Myelofibrosis and the Janus Kinase Inhibitor landscape in 2024

The Janus Kinase-STAT pathway which regulates growth factor and cytokine mediated proliferation is overactivated in Myelofibrosis. JAK Inhibitors (JAKi) work by suppressing the STAT proteins that stimulate JAK, leading to less cell proliferation and lower cytokine mediated symptoms in the patient. There are currently four JAKi approved by the FDA for treatment of Myelofibrosis.

·        Pacritinib (Vonjo® by CTI/SOBI AB) is FDA label indicated for Intermediate or High-Risk primary and secondary Myelofibrosis with platelets < 50x10(9)/L , dosed at 200mg orally twice daily and supplied in 100mg capsules.

·        Fedratinib (Inrebic® by Impact Biomedicines/Celgene) is FDA label indicated for Intermediate or High-Risk primary and secondary Myelofibrosis, dosed at 400mg orally once daily and supplied in 100mg capsules.

·        Momelotinib (Ojjaara® by GlaxoSmithKline) is FDA label indicated for Intermediate or High-Risk primary and secondary Myelofibrosis with anemia, dosed at 200mg orally once daily, supplied in 100mg, 150mg, and 200mg tablets.

·        Ruxolitinib (Jakafi® by Incyte and Jakavi® by Novartis) is FDA label indicated for Intermediate or High-Risk Myelofibrosis, dosed at 20mg orally twice daily initially and supplied as 5mg, 10mg, 15mg, 20mg, and 25mg tablets.

The National Comprehensive Cancer Network (NCCN) has recently updated their evidence-based recommendations in January of 2024 for management of myelofibrosis associated with anemia. Due to the high rates of co-existing anemias in myelofibrosis patients this is an impact population that can be market driving. Current NCCN guidelines in this space now recommend that patient with anemia AND presence of symptomatic splenomegaly that is uncontrolled, then momelotinib is the preferred agent to be used, with pacritinib or Ruxolitinib+Luspatercept+ESA being 2B category alternatives. In patients with anemia and symptomatic splenomegaly currently controlled on a JAKi then Ruxolitinib+Luspatercept+ESA can be used, a cutout of alternative use of momelotinib or pacritinib can be considered useful in certain circumstances in that space. In those patients without symptomatic splenomegaly then the alternative recommendations are Ruxolitinib+Luspatercept+ESA or momelotinib or pacritinib.

This is an interesting position for momelotinib to have in the treatment paradigm as it is the newest JAKi to the myelofibrosis market (less than a year) and currently occupies a preferred recommendation for symptomatic anemia patients currently uncontrolled under a JAKi. This distinction may help drive increased utilization, overcoming potential slow uptake by providers for newer release medication in a populated class. Momelotinib’s specific cutout may also help maintain market access via payor restriction due to it comparatively high price vs its in-class peers, currently Ojjaara® utilizes two different specialty pharmacies for distribution which is on par for Inrebic® and Vonjo®, but pales in comparison with the seven specialty pharmacies that have access to dispense Jakafi®.

Expanded growth in areas with limited treatment options are extremely welcome for many prescribers. The current changes in treatment access will lie in the potential restriction of certain medications behind step edits by PBM’s, intentioned indication spaces are essential to maintain access in these situations. A welcome perspective in the space will be upcoming comparative efficacy studies done by non-affiliated treatment centers to show real world evidence in myelofibrosis.

National Comprehensive Cancer Network. (2024). Myeloproliferative Neoplasms (version 1.2024). Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf

Product Information: Inrebic oral capsules, fedratinib oral capsules. Celgene Corporation (per FDA), Summit, NJ, 2019.

Product Information: JAKAFI oral tablets, ruxolitinib oral tablets. Incyte Corporation (per manufacturer), Wilmington, DE, 2021.

Product Information: OJJAARA oral tablets, momelotinib oral route. GlaxoSmithKline (per FDA), Durham, NC, 2023

Product Information: VONJO oral capsules, pacritinib oral capsules. CTI BioPharma Corp (per FDA), Seattle, WA, 2022.