FDA Approves First Treatment for Warm Autoimmune Hemolytic Anemia

The US Food and Drug Administration (FDA) approved nipocalimab-aahu (IMAAVY) as the first-ever treatment for warm autoimmune hemolytic anemia (wAIHA). The approval covers adults and pediatric patients ≥ 12 years of age who are currently or previously treated with corticosteroids.

Nipocalimab-aahu, an immunoselective neonatal Fc receptor (FcRn) blocker developed by Johnson & Johnson, is designed to target and reduce pathogenic immunoglobulin G (IgG) autoantibodies while preserving B-cell function.

The approval follows FDA Priority Review and marks the first therapy proven safe and effective specifically for wAIHA, a rare, life-threatening condition in which autoantibodies attach to and destroy red blood cells, leading to severe anemia and debilitating fatigue.

"The Phase 2/3 ENERGY study demonstrates that targeting pathogenic IgG can meaningfully change the treatment paradigm for wAIHA," David Kuter, MD, DPhil, Distinguished Physician at Massachusetts General Hospital and professor of medicine at Harvard Medical School, said in a statement. "More patients treated with nipocalimab-aahu achieved a durable hemoglobin response compared with placebo, meaning their red blood cell levels went up and stayed up. For patients, this approval means that they now have a therapy with a proven safety profile that targets the disease-driving autoantibodies in wAIHA."

An Underserved Population With No Approved Options

wAIHA affects approximately 1 to 3 new people per 100,000 annually, with about 1 in 8,000 individuals living with the condition. Incidence increases after age 50, and the disease carries an increased risk of complications including venous thrombotic events, acute renal failure, and infection.

Previously, available treatment options included only corticosteroids and immunosuppressants, therapies that suppress the immune system broadly rather than targeting the IgG autoantibodies that drive the disease.

Trial Design Behind the Approval

The approval is based on findings from ENERGY (NCT04119050), a multicenter, randomized, double-blind, placebo-controlled Phase 2/3 study evaluating nipocalimab against placebo in adults with wAIHA, followed by an open-label extension period. The trial randomized 115 adults in an approximately 1:1:1 ratio to 2 nipocalimab dose schedules or placebo. After 24 weeks of double-blind treatment, patients could enter an open-label extension period to receive nipocalimab for 144 weeks, followed by a 6-week follow-up period.

The primary endpoint was durable hemoglobin response, defined as hemoglobin concentration ≥ 10 g/dL and an increase from baseline of ≥ 2 g/dL sustained for at least 28 days, without need for rescue therapy.

Durable Hemoglobin Response and Reduced Fatigue

Findings from the ENERGY study suggest that durable hemoglobin response, the primary endpoint, was achieved by 23.7% of patients in the approved 30 mg/kg intravenous dose given every 4 weeks and 21.1% of patients in a 15 mg/kg dose given every 2 weeks, compared with 7.7% of patients on placebo. The result for the approved dose reached statistical significance within the study's prespecified hierarchical testing procedure (one-sided P = .015); the result for the alternate dose schedule did not meet significance under the same procedure (P = .044) and is considered nominal.

Patients in the approved-dose group showed a mean increase in hemoglobin of ≥ 1 g/dL as early as week 1, an effect that was maintained through week 24. Among responders, the median time to first hemoglobin response was 4.1 weeks (range, 1 to 12) in the nipocalimab-aahu group compared with 12.1 weeks (range, 4 to 16) in the placebo group; per the study's prespecified analysis plan, this timing data is considered descriptive rather than confirmatory.

The trial also required participants who achieved durable hemoglobin response to begin tapering their corticosteroid dose, reduced by 10% of the baseline dose every 2 weeks provided hemoglobin did not decline by ≥ 1 g/dL. By week 24, the mean reduction in corticosteroid dose from baseline was 15% in the approved-dose nipocalimab group compared with 4% in the placebo group, a prespecified endpoint within the hierarchical testing procedure.

Nipocalimab-aahu was also associated with a 3.5 point greater mean improvement in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score versus placebo at week 24, a key secondary endpoint, with a mean difference of 3.51 points (95% CI, 0.64 to 6.39) and higher scores indicating less fatigue; this result carried a nominal one-sided P value under the multiplicity control strategy. Improvement in FACIT-Fatigue score in the nipocalimab-aahu group was observed as early as week 2, though investigators have noted the correlation between hemoglobin improvement and fatigue improvement was only mild to moderate, not complete. Full results of the ENERGY study were presented at the European Hematology Association 2026 meeting in June 2026.

The safety profile observed in wAIHA was consistent with the established safety profile of nipocalimab-aahu in generalized myasthenia gravis (gMG), for which the drug was first approved in April 2025, with no new safety signals identified. The most common adverse reactions (≥ 10%) among patients with wAIHA treated with nipocalimab-aahu were peripheral edema, diarrhea, and pyrexia.

What This Means for Patients

"Living with wAIHA often means relentless fatigue and the constant uncertainty of not knowing what tomorrow will bring," Karen Jones, president and executive director of wAIHA Warriors, said in a statement. "Patients may cycle through periods where they start to feel like themselves again, and then their hemoglobin drops, the exhaustion returns, and they're back to square one. For the first time, our community has a treatment specifically for our disease."

"As the first therapy approved for wAIHA, nipocalimab-aahu has the potential to redefine the management of wAIHA, particularly for those with uncontrolled disease," David M. Lee, MD, PhD, global immunology therapeutic area head at Johnson & Johnson, said in a statement.

Nipocalimab-aahu is supplied as a 300 mg/1.62 mL and a 1200 mg/6.5 mL (185 mg/mL) single-dose vial for intravenous injection. J&J's IMAAVY withMe patient support program offers educational resources, a dedicated nurse navigator, and cost support options regardless of insurance type.

References

1. Johnson & Johnson. FDA approves IMAAVY® (nipocalimab-aahu) as first-ever treatment for warm autoimmune hemolytic anemia (wAIHA), representing a landmark advancement for patients. News release. August 24, 2026. Accessed August 25, 2026. https://www.jnj.com/media-center/press-releases/fda-approves-imaavy-nipocalimab-aahu-as-first-ever-treatment-for-warm-autoimmune-hemolytic-anemia-waiha-representing-a-landmark-advancement-for-patients

2. Johnson & Johnson. IMAAVY® (nipocalimab-aahu) demonstrates durable hemoglobin response and rapid onset of effect in pivotal Phase 2/3 study in warm autoimmune hemolytic anemia (wAIHA), an autoantibody-driven disease with no FDA-approved therapies. News release. June 11, 2026. Accessed August 25, 2026. https://www.jnj.com/media-center/press-releases/imaavy-nipocalimab-aahu-demonstrates-durable-hemoglobin-response-and-rapid-onset-of-effect-in-pivotal-phase-2-3-study-in-warm-autoimmune-hemolytic-anemia-waiha-an-autoantibody-driven-disease-with-no-fda-approved-therapies

3. Fattizzo B, Murakhovskaya I, Ueda Y, et al. Nipocalimab for warm autoimmune hemolytic anemia: results from the Phase 2/3 randomized, double-blind ENERGY study. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden.

4. ClinicalTrials.gov. Efficacy and safety study of nipocalimab in adults with warm autoimmune hemolytic anemia (ENERGY). Identifier: NCT04119050. Updated 2026. Accessed August 25, 2026. https://www.clinicaltrials.gov/study/NCT04119050