The FDA noted that additional requirements are needed prior to the approval of ruxolitinib extended-release for patients with myelofibrosis, polycythemia vera, and graft-versus-host disease, in a complete response letter.
The FDA has issued a complete response letter for ruxolitinib (Jakafi) extended-release (XR) tablets for once-daily use for the treatment of certain types of myelofibrosis, polycythemia vera, and graft-versus-host disease (GVHD).
In the complete response letter, the FDA stated that they cannot approve the application in its present form. While the FDA acknowledged that the study submitted in the new drug application (NDA) for the agent met its objective of bioequivalence based on area under the curve (AUC) parameters, there were additional requirements needed for approval.
Following the issue, Incyte plans to meet and work closely with the FDA to determine appropriate next steps.
"An extended-release would help mitigate patient’s risk, and increase compliance by being a once daily medication vs a twice daily medication. The FDA issued a complete response letter, which means that they have looked at the application that considered it and are not going to approve the application. [Incyte] does have the option to resubmit, so it's not dead in the water, but at least with the data that was presented so far, they either need to generate new data, or reformulate the data that was submitted in order to get the application approved, or go a different avenue for regulatory approval," Aaron T. Gerds, MD, MS, assistant professor in Medicine (Hematology and Medical Oncology) at the Cleveland Clinic, told Targeted OncologyTM.
The NDA for ruxolitinib XR tablets was based on 2 studies that were designed to show that dosage strength is proportional and bioequivalent ruxolitinib tablets. In the first study, investigators sought to find the relative bioavailability of ruxolitinib XR tablets to ruxolitinib tablets. They also looked to see whether ruxolitinib XR tablets are dosage strength proportional to ruxolitinib tablets.
In the second, open-label, randomized, 2-period, 2-way crossover study, 63 healthy adults were included to assess the bioequivalence of the highest strength of ruxolitinib XR tablets at a dose of 50 mg given once-daily, compared with the highest strength of ruxolitinib tablets given twice-daily at a dose of 25 mg, following a single dose and at steady-state.
In this study, ruxolitinib XR at 50 mg tablets dosed once a day was shown to be bioequivalent with ruxolitinib 25 mg tablets dosed 2 times a day, based on AUC parameters.
"It depends on what was in the letter, the specifics to why the application was denied, but the next steps would be to take a look at what that feedback was, and try to formulate a strategy to overcome it by providing the data that the FDA is requesting in order to approve it," added Gerds.
Ruxolitinib is a JAK1/JAK2 inhibitor that currently has gained FDA approvals for adult patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea, patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis in adults, adult and pediatric patients aged 12 years and older with steroid-refractory acute GVHD, and adult or pediatric patients 12 years of age or older with chronic GVHD after failure of 1-2 lines of systemic therapy.
“While we are disappointed that the FDA issued a complete response letter for ruxolitinib extended-release tablets, we remain committed to advancing care for people with myeloproliferative neoplasms and GVHD,” said Hervé Hoppenot, chief executive officer of Incyte, in a press release. “We will work closely with the FDA on the appropriate next steps to address their comments.”