Credit: Peter Anderson
The US Food and Drug Administration (FDA) is expediting its review of pacritinib, a tyrosine kinase inhibitor with activity against JAK2 and FLT3, by granting the drug fast track designation.
Pacritinib is under review as a treatment for patients with intermediate- and high-risk myelofibrosis (MF), including those with disease-related or treatment-induced thrombocytopenia and those who cannot tolerate or do not respond well to other JAK2 therapy.
The FDA’s fast track process is designed to expedite the review of drugs to treat serious conditions and fill an unmet medical need.
The program enables a company—in this case, CTI BioPharma—to submit sections of a new drug application on a rolling basis as data becomes available.
That way, the FDA can review sections of the application as they are received, rather than waiting until every section of the application is completed before the entire application can be reviewed. This often leads to faster approval.
Pacritinib is currently under investigation in two phase 3 clinical trials, known as the PERSIST program, for patients with MF.
One of these trials, known as PERSIST-1, includes a broad set of patients without limitations on platelet counts. The other, PERSIST-2, includes patients with low platelet counts.
PERSIST-1
In July 2014, CTI Biopharma completed enrollment in the PERSIST-1 trial, which was designed to enroll approximately 320 patients.
This randomized trial was designed to compared the efficacy and safety of pacritinib with that of best available therapy, other than JAK inhibitors, in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF, without exclusion for low platelet counts.
The primary endpoint is the percentage of patients achieving at least a 35% reduction in spleen volume, measured by MRI or CT from baseline to 24 weeks of treatment.
PERSIST-2
In March 2014, CTI announced the initiation of the PERSIST-2 trial, a comparison of pacritinib and best available therapy, including approved JAK2 inhibitors that are dosed according to product label, in patients with MF whose platelet counts are 100,000/uL or lower.
The trial is designed to enroll up to 300 patients in North America, Europe, Australia, and New Zealand. In October 2013, CTI reached agreement with the FDA on a special protocol assessment for the trial, a written agreement between CTI and the FDA regarding the planned design, endpoints, and statistical analysis approach of the trial to be used in support of a potential new drug application.
Under the special protocol assessment, the trial will have two primary endpoints. The first is the percentage of patients achieving a 35% or greater reduction in spleen volume, measured by MRI or CT scan from baseline to 24 weeks of treatment.
The second primary endpoint is the percentage of patients achieving a total symptom score reduction of 50% or greater using 6 key symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment (MPN-SAF TSS 2.0) diary from baseline to 24 weeks.
More details on the PERSIST-1 and PERSIST-2 trials can be found at www.clinicaltrials.gov.
