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.
"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," Tsutomu Nakagawa, president and chief executive officer of SMPA, said in the release. "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. We are committed to working closely with the FDA to progress the clinical development of nuvisertib and bring an alternative treatment option to patients with myelofibrosis."
What is Nuvisertib and Myelofibrosis?
Nuvisertib is an oral investigational selective inhibitor of PIM1 kinase that has shown potential antitumor and antifibrotic activity through multiple pathways, including triggering cancer cell death in preclinical models. It was observed to inhibit cell growth and increase cancer cell death in mouse and human blood cells with the JAK2 V617F mutation, which is commonly seen in myelofibrosis.
In laboratory models of myelofibrosis, nuvisertib alone or with ruxolitinib (Jakafi) normalized white blood cell and neutrophil counts and reduced spleen size and bone marrow scarring, as per the release. The safety and effectiveness of nuvisertib are now being studied in an early-stage clinical trial for patients with intermediate- and high-risk myelofibrosis.
The FDA granted nuvisertib orphan drug designation for myelofibrosis in 2022, and Japan’s Ministry of Health, Labour and Welfare did the same in 2024.
Myelofibrosis, a rare blood cancer, leads to scar tissue buildup in the bone marrow because of abnormal signaling in the Janus-associated kinase pathway, according to the release. This can cause an enlarged spleen, severe symptoms and low hemoglobin or platelet levels. Myelofibrosis affects about 1 in 500,000 people worldwide.
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