Celgene Corporation and Impact Biomedicines today announced the signing of a definitive agreement in which Celgene will acquire Impact Biomedicines, which is developing fedratinib for myelofibrosis and polycythemia vera. Under the terms of the agreement, Celgene will pay approximately $1.1 billion upfront and up to $1.25 billion in contingent payments based on regulatory approval milestones for myelofibrosis. Additional future payments for regulatory approvals in additional indications and sales-based milestones are also possible.

Fedratinib, a highly selective JAK2 kinase inhibitor, was evaluated in 877 patients across 18 clinical trials. In a randomized, placebo-controlled, phase III pivotal trial (JAKARTA-1) for patients with treatment-naïve myelofibrosis, fedratinib demonstrated statistically significant improvements in the primary and secondary endpoints of splenic response and total symptom score, respectively. In an exploratory subgroup analysis, these improvements were observed regardless of a patient’s baseline platelet count.

A multi-center, single-arm phase II trial (JAKARTA-2) evaluated fedratinib in myelofibrosis patients who were found to be resistant or intolerant to ruxolitinib (Jakafi), a JAK1/JAK2 inhibitor. In this second-line setting, fedratinib demonstrated clinically meaningful improvements in splenic response and total symptom score.

As previously reported, JAKARTA-2 was stopped prematurely due to a clinical hold placed on the fedratinib program by the U.S. Food and Drug Administration (FDA) after potential cases of Wernicke’s encephalopathy (WE) were reported in eight out of 877 patients receiving one or more doses (less than one percent of treated patients). The FDA removed the clinical hold in August 2017.

Based on the reported benefit risk profile of fedratinib from the JAKARTA-1 and JAKARTA-2 clinical trials, regulatory applications in myelofibrosis are planned beginning in the middle of 2018.

“Myelofibrosis is a disease with high unmet medical need as the number of patients who are ineligible for or become resistant to existing therapy continues to increase,” said Nadim Ahmed, president of hematology and oncology for Celgene. “We believe fedratinib is uniquely positioned as a potential treatment for myelofibrosis and it provides strategic options for us to build leadership in this disease with luspatercept and other pipeline assets.”

John Hood, chief executive officer, Impact, “We launched Impact Biomedicines and based on our thorough review of the data, fedratinib presents a compelling risk benefit profile in both treatment-naïve patients and patients who are resistant or intolerant to other JAK2 therapies. We believe Celgene is the ideal organization to follow through on our mission of maximizing fedratinib’s potential for patients with myelofibrosis.”

Under the terms of the agreement, Celgene will make an upfront cash payment of approximately $1.1 billion. In addition, Impact Biomedicines’ shareholders are eligible to receive contingent payments based on regulatory approval and sales-based milestones. The maximum aggregate amount payable for regulatory approval milestones is $1.4 billion relating to approvals for myelofibrosis and other indications. Starting from global annual net sales of $1.0 billion, aggregate tiered sales-based milestone payments could total a maximum of $4.5 billion if global annual net sales exceed $5.0 billion.