Mezagitamab boosts platelet counts in adults with chronic ITP in Phase 2 trial
Strongest responses were seen at highest dose tested in the study
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Takeda’s investigational therapy mezagitamab increased platelet counts in adults with persistent or chronic primary immune thrombocytopenia (ITP) in a Phase 2 trial, with responses seen within days of treatment and the strongest results at the highest dose tested, 600 mg.
“This is a novel therapy that works fast and attacks the underlying mechanism of the disease,” David J. Kuter, MD, PhD, a hematologist with Mass General Brigham Cancer Institute and the study’s lead author, said in a press release. “We saw that it can have a rapid effect, normalizing platelet counts in 48 hours and improving quality of life.”
Following these results, a Phase 3 clinical trial (NCT06722235) is underway and recruiting participants at clinical sites worldwide, including in the U.S. and European Union.
“This study was designed as a dose-ranging, proof-of-concept trial. We are now conducting a phase 3 clinical trial of 600-mg dose of mezagitamab with Mass General Brigham Cancer Institute serving as the leading site in North America,” Kuter said.
How mezagitamab targets immune activity in ITP
The Phase 2 trial results were recently published in The New England Journal of Medicine in a study titled, “A Phase 2 Randomized Trial of Mezagitamab in Primary Immune Thrombocytopenia.”
ITP is an autoimmune disorder in which the immune system attacks platelets, the blood cell fragments that help stop bleeding. The disease is marked by increased platelet destruction, which can raise the risk of bruising and bleeding and can also affect daily life through symptoms such as fatigue and anxiety.
While currently available treatments can boost platelet production or dampen the immune attack, about 20% of patients do not get enough benefit from existing therapies.
Mezagitamab, also known as TAK-079, is an experimental antibody given as a subcutaneous, or under-the-skin, injection. It was designed to target CD38, a protein found on plasma cells, a type of immune cell that helps produce the self-reactive antibodies that drive the immune attacks in ITP.
By reducing immune cell populations, the therapy is meant to lower the abnormal immune activity that drives ITP, potentially easing symptoms.
Trial design tested multiple doses against placebo
The Phase 2 trial (NCT04278924) was a multicenter, placebo-controlled study that enrolled 41 adults across sites in Bulgaria, China, Croatia, Greece, Italy, Japan, Slovenia, Spain, and Ukraine.
Participants had ITP for at least three months and low platelet counts at screening. In the first part of the study, patients were randomly assigned to weekly subcutaneous mezagitamab at 100 mg or 300 mg, or a placebo for eight weeks.
After an interim safety review, the trial added a second part in which patients were randomly assigned to receive mezagitamab at 600 mg or placebo. Overall, the placebo group included 13 patients and the mezagitamab groups included 28 patients. The main goal was safety, while a key efficacy goal was platelet response through week 16, or about four months. After this, patients receiving placebo could join an open-label extension to receive mezagitamab.
Results showed that platelet counts rose more in each mezagitamab dose group than in the combined placebo group. Among the 21 responders in the combined mezagitamab groups, platelet responses began as early as two days after the first dose, and the median time to first response was four days.
The clearest efficacy signal was seen with the 600 mg dose: by week 16, 91% of patients in the 600 mg group achieved a platelet response, compared with 23% in the pooled placebo groups.
At that dose, 82% achieved a complete platelet response, meaning their platelet counts reached at least 100,000 per microliter. Another 91% had a clinically meaningful platelet response, or a rise of at least 20,000 platelets per microliter above their starting levels (baseline). All eligible patients on 600 mg mezagitamab also achieved a hemostatic platelet response, meaning platelet levels rose into a range more likely to help prevent bleeding.
Higher dose linked to longer-lasting platelet response
The mean cumulative duration of response through week 16 was 10.6 weeks with 600 mg mezagitamab, versus 1.1 weeks with placebo. In an additional ad hoc analysis after week 24, 64% of patients in the 600 mg group had a durable platelet response, compared with 8% of patients taking placebo.
The researchers also reported clinically meaningful improvements across several quality-of-life measures in mezagitamab-treated patients, while no such improvement was seen with placebo. However, no formal comparisons between groups were planned for these measures.
Overall, adverse events occurred in 68% of mezagitamab-treated patients and 69% of those on placebo, and most were mild or moderate. No dose-dependent safety concerns were identified.
Infection-related side effects were similar between groups. COVID-19 was the most commonly reported infection-related event. The only side effect reported in more than 10% of participants was injection-site hematoma (a closed wound with blood), which was more common with placebo (23% vs. 7%). No new safety signals emerged during the open-label extension.
These findings build on data reported in 2024, which showed rapid and sustained platelet responses through week 16, with the highest response rates at the 600 mg dose.
