FDA Approves Extended-Release Ruxolitinib Once-Daily for MPNs and GVHD

The FDA approved ruxolitinib extended-release tablets (Jakafi XR) for the treatment of adults with intermediate- or high-risk myelofibrosis (MF), adults with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea (Hydrea), and adults and children aged 12 years and older with steroid-refractory acute or chronic graft-versus-host disease (GVHD) after failure of 1 or 2 lines of systemic therapy, manufacturer Incyte announced.¹

The approval adds a once-daily formulation to the established ruxolitinib formulation given twice daily. Jakafi XR is expected to be available for pharmacy orders by May 8, 2026.

“Patients living with chronic conditions like MPNs [myeloproliferative neoplasms] and GVHD often struggle with managing complex treatment regimens or have multiple conditions,” Naveen Pemmaraju, MD, Professor of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, stated in the news release. “Since its initial approval in 2011, ruxolitinib has helped transform the treatment landscape for patients with MPNs and GVHD. With the approval of Jakafi XR, appropriate patients now have the choice of a single daily tablet.”

Basis for Approval

FDA approval was supported by an open-label, randomized, 2-period, 2-way crossover bioequivalence study conducted in healthy adults (NCT06555081).² A total of 169 participants were included in the pharmacokinetic analysis, randomly assigned 1:1 to receive either ruxolitinib immediate-release (IR) 25 mg twice daily followed by ruxolitinib extended-release (XR) 55 mg once daily, or the reverse sequence, with a 7-day washout between periods.

Steady state was reached by day 2 of multiple dosing for both formulations. The XR formulation demonstrated prolonged absorption, with a median time to maximum concentration of 3.0 hours vs 2.0 hours for IR, and an extended mean half-life of 5.4 vs 3.0 hours, respectively. Geometric mean ratios for the primary bioequivalence parameters: area under the concentration-time curve from 0 to 24 hours (AUC_0-24h,ss), minimum observed steady-state concentration (C_min,ss), and observed concentration at 24 hours (C_24h,obs,ss), all fell within the prespecified 0.80 to 1.25 bioequivalence range.

With the extended-release design, peak concentration (C_max,ss) was approximately 25% lower with XR than IR, a finding the investigators characterized as consistent with the pharmacokinetic profile of the formulation. Fewer patients reported treatment-emergent adverse events with XR than IR (11.8% vs 20.2%), with similar safety profiles between the formulations.

Clinical Context

Ruxolitinib, a first-in-class JAK1/JAK2 inhibitor first approved by the FDA in 2011, has become a foundational treatment across MF, PV, and GVHD.¹ In MF, the drug addresses a rare myeloproliferative neoplasm characterized by bone marrow fibrosis, progressive cytopenias, and splenomegaly. In PV, it is indicated for patients with inadequate response to or intolerance of hydroxyurea, the conventional cytoreductive agent in that setting. In acute and chronic GVHD, a potentially life-threatening immune complication of allogeneic stem cell transplantation affecting multiple organ systems including skin, gastrointestinal tract, and liver, ruxolitinib is indicated for steroid-refractory disease, a population with historically limited therapeutic options.

Dosing, Administration, and Safety

Jakafi XR is administered as a single oral tablet once daily, with or without food, and must be swallowed whole without splitting, crushing, or chewing. The FDA has not approved Jakafi XR for MF or PV in pediatric patients; its pediatric indication is limited to GVHD in patients aged 12 years and older.

The known adverse event profile of ruxolitinib applies to Jakafi XR. Clinically significant risks include myelosuppression; thrombocytopenia, anemia, and leukopenia are among the most common hematologic findings. Other risks include serious infection and potential disease worsening upon abrupt discontinuation. Class-related risks include nonmelanoma skin cancers, hyperlipidemia, and, based on experience with other JAK inhibitors, increased risk of major cardiovascular events, thromboembolic disease, and secondary malignancies, particularly in current or former smokers.

REFERENCES

1. Incyte announces FDA approval of Jakafi XR (ruxolitinib) extended-release tablets for the treatment of myelofibrosis, polycythemia vera and graft-versus-host disease. News release. Incyte. May 1, 2026. Accessed May 4, 2026. https://tinyurl.com/47znhmd8

2. Gong X, Xun Z, Getsy J, McGee R, Mondick J, Punwani N. Bioequivalence of ruxolitinib once-daily extended-release vs twice-daily immediate-release tablets in healthy adults. Blood. 2025;146(suppl 1):5045. doi:10.1182/blood-2025-5045