FDA Gives Priority Review to Sutimlimab for Adults with CAD

The U.S. Food and Drug Administration (FDA) is giving priority review to Sanofi’s request that sutimlimab be approved to treat hemolysis in adults with cold agglutinin disease (CAD).

The FDA is expected to announce its decision on or before Nov. 13, as priority review shortens the regulatory process to six months from 10.

If approved, sutimlimab would become the first treatment of hemolysis for adult patients.

Hemolysis refers to the premature breakdown of red blood cells, which transport oxygen throughout the body using the hemoglobin protein. In CAD, hemolysis is caused by the activation of the so-called classical complement pathway, a part of the complement system that promotes immune responses.

Sutimlimab (formerly BIVV009 and TNT009) is an antibody that selectively blocks the activity of a protein called C1s, which has a central role in this pathway.

Sanofi’s request to approve sutimlimab is based on results from the first part of the open-label Phase 3 CARDINAL study (NCT03347396), which enrolled 24 adults with CAD. All had received at least one blood transfusion in the prior six months. Participants were given sutimlimab by intravenous infusion (directly into the bloodstream) every week for the first two weeks, then every other week for another 26 weeks (approximately six months), at doses tailored to an individual’s weight.

The trial’s primary goal was an increase in hemoglobin levels of at least 2 g/dL from baseline (study start), or normalization of hemoglobin levels to at least 12 g/dL without a need for additional transfusions.

Results showed 13 patients met this goal. On average, hemoglobin levels had increased by 2.6 g/dL (from 8.6 to 11.2 g/dL) at the trial’s end.

In addition, 17 people (70.8%) did not require blood transfusions between weeks 5 and 26, and clinically meaningful increases in scores on the Functional Assessment of Chronic Illness Therapy Fatigue Scale, suggesting better quality of life (average increase of 10.9 points), were recorded.

None of the serious adverse events seen in seven participants were deemed related to sutimlimab. One person died of liver cancer, which also considered not related to treatment. Two withdrew from the trial prior to its completion, for reasons unrelated to the therapy.

All 22 people who completed the trial’s first part are now enrolled in its second part, an extension study that aims to evaluate sutimlimab’s safety and tolerability over one year.

“Results from our 26-week pivotal Phase 3 study clearly demonstrated that sutimlimab had a clinically meaningful effect on complement-mediated hemolysis, which is the cause of anemia and fatigue,” John Reed, MD, PhD, the global head of research and development at Sanofi, said in a press release.

“If approved, sutimlimab will be the first and only FDA-approved treatment to uniquely address C1-activated hemolysis and help alleviate the chronic disease burden for people with CAD,” he added.

Sanofi is currently conducting a separate Phase 3 trial, called Cadenza, (NCT03347422) to assess treatment with sutimlimab in 40 CAD patients who did not undergo a recent blood transfusion. Top-line results are expected by December 2021.

The FDA granted breakthrough therapy and orphan drug designations to sutimlimab.