Myelofibrosis is a rare haematological malignancy characterised by splenomegaly and debilitating symptoms, which has limited therapeutic options and significant unmet clinical need. Current first-line therapy options for myelofibrosis are two Janus kinase (JAK) inhibitors (JAKis), namely Incyte’s Jakavi/Jakafi (ruxolitinib) and Impact Biomedicine’s Inrebic (fedratinib). On 28 February, the US Food and Drug Administration (FDA) approved the third JAKi to reach the myelofibrosis market, CTI BioPharma’s Vonjo (pacritinib), for the treatment of intermediate/high-risk myelofibrosis patients with platelets below 50×109/L who are ineligible for other JAKis. Vonjo is, therefore, uniquely positioned to treat this critically underserved patient population, which previously had no approved treatment options.

The FDA granted Accelerated Approval to pacritinib based on results from the pivotal Phase III PERSIST-2 trial, in which Vonjo demonstrated clinical efficacy for myelofibrosis patients with thrombocytopaenia. Patients were randomised at a 1:1:1 ratio to receive Vonjo 200mg twice daily, Vonjo 400mg once daily, or best available therapy (BAT) (including Jakafi). Patients with low platelets (< 50 x109/L) showed a durable splenic response, with 29% of this cohort showing spleen volume reduction of more than 35%, compared with 3% on BAT.

According to key opinion leaders (KOLs) interviewed by GlobalData, there is scope for Vonjo to target myelofibrosis patients with moderate thrombocytopenia (platelets between 50×109/L and 100×109/L), as Jakafi shows moderate efficacy in this patient population, and the PERSIST-2 trial demonstrated superior splenic volume reduction and total symptom reduction in this patient population compared with BAT. Jakafi is, however, well-established as a first-line treatment for myelofibrosis and benefits from a first-to-market advantage, as it was the first FDA-approved therapy for myelofibrosis. This first-to-market advantage granted it clinician familiarity and confidence, which may provide resistance to prescribing Vonjo for this patient population. The use of Vonjo in this patient population is, therefore, contingent upon demonstrating superiority to ruxolitinib.

“Pacritinib, potentially, [is] useful in people with platelets between 50-100[x109/L]. But can you answer the question, is it superior to ruxolitinib? A tough one. You can’t say for sure.” US Key Opinion Leader

GlobalData’s analyst consensus forecast estimates annual sales of Vonjo to reach $235m by 2027. Several other pipeline agents are in pivotal Phase III trials, but Vonjo’s market share is secured by targeting a patient population distinct from those of other pipeline agents. The myelofibrosis treatment paradigm is set to experience significant developments over the next five years, with several additional FDA approvals imminently anticipated, such as Sierra Oncology’s momelotinib, which is expected to be approved later this year.  

MoleculeCompanyMechanism of action
OB-756Huadong PharmaceuticalJAKi
JaktinibSuzhou Zelgen BiopharmaceuticalJAKi
FedratinibImpact BiosciencesJAKi
MomelotinibSierra OncologyJAKi
PelabresibMorphoSys/Constellation PharmaceuticalsBETi
Navtemadlin (KRT-232)Kartos TherapeuticsMDM2i