Patients with immune thrombocytopenia (ITP) who received ianalumab (previously known as VAY736), a first-in-class investigational drug being developed by Novartis, in addition to standard therapy went longer without a bleeding episode that needed urgent treatment or needing another treatment for their ITP, compared with patients who received a placebo in addition to standard therapy.
The study, funded by Novartis, the developer of ianalumab, is the first to test a novel drug for ITP early in the disease course.
The study results were presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition held December 6 – 9, 2025, in Orlando, Florida.[1] The study results were simultaneously published online in The New England Journal of Medicine. [2]
“In patients for whom first-line therapy had stopped working, treatment with four once-monthly infusions of ianalumab on top of standard therapy provided long-term disease control with no need for chronic therapy and no increase in infection risk,” explained lead study author Hanny Al-Samkari, MD, the Peggy S. Blitz Endowed Chair in Hematology/ Oncology at Mass General Brigham Cancer Institute and an associate professor of medicine at Harvard Medical School, both in Boston.
ITP is an autoimmune disease in which the immune system mistakenly destroys platelets, cells that help promote blood clotting. A normal platelet count is between 150,000 and 400,000 per microliter of blood; in patients with ITP, it’s often less than 50,000. The disease is rare, affecting an estimated 50,000 people in the United States — women more frequently than men.
Standard first-line treatment includes steroid medications with or without antibody infusions. However, long-term steroid use can cause side effects such as obesity, cataracts, and loss of bone density.
“The longer people have ITP, the more difficult it becomes to treat,” Al-Samkari said.
“One of the major unmet needs in ITP treatment is a therapy that truly changes the course of the disease,” he added.
Mechanism of Action
Ianalumab is a novel, first-in-class monoclonal antibody which binds to and blocks
B cells (white blood cells in the immune system) and B-cell activating factor (BAFF-) receptor, which are key in the pathophysiology of immune thrombocytopenia (ITP) .
When B cells overreact they mistakenly attack the patient’s own body and blocking signals that these B cells need to grow and activate, the drug helps rid the body of the problematic cells and prevent new ones from developing by causing enhanced depletion of B cells via antibody-dependent cellular toxicity (ADCC) and inhibition of B-cell activation, maturation, proliferation, and survival.
Study design
The VAYHIT2 study (NCT05653219) was a phase 3 randomized controlled trial conducted in the United States and 23 other countries. The trial enrolled 152 patients with ITP who had either not responded to or relapsed after standard first-line treatment (50 patients were randomized to ianalumab 9mg/kg, 51 to ianalumab 3mg/kg, and 51 to placebo).
About two-thirds of the patients were women. All patients had a platelet count of less than 30,000 at study entry.
Combination
Eltrombopag (Promacta®; Novartis)* is a once-daily pill approved by the U.S. Food and Drug Administration to treat ITP after first-line treatment has failed. It works by stimulating the bone marrow to produce more platelets. Each participating patient received eltrombopag for 16 to 24 weeks. In addition, patients were randomly assigned to receive four once-monthly infusions of a lower dose of ianalumab (3 mg per kilogram of body weight), a higher dose ianalumab (9 mg per kilogram), or a placebo.
The study’s primary endpoint was time to treatment failure (TTF), defined as elapsed time until patients had a bleeding episode necessitating ‘rescue therapy‘ (rapid-acting treatment with steroids or antibodies) or a new ITP treatment after discontinuing study therapy.
The key secondary endpoint was stable response at six months, defined as at least 75% of platelet counts between weeks 19 and 25 measuring higher than 50,000 with no rescue therapy or new ITP treatment.
The median follow-up was 12.9 (8.6–18.0) months for the higher-dose ianalumab group, 13.6 (8.4–18.1) months in the lower-dose group, and 11.6 (8.1–18.2) months in the placebo group. The study results showed that the time to treatment failure (TTF) was significantly longer for patients treated with ianalumab 9mg/kg (HR 0.55, 95% CI 0.32–0.92; log-rank p=0.021) and ianalumab 3mg/kg (HR 0.58, 95% CI 0.34–0.98; log-rank p=0.023), vs placebo; median (95% CI). For patients on the higher dose of ianalumab the TTF was 13 (5.1–not estimable) months, and ‘not estimable‘ for patients on the lower dose (3.7–NE), compared with 4.7 (3.9–5.6) months for those in the placebo group, respectively.
“‘Not estimable’ means that the number of patients in the lower-dose group who had problematic bleeding episodes or other primary endpoint events was too small to calculate the time to treatment failure,” Al-Samkari explained.
Sixty-two percent of patients on the higher dose of ianalumab and 56.9% of those on the lower dose achieved a stable response at six months, compared with 39.2% of those who received the placebo.
At 24 weeks, patients in both ianalumab groups reported lower scores for fatigue, the second most common symptom of ITP after bleeding, on a quality of life questionnaire, compared with those in the placebo group. Patients treated with ianalumab had higher rates of transient neutropenia (below-normal levels of a type of white blood cell that helps the body fight infection) than those in the placebo group. This neutropenia generally resolved within a few days. However, they did not contract infections at higher rates than those in the placebo group, nor were the infections contracted any worse in severity than patients in the placebo group.
Study limitation
One limitation of the study is that, because patients had received just one prior treatment for ITP, the results shed no light on whether ianalumab treatment would increase time to treatment failure for patients with multiple prior treatments. Additionally, patient follow-up is not yet long enough to show whether ianalumab treatment actually halts long-term disease progression. “We will follow the patients for 39 months to look at the long-term durability of ianalumab treatment,” Al-Samkari said.
A randomized trial of ianalumab plus steroids or placebo in previously untreated patients with ITP, known as VAYHIT1 (NCT05653349), is now underway.
__
Note: * Eltrombopag is a prescription medicine used to treat adults and children 1 year and older with low blood platelet counts due to persistent or chronic immune thrombocytopenia (ITP) when other medicines to treat your ITP or surgery to remove the spleen have not worked well enough. Eltrombopag is used to try to raise platelet counts in order to lower your risk for bleeding.
Clinical trials
A Study of Efficacy and Safety of Ianalumab Versus Placebo in Addition to Eltrombopag in Primary Immune Thrombocytopenia Patients Who Failed Steroids (VAYHIT2) – ClinicalTrials.gov ID NCT05653219
Study of Ianalumab Versus Placebo in Addition to First-line Corticosteroids in Primary Immune Thrombocytopenia (ITP) (VAYHIT1) – ClinicalTrials.gov ID NCT05653349
Highlights of prescribing information
Eltrombopag (Promacta®; Novartis)[Prescribing Information]
Reference
[1] Al-Samkari H, Cuker A, Zaja F, Michel M, Ghanima W, Stauch T, Zhang L, Hou M, Zander T, Sharif A, Sun J, Kumar Nath U, Schutgens R, Rossi E, Deleu L, Červinek L, Yoon JH, Chang H, Ruchutrakool T, Iino M, Goto T, Urban P, Fronczek J, Foster M, Weill M, Cooper N. Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment. 67th ASH® / American Society of Hematology Annual Meeting. Abstract LBA-2 [Abstract]
[2] Cuker A, Stauch T, Cooper N, Al-Samkari H, Michel M, Ghanima W, Urban P, Fronczek J, Foster M, Weill M, Zhang L, Hou M, Zander T, Sharif A, Sun J, Nath UK, Schutgens R, Rossi E, Deleu L, Červinek L, Yoon JH, Chang H, Ruchutrakool T, Iino M, Goto T, Zaja F; VAYHIT2 Investigators. Ianalumab plus Eltrombopag in Immune Thrombocytopenia. N Engl J Med. 2025 Dec 9. doi: 10.1056/NEJMoa2515168. Epub ahead of print. PMID: 41363800.
Featured image courtesy © 2019 – 2025 ASH/Nick Agro. Used with permission.
DOI
 who received ianalumab (previously known as VAY736), a first-in-class investigational drug being developed by Novartis, in addition to standard therapy went longer without a bleeding episode that needed urgent treatment or needing another treatment for their ITP, compared with patients who received a placebo in addition to standard therapy.){kind=link}