicated, or not recommended, to people with known allergies to sutimlimab-jome, or any of Enjaymo’s inactive components.

Enjaymo also may increase patients’ susceptibility to developing serious infections, including those caused by certain types of bacteria known as encapsulated bacteria. For this reason, patients should be vaccinated against encapsulated bacteria before starting Enjaymo and be regularly monitored for any signs of infection.

Enjaymo may increase a patient’s risk of developing autoimmune diseases, such as systemic lupus erythematosus. For this reason, those taking Enjaymo should be monitored regularly for signs or symptoms of an autoimmune condition and treated accordingly.

Once treatment ends, patients should be monitored closely for any signs or symptoms of hemolysis. Physicians may consider restarting Enjaymo if these indications are present immediately after treatment is discontinued.

 

Last updated: Feb. 18, 2022, by Marta Figueiredo PhD

 


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