Sutimlimab induces rapid responses in cold agglutinin disease

Sutimlimab appeared to be a safe and effective treatment for patients with cold agglutinin disease, according to results of a first-in-human clinical trial of the anti-C1s monoclonal antibody published in Blood.

“The drug was well tolerated, produced clinically meaningful increases in hemoglobin levels and precluded the need for transfusions, even in patients for whom multiple prior therapies had failed,” Bernd Jilma, MD, senior study author and professor in the department of clinical pharmacology at the Medical University of Vienna, said in a press release.

Cold agglutinin disease is an autoimmune hemolytic anemia that affects about 10,000 people a year in the U.S. and Europe. There currently is no FDA-approved treatment for the disease; however, the anti-CD20 antibody rituximab (Rituxan; Genentech, Biogen) has been used with limited success.

The phase 1b component of the randomized, prospective trial included 10 patients (age range, 56-76 years; 80% women) with cold agglutinin disease who had a median disease duration of 5 years (range, 1-20 years). Patients received 10 mg/kg sutimlimab (BIVV009, Bioverativ) as a test dose, followed by 60 mg/kg between 1 and 4 days later, and three additional weekly doses of 60 mg/kg.

Median hemoglobin increased by 1.6 g/dL within the first week (P = .007), with a median best response after 6 weeks of a 3.9-g/dL increase (interquartile range, 1.3-4.5; 95% CI, 2.1-4.5).

Hemoglobin levels increased by more than 2 g/dL in seven of 10 patients, including some who failed to respond to or relapsed after treatment with rituximab, rituximab in combination with bendamustine, or eculizumab (Soliris, Alexion).

Hemoglobin increased by at least 4 g/dL in five patients and normalized to at least 12 g/dL in four patients.

Reticulocyte counts increased by a median 41% within the first 24 hours (P = .0381) among all patients and then declined as hemoglobin levels rose.

Haptoglobin levels normalized in four patients and lactate levels normalized in five patients within the first 2 weeks.

Median bilirubin levels — which were abnormal in eight of 10 patients at baseline — decreased by 61% to a normalized level within 24 hours of the first sutimlimab infusion.

Six patients who were dependent on blood transfusions did not need one for up to 18 months while on sutimlimab.

Patients experienced recurrence of hemolytic anemia about 3 to 4 weeks after the last dose of sutimlimab, but the effects reversed after treatment resumed.

Three patients treated with sutimlimab did not respond sufficiently (0.5-1.3 g/dL increase in hemoglobin). Two of those had active lymphoma with lymphocytic bone marrow infiltrates of 15% and 70%.

Researchers observed no serious adverse events related to sutimlimab.

Limitations of the trial included the lack of patient information on recent bone marrow histology as well as missing mutation analyses for MYD88. Researchers noted that further testing is needed in a larger multicenter, multinational trial.

Sutimlimab has been granted breakthrough therapy designation by the FDA and is being evaluated in phase 3 trials to determine its safety and efficacy in patients with cold agglutinin disease.

“Provided that safety results remain positive, sutimlimab could become the first approved treatment for cold agglutinin disease,” Jilma said in a press release. “The drug clearly addresses an unmet medical need, as we have seen rapid, strong responses in patients for whom multiple prior therapies have failed.” – by John DeRosier

Disclosures : True North Therapeutics Inc. funded this study. Jilma reports travel expenses from True North Therapeutics. Please see the study for all other authors’ relevant financial disclosures.