Ianalumab Enhances Treatment Outcomes for Immune Thrombocytopenia Patients

Patients with immune thrombocytopenia (ITP) experienced longer periods without treatment failure when treated with the investigational drug ianalumab alongside standard therapy. This promising finding was presented at the 67th American Society of Hematology (ASH) Annual Meeting and published in the journal Blood. The study marks a significant advancement as it is the first to test this novel therapy early in the disease course.

Dr. Hanny Al-Samkari, the lead author and the Peggy S. Blitz Endowed Chair in Hematology/Oncology at Mass General Brigham Cancer Institute, stressed the importance of the findings. “In patients for whom first-line therapy had stopped working, treatment with four once-monthly infusions of ianalumab provided long-term disease control with no need for chronic therapy and no increase in infection risk,” he stated.

ITP is an autoimmune disorder where the immune system destroys platelets, essential for blood clotting. Normal platelet counts range from 150,000 to 400,000 per microliter of blood; however, patients with ITP often have counts below 50,000. The condition affects an estimated 50,000 individuals in the United States, with women being more frequently impacted than men.

Current first-line treatments typically involve steroid medications, which can lead to adverse side effects like obesity, cataracts, and loss of bone density. Dr. Al-Samkari highlighted the growing challenge in treating ITP, noting, “The longer people have ITP, the more difficult it becomes to treat. One of the major unmet needs in ITP treatment is a therapy that truly changes the course of the disease.”

Ianalumab’s Mechanism and Study Design

Ianalumab works by targeting B cells, which are white blood cells that mistakenly attack the body. By inhibiting the signals necessary for B cell activation and growth, the drug helps eliminate these harmful cells and prevents the formation of new ones.

The VAYHIT2 trial was a Phase III randomized controlled study conducted across the United States and 23 other countries. It included 152 patients with ITP who had either not responded to or relapsed after standard first-line treatment. Approximately two-thirds of participants were women, all of whom presented with a platelet count below 30,000 at the start of the study.

Each patient received eltrombopag, a once-daily oral medication approved by the U.S. Food and Drug Administration for ITP, for a duration of 16 to 24 weeks. Participants were then randomly assigned to receive either four once-monthly infusions of a lower dose of ianalumab (3 mg per kilogram), a higher dose (9 mg per kilogram), or a placebo.

The primary endpoint of the study was the time to treatment failure, defined as the duration until patients experienced a bleeding episode requiring immediate treatment or needed another ITP therapy after stopping the study drug. The key secondary endpoint assessed stable response rates at six months, defined as maintaining platelet counts above 50,000 without additional treatment.

Results and Implications

The median follow-up was 12.9 months for the higher-dose ianalumab group, 13.6 months for the lower-dose group, and 11.6 months for the placebo group. Results indicated that the time to treatment failure was 13 months for patients receiving the higher dose of ianalumab, while it was “not estimable” for the lower dose, compared to 4.7 months for the placebo group.

Dr. Al-Samkari explained that “not estimable” signifies that not enough patients in the lower-dose group experienced significant bleeding episodes to calculate the duration until treatment failure accurately. Furthermore, 62% of patients on the higher dose and 56.9% on the lower dose achieved a stable response at six months, compared to 39.2% among those on placebo.

Patients treated with ianalumab also reported reduced fatigue levels, the second most common symptom of ITP after bleeding, according to quality of life assessments. Though higher rates of transient neutropenia were observed in the ianalumab groups, this condition typically resolved quickly. Importantly, infection rates did not differ significantly compared to the placebo group, nor were the infections more severe.

While the study presents compelling results, it does have limitations. As participants had only received one prior treatment for ITP, the findings do not clarify whether ianalumab would be effective for patients with multiple previous treatments. Additionally, the current follow-up period is insufficient to determine the long-term impact of ianalumab on disease progression.

Dr. Al-Samkari noted that follow-up will continue for up to 39 months to evaluate the durability of ianalumab treatment. Another clinical trial, VAYHIT1, is underway to assess ianalumab combined with steroids in previously untreated ITP patients, which will also be published in The New England Journal of Medicine.

These developments represent a significant step forward in the treatment of immune thrombocytopenia, potentially providing patients with a new option that could alter the course of their disease.