Platelet therapy is often critical to prevent or stop bleeding in patients with immune thrombocytopenic purpura (ITP). Clinical trials presented last month at the 2023 American Society of Hematology (ASH) Annual Meeting in San Diego, California, explored potential new therapies in this area as well as treatment sequencing.
What is ITP?
ITP is a rare disorder where immune system antibodies destroy platelets and inhibit platelet production that can lead to unexpected bleeding in different parts of the body. Corticosteroids that temporarily block the antibodies attacking platelets are the standard first-line treatment for ITP, but they have many side effects and patients often relapse, causing a need for platelet therapy.
“The main manifestation of ITP is a markedly decreased platelet count, and platelets are really responsible for maintaining our natural hemostasis balance. They really control our bleeding tendency and when they get below a certain number, we have a likelihood to have spontaneous bleeding, which of course can be pretty devastating,” said Catherine Broome, MD, professor of medicine at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.
Thrombopoietin receptor agonists that bind to thrombopoietin receptors to increase platelet production are a primary treatment in this area and the U.S. Food and Drug Administration (FDA) has approved three for ITP:
Eltrombopag (Promacta)
Romiplostim (Nplate)
Avatrombopag (Doptelet)
A Study Showed Promise in a Switch to Avatrombopag
Interim analysis of a phase 4 study explored response in patients who switched from eltrombopag or romiplostim to avatrombopag found that median platelet counts were either improved or maintained with the latter treatment over 90 days with higher patient satisfaction (Abstract 2577).
In an initial cohort of 47 patients, 62% switched from eltrombopag and 38% from romiplostim, and the median platelet count rose from 130×109/L at the switch to 161×109/L after 90 days. (A healthy count is generally between 150×109/L and 450×109/L platelets.)
While the final safety findings will be reported when the study is complete, researchers say the findings suggest that patients may experience sustained effectiveness when switching to avatrombopag. The researchers also conducted a Treatment Satisfaction Medication Questionnaire (TSQM) showing improvement across convenience, global satisfaction, effectiveness, and side effects, starting at day 30 after the switch and continuing through day 90 after the study period (Abstract 3954).
“In a population of patients who were generally responding to thrombopoietin receptor agonists prior to a switch to avatrombopag, these findings suggest that that some patients may experience sustained effectiveness paired with enhanced overall treatment satisfaction when switching from eltrombopag or romiplostim but also the old adage needs to be considered: ‘if it ain’t broke, don’t fix it’,” said James Bussel, MD, professor emeritus of pediatrics at Weill Cornell Medicine in New York City.
Another Study Examined Efgartigimod
Dr. Broome was the lead author of the phase 3 ADVANCE IV trial results, which compared efgartigimod (Vyvgart) with a placebo in boosting platelet counts (Abstract 689). Efgartigimod is a new class of medication called a neonatal Fc receptor (FcRn) blocker that was given weekly intravenously in the trial.
“By blocking that receptor with efgartigimod we are able to allow for an increased clearance of a variety of different antibodies, but specifically the antibody that's targeting the platelets,” said Dr. Broome.
Starting at a measurement of seven days after treatment, efgartigimod had a much faster platelet count increase than was seen with placebo. While it is not yet FDA approved, Dr. Broome thinks “it could be a therapeutic intervention that may turn out to be quite important for patients.”
Dr. Bussel noted that only a third of patients (34.9%) responded to efgartigimod, but that the study also said that the time to response was shorter in the patients who did and that “the data suggests efgartigimod is efficacious in ITP, albeit not wonderfully so.”
Rilzabrutinib, “The Next Big Drug”
Howard Liebman, MD, professor of medicine and pathology at the Keck School of Medicine of the University of Southern California in Los Angeles, said he is most excited about the results of a phase 1/2 trial evaluating rilzabrutinib in patients with relapsed ITP which was published in The New England Journal of Medicine and had extended data presented at ASH (Abstract 685).
Rilzabrutinib can reduce platelet destruction as well as the production of antibodies to destroy platelets and results showed that it was effective with manageable adverse events. The phase 3 LUNA 3 trial will evaluate rilzabrutinib in adults and children with chronic ITP and is currently recruiting patients.
“There's a randomized study versus placebo and intervention, so when that comes out, we'll know the impact, but I think that's going to be the next big drug,” said Dr. Liebman.