Celgene's Inrebic Receives FDA Approval, Breaking the 10-Year Monopoly in Myelofibrosis Treatment
Inrebic's FDA Approval: A New Option After a Decade
Celgene's Inrebic (fedratinib), a JAK2 and FLT3 selective inhibitor, received FDA approval on August 16, 2019, for the treatment of intermediate-2 and high-risk myelofibrosis. This marked the first new drug in approximately 10 years since Incyte's Jakafi (ruxolitinib) dominated the market, representing a significant turning point for patients. This approval (NDA 212327) followed a Priority Review and Orphan Drug Designation, and was completed without an Advisory Committee meeting.
Demonstrated Efficacy Through the JAKARTA Trial
The clinical basis for Inrebic is the global Phase 3 JAKARTA study, which involved 289 patients who had not previously received JAK inhibitor therapy. In this trial, 37% of patients in the 400mg Inrebic group achieved a spleen volume reduction of 35% or more at week 24, demonstrating statistically significant results compared to the control group (1%). Additionally, the proportion of patients with a 50% or greater improvement in total symptom score was 40%, significantly higher than the control group (9%).
Stringent Safety Verification and Black Box Warning
Following a successful approval, Inrebic faced a clinical hold by the FDA in 2013 due to reports of Wernicke's Encephalopathy during clinical trials. Subsequently, Impact Biomedicines demonstrated safety data, and the clinical hold was lifted in 2017. As a result, Inrebic includes a Black Box Warning in its prescribing information regarding the risk of serious encephalopathy, and mandatory thiamine (vitamin B1) level testing before and after administration.
The Outcome of a $7 Billion Deal and Market Competition
This approval represents a key achievement in Celgene's pipeline, secured through the acquisition of Impact Biomedicines for a total of $7 billion in 2018. In the market dominated by Jakafi, with annual sales exceeding $3 billion, Inrebic is expanding its reach not only as a first-line treatment but also as a second-line treatment for patients who have failed Jakafi. With Bristol Myers Squibb (BMS) completing the acquisition of Celgene, this drug will further strengthen BMS's hematologic oncology portfolio and directly benefit from its extensive commercialization network.
The approval of Inrebic is a significant commercial milestone as it breaks the 10-year monopoly of Jakafi in the $3 billion myelofibrosis market and establishes a new competitive landscape. The 37% spleen volume reduction rate observed in the Phase 3 JAKARTA trial is clinically meaningful; however, the Black Box Warning related to Wernicke's Encephalopathy and mandatory thiamine monitoring may pose limitations to initial prescription uptake. In the medium to long term, Inrebic is expected to secure a dominant position in the late-stage market with high unmet needs based on the results of the JAKARTA2 trial in patients who have failed Jakafi therapy. Bristol Myers Squibb (BMS), which acquired Celgene, will solidify its revenue model in the hematologic oncology pipeline by actively pursuing the achievement of milestones and sales milestones, totaling up to $5.9 billion of the $7 billion acquisition price.
Source: openFDA (api_fda)
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA212327