FDA Approves Imaavy (Nipocalimab-aahu), First Drug for Warm Autoimmune Hemolytic Anemia

The U.S. Food and Drug Administration (FDA) has approved Imaavy (nipocalimab-aahu) injection for warm autoimmune hemolytic anemia (wAIHA) in adult and pediatric patients 12 years of age and older currently or previously treated with corticosteroids. Approved on August 24, Imaavy is the first FDA-approved treatment for this serious condition, and the approval marks the first time a therapy has been proven safe and effective specifically for wAIHA.

wAIHA is a rare blood disorder where the immune system mistakenly attacks and destroys the body's own red blood cells — a process called hemolysis. This destruction happens faster than the body can replace the red blood cells, leading to a shortage of healthy red blood cells (anemia). Normally, red blood cells live about 120 days and deliver oxygen throughout the body. In wAIHA, a type of antibody called immunoglobulin G (IgG) mistakenly tags red blood cells for destruction by immune cells. The disease is called "warm" because this process occurs at normal body temperature. wAIHA is the most common type of autoimmune hemolytic anemia, affecting approximately 1 to 3 per 100,000 people per year and can occur at any age. The disease is characterized by significant fatigue, dizziness, palpitations, and shortness of breath, and may result in potentially life-threatening complications such as thromboembolism. Imaavy is a selective FcRn blocker, designed to reduce circulating IgG autoantibodies while preserving B-cell function.

FDA based its approval on results from the wAIHA Study (NCT04119050), a 24-week, randomized, double-blind, placebo-controlled clinical trial. The study enrolled patients with a confirmed wAIHA diagnosis of at least 3 months who had low hemoglobin levels (below 10 g/dL), evidence of active red blood cell destruction (hemolysis), and a positive direct antiglobulin test (DAT) — a blood test that detects antibodies attacking red blood cells. All patients had previously received or were currently receiving treatment for wAIHA, reflecting a population with a significant unmet medical need. In this study, 118 patients were randomly assigned to one of three treatment groups: Imaavy 30 mg/kg given by IV infusion once every 4 weeks; Imaavy 15 mg/kg given by IV infusion once every 2 weeks; or placebo (an inactive treatment). Patients were allowed to remain on stable doses of other medications they had been taking for wAIHA.

A key measure of effectiveness was whether patients achieved a durable hemoglobin response — a meaningful and sustained improvement in red blood cell levels. The proportion of patients with a durable hemoglobin response was 24% in the Imaavy 30 mg/kg arm compared to 8% in the placebo arm. The 15 mg/kg arm did not lead to a higher proportion of patients with a durable hemoglobin response compared to placebo. The primary endpoint was defined stringently: hemoglobin at or above 10 g/dL and at least a 2 g/dL increase from baseline sustained for 28 or more days, achieved by Week 16, without rescue therapy. A mean 1 g/dL hemoglobin increase appeared at Week 1 in the Imaavy arm, with a median time to first response of 4.1 weeks versus 12.1 weeks for placebo. On the fatigue side, the 3.5-point FACIT-Fatigue advantage over placebo at Week 24 landed with a 95% confidence interval of 0.64 to 6.39, a key secondary endpoint that the trial's statistical plan labels descriptive.

The most common adverse reactions in patients with wAIHA treated with Imaavy were peripheral edema (swelling of the lower legs, ankles, feet caused by a build-up of fluid in body tissues), fatigue, diarrhea and fever. Other side effects are infusion-related reactions, including headache, influenza-like illness, rash, nausea, dizziness, chills, and erythema (redness of the skin). At the approved 30 mg/kg intravenous every-four-weeks dose, peripheral edema, diarrhea, and fever each occurred in at least 10% of patients. The safety profile is consistent with Imaavy's established record in generalized myasthenia gravis, where it received FDA approval in April 2025. The ENERGY open-label extension is ongoing.

FDA granted Imaavy Fast Track, priority review, and orphan designations for this indication. Approval was granted to Janssen Biotech, Inc.

The FDA has also granted Breakthrough Therapy designation to rilzabrutinib for the treatment of wAIHA. The designation is supported by data from the ongoing, open-label, phase 2b LUMINA 2 study (ClinicalTrials.gov Identifier: NCT05002777), which evaluated the efficacy, safety, and pharmacokinetics of rilzabrutinib, an oral, reversible Bruton tyrosine kinase inhibitor, in patients with wAIHA. Findings showed treatment with rilzabrutinib led to durable hemoglobin response, which was sustained with long-term follow-up. Based on these results, Sanofi initiated the phase 3 LUMINA 3 trial (ClinicalTrials.gov Identifier: NCT07086976), which is investigating rilzabrutinib vs placebo in adults with wAIHA. The primary outcome measure of the study is the proportion of patients achieving durable hemoglobin response, defined as an increase of hemoglobin by at least 2 g/dL from baseline on at least two thirds of evaluable scheduled visits between week 12 and week 24 in the absence of rescue medication and transfusion. Rilzabrutinib is currently approved under the brand name Wayrilz for the treatment of adults with persistent or chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. Sanofi's rilzabrutinib was also designated an orphan drug in Japan for the treatment of wAIHA.