EMA Grants Orphan Drug Designation to Nuvisertib for Myelofibrosis

The European Medicines Agency (EMA) has granted orphan drug designation to nuvisertib (TP-3654), a selective, oral PIM1 kinase inhibitor, for the treatment of patients with myelofibrosis.¹

The designation comes 1 month after the FDA granted fast track designation to the agent for the treatment of patients with intermediate- or high-risk myelofibrosis.²

“Following the recent FDA fast track designation, being granted orphan drug designation from European regulators emphasizes the potential of nuvisertib as a future option for patients living with myelofibrosis,” Tsutomu Nakagawa, PhD, president and chief executive officer of SMPA, stated in a news release.¹ “As we pursue our mission of addressing unique and unmet patient needs, we look forward to working with the EMA to advance the clinical development of nuvisertib.”

The agent is currently under evaluation as monotherapy in a global phase 1/2 trial (NCT04176198) in patients with intermediate- and high-risk myelofibrosis.³ Eligible patients had primary, post–polycythemia vera (PV), or post–essential thrombocythemia (ET) myelofibrosis. Patients must have been ineligible or intolerant to JAK inhibitors or had disease that was relapsed or refractory to JAK inhibition.

During phase 1 dose escalation, patients received between 480 mg of once-daily nuvisertib and 1440 mg of twice-daily nuvisertib.

The primary end point was safety and tolerability. Secondary end points included spleen volume reduction (SVR), total symptom score (TSS), overall survival, changes in bone marrow fibrosis, and pharmacokinetics.

A total of 77 patients were enrolled. The median patient age was 71 years (range, 49-85), and most patients were male (53%). Myelofibrosis subtypes were primary (48%), post-PV (35%), or post-ET (17%) myelofibrosis. The DIPSS risk group was intermediate-1 (23%), intermediate-2 (51%), and high (26%). Most patients had received 1 prior JAK inhibitor (65%), although 5% received 0, and 30% received at least 2. The durations of prior JAK inhibition were less than 6 months (13%), between 6 and 12 months (18%), and greater than 12 months (64%).

In findings shared during the 2025 EHA Congress, investigators reported no dose-limiting toxicity. Moreover, the maximum-tolerated dose was not reached. The most common adverse effects (AEs) were diarrhea (grade 1, 53.2%; grade 2, 16.9%; grade 3/4, 5.2%), nausea (grade 1, 40.3%; grade 2, 20.8%; grade 3/4, 1.3%), and vomiting (grade 1, 29.9%; grade 2, 10.4%; grade 3/4, 0%).

With respect to efficacy, the rate of 50% or greater reduction in TSS (TSS50) was 44.4% (n = 8/18), and those with TSS50 showed early and sustained symptom reduction. Additionally, 83.3% (n = 15/18) of patients showed an improvement on the Patient Global Impression of Change scale.

As of the data cutoff, 25 of 77 patients remained on therapy. Reasons for discontinuation included progressive disease or lack of response (n = 19), AEs (n = 10), death unrelated to treatment (n = 4), physician decision (n = 3), patient or other withdrawal (n = 15), and missing data (n = 1).

In terms of hemoglobin and platelet stability, 24% (n = 6) of hemoglobin response–evaluable patients (n = 25) achieved at least a 1.0-g/dL improvement for at least 12 weeks without any red blood cell transfusion. Additionally, 26.7% (n = 8) of platelet response–evaluable patients (n = 30) showed at least a 30 x 10⁹/L improvement for 28 or more days without any platelet transfusion.

Moreover, among 28 patients, 12 (42.9%) showed an improvement by at least 1 grade in bone marrow fibrosis.

“Patients living with incurable blood cancers like myelofibrosis continue to face limited treatment options, particularly in the relapsed or refractory setting,” Francesco Passamonti, MD, head of the Department of Oncology and Hematology-Oncology at the University of Milan, in Italy, added.¹ “The orphan drug designation for nuvisertib underscores its potential and the urgent need for new therapeutic approaches to a difficult to treat disease.”

References

1. Sumitomo Pharma America announces that the European Medicines Agency has granted orphan drug designation to nuvisertib (TP-3654) for the treatment of myelofibrosis. News release. Sumitomo Pharma America, Inc. July 30, 2025. Accessed August 1, 2025. https://news.us.sumitomo-pharma.com/2025-07-30-Sumitomo-Pharma-America-Announces-that-the-European-Medicines-Agency-Has-Granted-Orphan-Drug-Designation-to-Nuvisertib-TP-3654-for-the-Treatment-of-Myelofibrosis
2. Sumitomo Pharma America announces that nuvisertib (TP-3654) has received FDA fast track designation for the treatment of myelofibrosis. News release. Sumitomo Pharma. June 12, 2025. Accessed August 1, 2025. https://news.us.sumitomo-pharma.com/2025-06-12-Sumitomo-Pharma-America-Announces-that-Nuvisertib-TP-3654-Has-Received-FDA-Fast-Track-Designation-for-the-Treatment-of-Myelofibrosis
3. Rein L, El Chaer F, Scandura JM, et al. Preliminary data from phase I/II study of nuvisertib, an oral investigational selective PIM1 inhibitor, showed clinical response correlating with cytokine modulation in patients with myelofibrosis. Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S221.