FDA Issues Says It Won’t Approve Incyte’s Ruxolitinib Extended Release Tablets to Treat Rare Blood Disorders

Rare Daily Staff

The U.S. Food and Drug Administration has issued to Incyte a complete response letter for ruxolitinib extended-release tablets, a JAK1/JAK2 inhibitor, for once-daily use in the treatment of certain types of myelofibrosis, polycythemia vera, and graft-versus-host disease.

The complete response letter states that the FDA cannot approve the application in its present form. The FDA acknowledged that the study submitted in the New Drug Application met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval. Incyte intends to meet with the FDA to determine appropriate next steps.

“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, CEO of Incyte. “We will work closely with the FDA on the appropriate next steps to address their comments.”

The NDA was based on two studies designed to show that ruxolitinib XR tablets are dosage strength proportional and bioequivalent to Jakafi (ruxolitinib) tablets. The first study was designed to determine the relative bioavailability of ruxolitinib XR tablets to Jakafi tablets and to demonstrate that ruxolitinib XR tablets are dosage strength proportional to Jakafi tablets. The second study was an open-label, randomized, two-period, two-way crossover study in 63 healthy adults evaluating the bioequivalence of the highest strength of ruxolitinib XR tablets (50 mg) dosed once-daily (QD) to the highest strength of Jakafi tablets (25 mg) dosed twice-daily (BID), following a single dose and at steady-state. Study results demonstrated that ruxolitinib XR 50 mg tablets dosed QD is bioequivalent to Jakafi 25 mg tablets dosed BID, based on AUC parameters.

Jakafi is a JAK1/JAK2 inhibitor approved by the FDA for treatment of polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF in adults; steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Polycythemia vera (PV) is a rare blood cancer caused by a mutation in stem cells in the bone marrow, resulting in the overproduction of blood cells that puts a person at risk for serious health problems, including blood clots, stroke, and heart attack. Most cases are caused by a JAK2V617F mutation and, without proper management, this debilitating cancer can progress into myelofibrosis and malignancies, including acute myeloid leukemia.

Myelofibrosis (MF) is a rare blood cancer, part of a group of diseases known as myeloproliferative neoplasms. In MF, scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells. This can result in an enlarged spleen, and symptoms such as fatigue, itching, and night sweats. GVHD is a condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) in which the donated cells initiate an immune response and attack the transplant recipient’s organs. There are two major forms of GVHD: acute, which generally occurs within 100 days of transplant, and chronic, which generally occurs more than 100 days after transplant. Both forms are associated with significant morbidity and mortality and can affect multiple organ systems.

Photo: Hervé Hoppenot, CEO of Incyte