The U.S. Food and Drug Administration (FDA) granted fast track designation to nuvisertib (TP-3654) for the treatment of patients with intermediate or high-risk myelofibrosis (MF), according to a news release from Sumitomo Pharma.
Fast track designation by the FDA is given to investigational therapies for serious or life-threatening conditions that have the potential to address unmet medical needs.
In updated preliminary phase 1/2 data, which was presented at the European Hematology Association 2025 Congress in Milan, Italy, nuvisertib demonstrated clinical activity, including symptom and spleen responses that correlated with cytokine modulation.
Glossary:
PIM1 kinase: protein involved in cell survival and growth; targeted by some cancer treatments to slow or stop cancer cell growth.
Cytokine modulation: changes in proteins that regulate immune responses, which can help reduce inflammation or control disease symptoms.
JAK2 V617F mutation: common genetic change in myelofibrosis that causes abnormal cell signaling and contributes to disease progression.
Bone marrow fibrosis: scarring of the bone marrow, which interferes with normal blood cell production.
Preliminary results showed that nuvisertib monotherapy was well tolerated with no dose-limiting toxicities. Among evaluable patients, 22.2% achieved at least a 25% reduction in spleen volume and 44.4% had at least a 50% reduction in total symptom score. Additional findings included improvements in bone marrow fibrosis in 42.9% of patients, hemoglobin improvements in 24%, and platelet count improvements in 26.7%.
"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," Dr. Jatin Shah, chief medical officer of Oncology at Sumitomo Pharma, said in the news release. "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. The FDA fast track designation reinforces the potential of nuvisertib to provide clinical benefits for patients with myelofibrosis, an unmet medical need."
In addition, treatment with nuvisertib also led to significant cytokine modulation, with reductions in pro-inflammatory cytokines such as EN-RAGE and MIP-1β, and increases in anti-inflammatory cytokines such as adiponectin. These changes significantly correlated with symptom and spleen responses.
Preclinical and emerging clinical data support further investigation of nuvisertib in combination with JAK inhibitors for the treatment of patients with myelofibrosis, as per the release.
