The full clinical hold implemented by the U.S. Food and Drug Administration (FDA) on all clinical trials conducted under the Investigational New Drug (IND) application for pacritinib was removed and initial data has now been reported as efforts to make this treatment available are ongoing.1
Myelofibrosis is a type of blood cancer known as a myeloproliferative neoplasm (MPN). It involves the abnormal development and function of bone marrow cells that produce blood cells which leads to the formation of scar tissue in the bone marrow. This can cause anemia, enlargement of the spleen and liver, fatigue, and other problems. In some patients with myelofibrosis, the condition progresses to acute myeloid leukemia.
Proteins known as JAK1 and JAK2 may play a role in the development of MPNs, including myelofibrosis, by causing the body to make the wrong number of blood cells. Drugs that suppress JAK1 and JAK2 are used to treat different forms of MPN by reducing the number of abnormal blood cells associated with these disorders. JAK1/JAK2 inhibitors can, however, result in too much suppression of the bone marrow’s production of blood cells. Myelosuppression results in low white blood cell and platelet counts which can negatively impact patient health and quality of life.
Pacritinib is designed to fight myelofibrosis by interfering with the kinases JAK2 and FLT3 to potentially keep tumors from developing. Unlike other JAK inhibitors, pacritinib does not cause myelosuppression, which, if safe and effective, could offer an advantage to patients.
In a pivotal clinical trial, pacritinib was shown to be significantly more effective than the best available therapy in reducing splenomegaly and other symptoms in patients with myelofibrosis and thrombocytopenia. The current study (PERSIST-2) is a follow-up that assessed the use of pacritinib in patients with myelofibrosis and thrombocytopenia.2
In the PERSIST-2 study 311 patients with myelofibrosis whose platelet counts were 100,000/μL or less were treated with either pacritinib or the “best available therapy” and directly compared.
The co-primary endpoints were the percentage of patients who attained both a spleen volume reduction of at least 35% as assessed by imaging and a 50% reduction in symptom burden after 24 weeks of therapy.
Overall, pacritinib led to significant improvements in both endpoints compared with the control group. At week 24 18% of patients receiving pacritinib achieved spleen volume reduction of 35% or more compared to 3% of those treated with “best available therapy”, and 25% of patients receiving pacritinib achieved a reduction in symptom burden of 50% or greater compared with 14% receiving “best available therapy.”
There was no difference in the overall survival between the three groups and the most common side effects from pacritinib were thrombocytopenia and anemia. Perhaps most importantly, the initial concerns regarding excessive mortality due to pacritinib treatment were not observed in the full analysis of mature data, and the survival curves in the three cohorts were not different.