Clinical trial evidence for fedratinib came from JAKARTA 2, a single-arm, open-label, phase 2 study. The study included 97 adults with intermediate or high-risk primary myelofibrosis, post-polycythaemia vera myelofibrosis, or post-essential thrombocythaemia myelofibrosis that was deemed resistant to ruxolitinib after at least 14 days of treatment, or who were intolerant to ruxolitinib after any duration of treatment. Of these people, 81 had intermediate 2 or high-risk disease, corresponding to where the company positioned fedratinib. Clinical trial evidence for people who have stopped ruxolitinib suggests that fedratinib improves myelofibrosis symptoms and reduces spleen size. However, this evidence is uncertain because fedratinib was not compared with best available therapy and some people did not finish the trial. The committee acknowledged the difficulty of collecting data for rare diseases. It concluded that fedratinib is clinically effective, but that the disruption to the trial and lack of comparative data made the assessment of comparative effectiveness challenging. Fedratinib has been compared indirectly with best available therapy using evidence from other studies. However, there is further uncertainty because of some differences between the trial populations in the indirect comparison. Also, it is unclear how much longer people having fedratinib live compared with best available therapy, and this has a large effect on the cost-effectiveness results. There is also uncertainty around how many people would continue having fedratinib if their disease does not fully respond, or stops responding. The committee considered the deterministic incremental cost-effectiveness ratios (ICERs) for fedratinib compared with best available therapy. Because of a confidential commercial arrangement for ruxolitinib, the exact cost-effectiveness results cannot be reported here. The analyses accounting for a survival benefit for fedratinib resulted in ICERs less than £30,000 per quality-adjusted life year (QALY) gained, but the analyses without a survival benefit resulted in ICERs greater than this. The committee considered that the most plausible ICER was likely to be between the scenarios with and without a survival benefit for fedratinib applied. However, this ICER would likely be above £30,000 per QALY gained, the upper end of the range normally considered a cost-effective use of NHS resources when the end of life criteria are not met. The committee concluded that fedratinib could not be recommended for routine use in the NHS. Collecting more data on overall survival and treatment duration will reduce the uncertainty in the evidence. Therefore, fedratinib is recommended for use in the Cancer Drugs Fund. The committee concluded that fedratinib met the criteria for inclusion in the Cancer Drugs Fund for treating disease-related splenomegaly or symptoms of primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis in adults who have previously had ruxolitinib.