FDA Clears Once-Daily Ruxolitinib Tablets for Myelofibrosis, Polycythemia Vera, and GVHD

The FDA has approved ruxolitinib extended-release tablets (Jakafi XR) for use in select patients with myelofibrosis, polycythemia vera (PV), and graft-vs-host disease (GVHD).

The specific indications are as follows:

• Adults with intermediate- or high-risk myelofibrosis;
• Adults with PV who experienced an inadequate response to or are intolerant of hydroxyurea;
• Adults and children at least 12 years of age with steroid-refractory acute graft-vs-host disease (GVHD) or chronic GVHD after one or two lines of systemic therapy have failed.

The regulatory decision was supported by findings from a clinical study showing that the once-daily 55-mg ruxolitinib tablet was bioequivalent to the immediate-release, twice-daily 25-mg ruxolitinib tablet. According to the announcement from Incyte, the drug developer, the extended-release tablet delivers the same active ingredient at comparable levels throughout the day, which suggests potential for comparable clinical benefit.

It was noted that the toxicity profile of Jakafi XR was aligned with that of the immediate-release formulation. Across the ruxolitinib clinical program, the most common adverse effects reported with the agent include low platelet count, low red blood cell (RBC) count, and infections in those with chronic GVHD; low platelet counts, low red or white blood cell counts, infections, and swelling in those with acute GVHD; and low platelet count, low red blood cell count, bruising, dizziness, headache, and diarrhea in those with myelofibrosis or PV.

“Patients living with chronic conditions like [myeloproliferative neoplasms] and GVHD often struggle with managing complex treatment regimens or have multiple conditions,” Naveen Pemmaraju, MD, professor of leukemia in the 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.”

What is the regulatory history of immediate-release ruxolitinib?

In November 2011, ruxolitinib was first approved for use in patients with intermediate- and high-risk myelofibrosis based on findings from two phase 3 studies (Study 1, NCT00952289; Study 2, NCT00934544), which showed that the agent led to a reduction in spleen size.^2,3 In Study 1, 42% of patients with myelofibrosis achieved at least a 35% reduction from baseline in spleen volume at week 24 with ruxolitinib (n = 155) vs <1% of those given placebo (n = 154; P < .0001); in study 2, these respective rates were 29% and 0% (P < .0001). Indications included primary myelofibrosis, post-PV myelofibrosis, and post–essential thrombocythemia MF.

In December 2014, the regulatory agency cleared ruxolitinib for patients with PV who were resistant or intolerant to hydroxyurea.⁴ The decision was supported by data from the phase 3 RESPONSE trial (NCT01243944), which showed that 60% of patients who received the JAK1/2 inhibitor (n = 110) achieved hematocrit control without phlebotomy vs 20% of those given best available therapy (BAT; n = 112).⁵

Subsequently, in May 2019, the FDA approved ruxolitinib for use in adult and pediatric patients aged 12 years and older with steroid-refractory acute GVHD based on findings from the phase 2 REACH1 trial (NCT02953678).⁶ When ruxolitinib was paired with corticosteroids (n = 49), it induced an overall response rate (ORR) of 57% at day 28, with a complete response (CR) rate of 31%.

In September 2021, the regulatory agency approved ruxolitinib for the treatment of adult and pediatric patients at least 12 years of age with chronic GVHD after 1 or 2 lines of systemic therapy had failed.⁷ The decision followed data from the phase 3 REACH3 trial (NCT03112603) in which the agent (n = 165) elicited an ORR of 70% (95% CI, 63%-77%) at day 1 of cycle 7 vs 57% (95% CI, 49%-65%) with BAT (n = 164); the respective CR rates in these arms were 8% and 5%, and the respective partial response rates were 62% and 52%.⁸

What’s next for Jakafi XR?

According to Incyte, Jakafi XR will be ready for pharmacy orders by May 8, 2026.¹

“The approval of Jakafi XR reinforces Incyte’s leadership in hematology and our focus on meeting the evolving needs of patients with myeloproliferative neoplasms (MPNs) and GVHD,” Bill Meury, chief executive officer at Incyte, stated in a news release. “Jakafi XR offers appropriate patients and physicians a once-daily option, expanding choice without changing the well-established role of Jakafi in clinical practice.”

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 1, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-jakafi-xrtm-ruxolitinib-extended
2. November 2011, ruxolitinib was first approved for use in patients with intermediate- and high-risk myelofibrosis. Clin Cancer Res. 2012;18(12):3212-3217. doi:10.1158/1078-0432.CCR-12-0653
3. Jakafi. Prescribing information. Icyte; 2026. Accessed May 1, 2026. https://www.incytepicentral.com/sites/g/files/hssmmz4016/files/2026-05/Jakafi-Prescribing-Information-01May26.pdf#page=1
4. FDA approves Jakafi (ruxolitinib) for the treatment of patients with uncontrolled polycythemia vera. News release. Incyte. December 4, 2014. Accessed May 1, 2025. https://investor.incyte.com/news-releases/news-release-details/fda-approves-jakafir-ruxolitinib-treatment-patients-uncontrolled
5. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426-435. doi:10.1056/NEJMoa1409002
6. FDA approves Jakafi (ruxolitinib) for the treatment of patients with acute graft-versus-host disease. News release. Incyte. May 24, 2019. Accessed May 1, 2026. https://investor.incyte.com/news-releases/news-release-details/fda-approves-jakafir-ruxolitinib-treatment-patients-acute-graft
7. Incyte announces FDA approval of Jakafi (ruxolitinib) for treatment of chronic graft-versus-host disease (GVHD). News release. Incyte. September 22, 2021. Accessed May 1, 2026. https://bwnews.pr/3m5XRTJ
8. Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228-238. doi:10.1056/NEJMoa2033122