Sumitomo Pharma America announced that the U.S. Food and Drug Administration has granted Fast Track Designation to nuvisertib (TP-3654) for treating patients with intermediate or high-risk myelofibrosis. The designation recognizes the investigational PIM1 kinase inhibitor's potential to address unmet medical needs in this rare blood cancer affecting 1 in 500,000 people worldwide.
The FDA Fast Track Designation is reserved for investigational therapies targeting serious or life-threatening conditions that demonstrate potential to fill significant treatment gaps. Nuvisertib, an oral highly selective PIM1 kinase inhibitor, showed clinical activity including symptom and spleen responses correlating with cytokine modulation in updated preliminary Phase 1/2 data presented at the European Hematology Association Congress in Milan, Italy on June 12, 2025.
Clinical Trial Results Show Promise
Updated data from the ongoing Phase 1/2 study in patients with relapsed/refractory myelofibrosis demonstrated encouraging efficacy signals. Nuvisertib monotherapy appeared well tolerated with no dose-limiting toxicities observed. Among evaluable patients, 22.2% achieved ≥25% spleen volume reduction (SVR25) and 44.4% experienced ≥50% reduction in total symptom score (TSS50).
Additional clinical improvements included bone marrow fibrosis improvement in 42.9% of patients, hemoglobin increases in 24% of patients, and platelet count improvements in 26.7% of patients. The treatment demonstrated significant cytokine modulation, reducing pro-inflammatory cytokines such as EN-RAGE and MIP-1β while increasing anti-inflammatory cytokines like adiponectin. This cytokine modulation showed significant correlation (p<0.001) with symptom and spleen responses.
Mechanism and Development Strategy
Myelofibrosis is characterized by fibrous tissue buildup in bone marrow caused by dysregulation in the Janus-associated kinase (JAK) signaling pathway. Clinical manifestations include enlarged spleen, debilitating symptoms, and reduced hemoglobin and platelet counts. Nuvisertib has shown potential antitumor and antifibrotic activity through multiple pathways, including apoptosis induction in preclinical models.
Preclinical studies demonstrated that nuvisertib inhibited proliferation and increased apoptosis in murine and human hematopoietic cells expressing the clinically relevant JAK2 V617F mutation. In JAK2 V617F and MPLW515L murine myelofibrosis models, nuvisertib alone and combined with ruxolitinib normalized white blood cell and neutrophil counts while reducing spleen size and bone marrow fibrosis.
Regulatory Milestones and Future Development
Nuvisertib previously received Orphan Drug Designation from the FDA for myelofibrosis in May 2022 and from Japan's Ministry of Health, Labour and Welfare in November 2024. The current Phase 1/2 study (NCT04176198) continues evaluating safety and efficacy in patients with intermediate and high-risk myelofibrosis.
"This positive momentum for nuvisertib signals strong promise in our pipeline and reflects our dedication to addressing unmet medical needs on behalf of patients with myelofibrosis and their families," said Tsutomu Nakagawa, Ph.D, President and Chief Executive Officer of Sumitomo Pharma America. "Receiving FDA Fast Track Designation for nuvisertib in the treatment of myelofibrosis reinforces our confidence in its potential as a treatment option for patients facing a poor prognosis with limited treatment options."
Dr. Jatin Shah, Chief Medical Officer of Oncology, emphasized the clinical significance: "The data observed to date demonstrate promising clinical activity for nuvisertib and the strong potential for selective PIM1 inhibition to slow the progression of myelofibrosis. Patients with myelofibrosis are in need of new therapeutic approaches, including combination treatment options, that can provide increased and durable response rates with limited hematologic adverse events."
Preclinical and emerging clinical data support developing nuvisertib in combination with JAK inhibitors for myelofibrosis treatment, potentially offering patients enhanced therapeutic options in this challenging disease setting.
