Novel CD38 treatment option for ITP appears promising

Coagulation

By Mardi Chapman

8 Jul 2024

Mezagitamab, a fully human immunoglobulin IgG1 monoclonal antibody with high affinity for CD38 expressing cells, has been shown to deliver a rapid and sustained improvement in platelet response in patients with chronic/persistent immune thrombocytopenia (ITP).

Interim results from a phase 2 study presented in the Late Breakthrough Session at the ISTH 2024 Congress, showed the monoclonal antibody was tolerable with the incidence of TEAEs similar between the treated and control groups.

Professor David Kuter, from Massachusetts General Hospital and Harvard Medical School, said that by targeting plasmablasts, plasma cells and natural killer cells, mezagitamab should deplete anti-platelet antibodies that cause increased platelet clearance and inhibit platelet production from megakaryocytes.

“Although patients do respond to many standard therapies, a good proportion, maybe 20% or more, fail to attain an adequate plate account and have a need for additional therapies,” he said.

The small phase 2 study enrolled 41 adult patients with persistent ITP and a platelet count ≤30,000/uL. The cohort had a mean disease duration of 11 years and were highly pretreated with a mean 3.9 prior ITP treatments.

The study compared mezagitamab at doses of 100 mg, 300 mg, and 600 mg and a combined group versus a placebo group

It found any TEAEs were similar in both the combined group receiving mezagitamab and the controls (68% v 69%) as were any TEAEs related to the drug (32% v 39%).

Serious adverse events and TEAS leading to hospitalisation were both seen in 14% of the intervention group compared to 7.7% in controls, and there were no deaths.

Professor Kuter said that the drug was tolerable and had a favourable safety profile compared with a placebo.

Regarding efficacy endpoints, the analysis found mezagitamab led to improvements in platelet response, complete platelet response, clinically meaningful platelet response and haemostatic platelet count.

“And there are two important messages from this study: all three treatment arms had a rise in platelet counts that occurred significantly within the first week or two of study. This drug seemed to work rather rapidly in these patient groups.”

“And more importantly, there was a dose response in terms of the platelet count elevation…with the highest dose resulting in the highest platelet count and with that platelet response being maintained after treatment was discontinued at week eight,” Professor Kuter said.

The study found fewer patients with ≥1 bleeding events in the mezagitamab group compared to controls (17.9% v 46.2%).

“And again, those who got the highest dose of 600 mg had no bleeding event.”

The study was sponsored by Takeda.

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