Novartis announced positive top-line results from VAYHIT2, a Phase III trial evaluating ianalumab plus eltrombopag in patients with primary immune thrombocytopenia (ITP) previously treated with corticosteroids. The combination significantly prolonged the time to treatment failure (TTF), the primary endpoint that assesses how long patients maintain safe platelet levels during and after the treatment period, compared to placebo plus eltrombopag.
The results represent a potential breakthrough for patients with this rare autoimmune disorder, where the immune system mistakenly targets and destroys platelets essential for blood clotting. ITP affects patients with symptoms including prolonged bleeding, easy bruising and chronic fatigue, which can significantly impact daily life.
Trial Results Demonstrate Sustained Efficacy
In VAYHIT2, patients treated with ianalumab plus eltrombopag experienced a significantly higher rate of sustained improvements in platelet count at six months, representing the key secondary endpoint of the study. The safety profile of ianalumab remained consistent with previous clinical studies, with no new safety signals identified.
"While current treatments for ITP are generally effective in raising platelet counts, many patients require life-long treatment to maintain safe levels, which can create a lasting treatment burden," said Adam Cuker, M.D., Professor of Medicine and Chief, Section of Hematology, University of Pennsylvania. "The results from VAYHIT2 are encouraging, as they suggest that ianalumab may support longer periods of disease control and reduce the need for continuous treatment."
Addressing Unmet Medical Need
Many people living with ITP cycle through multiple therapies, unable to achieve long-term disease control. Current treatment options often focus on maintaining safe platelet levels and preventing bleeding complications and may require ongoing use. The burden of chronic treatment and unpredictability of relapses can significantly impact quality of life.
"For many people living with ITP, chronic treatment can disrupt their daily life due to the burden of regular dosing, dose adjustments and side effects," said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. "These positive top-line results from the Phase III study highlight the potential of ianalumab, if approved, to deliver long-term disease control with four once-monthly doses and enable extended time off treatment."
Novel Mechanism of Action
Ianalumab (VAY736) is a novel fully human monoclonal antibody being investigated for its potential to treat various B cell-driven autoimmune diseases. Its mechanism of action targets B cells in two ways, combining B cell depletion via antibody-dependent cellular toxicity (ADCC) and interruption of BAFF-R mediated signals of B cell function and survival.
The drug originates from an early collaboration with MorphoSys AG, a company which Novartis later acquired in 2024. In clinical trials, ianalumab has shown promising efficacy and a favorable safety profile in Sjögren's disease, systemic lupus erythematosus, and immune thrombocytopenia.
Trial Design and Regulatory Path
VAYHIT2 (NCT05653219) is a Phase III, multi-center, randomized, double-blind study evaluating the efficacy and safety of two different doses of ianalumab versus placebo, in addition to eltrombopag, in adults with primary ITP (platelet count <30 G/L) who failed previous first-line treatment with corticosteroids. Patients were randomized 1:1:1 to receive four once-monthly intravenous infusions of ianalumab at 3 mg/kg, ianalumab at 9 mg/kg or placebo.
The primary endpoint was time to treatment failure, defined as the time from randomization until either: a platelet count of less than 30 G/L later than 8 weeks from randomization; the need for rescue therapy later than 8 weeks from randomization; initiation of a new ITP treatment at any time; ineligibility or inability to taper/discontinue eltrombopag; or death. The key secondary endpoint is the percentage of patients with a stable platelet count response at Month 6.
Data is expected to be presented at an upcoming medical meeting and included in future regulatory submissions in 2027 along with results from the ongoing first-line ITP trial, VAYHIT1. Ianalumab has been granted Orphan Drug Designation by the US Food and Drug Administration and the European Medicines Agency.
Broader Development Program
Ianalumab is being investigated in other B cell-driven autoimmune diseases, including ongoing Phase III trials in first-line ITP and in second and later lines of warm autoimmune hemolytic anemia, with readouts expected in 2026. The drug is also being studied for potential treatment of Sjögren's disease, systemic lupus erythematosus, lupus nephritis, warm autoimmune hemolytic anemia and diffuse cutaneous systemic sclerosis.
