Platelet-boosting treatment curbs bleeding for ITP patients

Oral hetrombopag safely boosts platelet counts and reduces bleeding and the need for rescue therapy in adults with persistent immune thrombocytopenia (ITP) who have symptoms lasting three to 12 months after diagnosis.

That’s according to an analysis of data from a Phase 3 clinical trial (NCT03222843), which found comparable outcomes for ITP patients with chronic disease, or those with symptoms lasting more than a year.

“Hetrombopag showed [a] favorable [safety] and efficacy profile in patients with persistent ITP, aligning with results observed in chronic ITP and overall ITP patients,” the researchers wrote in the study, “Hetrombopag for Patients with Persistent Primary Immune Thrombocytopenia: A Post-hoc Analysis of A multicenter, Randomized Phase Ⅲ Trial,” published in Research and Practice in Thrombosis and Haemostasis.

ITP is an autoimmune disorder in which the immune system attacks platelets — cell fragments produced in the bone marrow that are essential for blood clotting. Such attacks reduce platelet counts, a condition called thrombocytopenia which boosts the risk of bruising, bleeding, and other symptoms.

Hetrombopag works by activating the thrombopoietin receptor, thereby stimulating the bone marrow to produce more platelets. It’s approved in China under the brand name Hengqu as a second-line treatment for primary ITP. The therapy’s approval was supported by data from a Phase 3 clinical trial, which enrolled 424 adults with primary ITP diagnosed at least six months prior.

Most patients in trial respond to treatment

Most patients in the trial had chronic ITP (81%), meaning ongoing symptoms for more than 12 months after diagnosis, while the remaining 19% had persistent ITP, or symptoms persisting for three to 12 months beyond diagnosis. Patients were randomly assigned to one of two daily hetrombopag doses (2.5 and 5 mg) or placebo for eight weeks.

The proportion of patients who responded — defined as a rise in platelet count to at least 50×10⁹/L — was markedly higher in patients treated with hetrombopag than in those given a placebo. Hetrombopag also outperformed the placebo in reducing the risk of bleeds and the need for rescue treatments.

The researchers used data from the Phase 3 study to compare outcomes among patients with persistent ITP, those with chronic ITP, and the overall population.

According to the analysis, the proportion of participants who responded to eight weeks of hetrombopag treatment was similar between the persistent and chronic ITP groups, at 2.5 mg (68.8% vs. 56.6%) and at 5 mg (74.3% vs. 61.8%). In comparison, the response rate in the overall population was 58.9% for the 2.5 mg dose and 64.3% for the 5 mg dose.

These findings illustrate “the stable and predictable efficacy across different disease stages of ITP,” the researchers wrote.

Persistent ITP patients who received the higher, 5 mg dose of hetrombopag responded faster than those who received the lower, 2.5 mg dose (median eight days vs. 21 days). Similar results were seen in the chronic and overall ITP groups (median 14 days vs. 21 days).

Fewer persistent ITP patients treated with hetrombopag required rescue therapy with 2.5 mg (12.5%) and 5 mg (8.6%) than the placebo group (30.8%). Likewise, fewer persistent ITP patients had bleeding symptoms at 2.5 mg (65.6%) and 5 mg (45.7%) than placebo (69.2%). Comparable proportions of patients with bleeds and who required rescue therapy were seen in the chronic and overall ITP population.

“These findings illustrated the aligned efficacy of hetrombopag in lowering bleeding risk and minimizing the demand for rescue therapy,” the team wrote.

The median maximum continuous treatment response duration in persistent ITP patients was 17 days with 2.5 mg of hetrombopag and 22 days with 5 mg. This was equivalent to the response in the chronic and overall ITP populations of 22 days at both doses.

The incidence of treatment-related adverse events was consistent across persistent ITP (62.7%), chronic ITP (50.7%), and the overall population (53.1%). Common adverse events included increased platelet counts, elevated blood lactate dehydrogenase levels (a marker of tissue damage), and higher liver enzymes (markers of liver injury).

“The findings preliminarily proved that hetrombopag effectively increased and sustained platelet levels in patients with persistent ITP, with benefits comparable to those observed in chronic and overall ITP populations,” the researchers concluded.