The research heralds a new era of hope for patients with primary immune thrombocytopenia

The research heralds a new era of hope for patients with primary immune thrombocytopenia

More than half of patients in a Phase III clinical trial who received a limited duration of treatment with the experimental monoclonal antibody ianalumab for primary immune thrombocytopenia (ITP), an autoimmune disease that can cause life-threatening bleeding, were able to maintain safe platelet counts without major bleeding episodes for at least one year. The results were published today inNew England Journal of Medicineby researchers at the Perelman School of Medicine at the University of Pennsylvania, and presented by staff at the 67th Annual Meeting and Exhibition of the American Society of Hematology (ASH) in Orlando, Florida (LBA-2).

ITP is an autoimmune disease in which the body's immune cells mistakenly attack platelets, the blood cells responsible for clotting. It affects approximately 50,000 people in the United States and can be diagnosed at any age. ITP is associated with abnormal bleeding from the skin and mucous membranes - including nosebleeds, bleeding gums and/or heavy menstruation - which can be serious if platelet counts are particularly low. ITP also contributes to easy bruising and fatigue.

Some patients with ITP do not require treatment, but for patients with low platelet counts or recurrent or severe bleeding, initial treatment includes steroids, which work well in some patients. However, for patients who continue to experience bleeding problems or low platelet counts despite or after tapering steroids, another form of treatment is required. Although there are currently three FDA-approved second-line therapies for ITP, they generally all require lifelong treatment, either in the form of a daily pill or weekly injections, which have their own side effects and cost.

As a hematologist, I am glad that we have effective therapies for ITP, but these are not necessarily ideal for chronic disease management or long-term quality of life. This study shows that a long-lasting and durable response to ITP treatment is possible without the need for ongoing therapy – and that is a huge benefit for patients.”

Adam Cuker, MD, MS, lead author, division chief of hematology and clinical director of the Penn Blood Disorders Center

Stable platelets and successful completion of treatment

In the double-blind, multicenter clinical trial (called the VAYHIT2 trial), 152 adult patients with ITP were randomized into three arms: a higher dose of ianalumab (50 patients), a lower dose of ianalumab (51 patients), or placebo (51 patients). Ianalumab works by targeting the B-cell activating factor (BAFF) receptor, resulting in the depletion of autoreactive B cells, which are responsible for the anti-platelet antibodies that cause ITP. Patients who had already relapsed after taking steroids or whose ITP did not respond to steroid treatment were eligible for the study. Ianalumab was administered intravenously once a month for four months. Since it takes time for the effect to take effect, all patients also received eltrombopag, one of the pills currently approved for second-line therapy. Eltrombopag is usually taken indefinitely but should be tapered and discontinued for this study.

The study measured “time to treatment failure,” defined as low platelet count, need for additional ITP therapy, inability to taper or discontinue eltrombopag, or death. The estimated probability of avoiding treatment failure at 12 months was 54.2 percent in the high-dose arm and 50.5 percent in the low-dose arm, compared to just 30 percent of patients in the placebo arm. Additionally, when platelet counts were measured at six months (two months after the last dose of ianalumab), 62 percent of patients in the high-dose treatment arm had stable platelet counts, compared to only 39.2 percent of patients in the placebo arm.

“A New Era of Hope”

Additional clinical trials for ianalumab are ongoing, including studies in other autoimmune diseases, and it has not yet been approved by the FDA for patients. Researchers will continue to monitor patients in this study to monitor long-term response to treatment.

“We are excited to see whether the treatment-free responses in this study continue,” said Cuker. "Improving the long-term reality of living with ITP is something we haven't thought about before. The goal has always been to improve platelet counts or reduce bleeding risk, but this research ushers in a new era of hope for patients with ITP."

The study was funded by Novartis.

Sources: