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In an interview with Pharmacy Times®, Firas El Chaer, MD, hematologist at the University of Virginia, discusses an abstract he worked on and presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.
The abstract centered on nuvisertib (TP-3654), an investigational selective PIM1 kinase inhibitor, and its efficacy in patients with relapsed or refractory (R/R) myelofibrosis. El Chaer and his investigators found that nuvisertib led to durable clinical response and sustained hematologic improvement in patients enrolled in the trial. El Chaer discusses the clinical implications of these results for pharmacists and patients with myelofibrosis seeking new, effective treatment options.
Pharmacy Times: Could you elaborate on the unique mechanism of action of TP-3654 and how it contributes to its efficacy in myelofibrosis, particularly in comparison to traditional treatment regimens?
1. TP-3654 (nuvisertib) is a PIM kinase inhibitor targeting PIM1 and JAK-STAT pathways, offering a novel treatment approach for myelofibrosis.
2. Nuvisertib shows promise in relapsed/refractory cases, with fewer side effects like anemia or thrombocytopenia, making it ideal for combination therapies.
3. Studies are now evaluating TP-3654 in combination with ruxolitinib or momelotinib, with early results expected in 1-2 years.
Firas El Chaer: TP-3654, or nuvisertib, is a novel PIM kinase inhibitor. It's a drug that specifically targets PIM1 kinase. It is a novel mechanism of action that relies on the Janus kinase (JAK)-STAT pathways, in addition to many other pathways that control cytokines, providing additional treatment options for the patients.
Pharmacy Times: What are the potential clinical implications of these findings for patients with myelofibrosis?
El Chaer: In the United States, there are currently 4 JAK inhibitors approved for the treatment of myelofibrosis. Despite all of that, many of our patients unfortunately have their disease progressing and evolving into a higher-risk disease, and unfortunately, succumbing to their disease. Having another option with a novel mechanism of action is very important, especially in the relapsed/refractory phase. Another important benefit of this drug is that it is not associated with major cytopenia, such as anemia or thrombocytopenia. It would be a great product to combine with other molecules, other JAK inhibitors, other drugs, to treat myelofibrosis, providing additional treatment benefit for our patients.
Pharmacy Times: Given the promising results of this monotherapy study, what are the next steps for development of TP-3654?
The 66th ASH Annual Meeting and Exposition took place from Saturday, December 7 to Tuesday, December 10 in San Diego, California. You can read our coverage here.
El Chaer: As I presented, there were 74 patients on the monotherapy arm. Currently the study started additional arms combining this drug, nuvisertib, with ruxolitinib (Jakafi; Incyte Corporation, Novartis) or momelotinib (Ojjaara; GSK). Currently, those 2 arms are enrolling. It's still very early in the enrollment stages. So hopefully, in the next year or two, we will see much data about these combinations.
