Dr Sekeres on the Rationale for the FDA Approval of Momelotinib in Myelofibrosis

Mikkael A. Sekeres, MD, MS, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Health System, Sylvester Comprehensive Cancer Center, discusses the background on the FDA approval of momelotinib (Ojjaara) for the treatment of patients with anemic myelofibrosis.

At a recent OncLive® State of the Science Summit™ on hematologic malignancies, Sekeres and colleagues provided updates in the realm of myelodysplastic syndromes. Notably, one of these updates includes the FDA approval of momelotinib for the treatment of adult patients with intermediate or high-risk myelofibrosis with anemia. Originally, the phase 3 SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) trials investigated momelotinib compared with ruxolitinib (Jakafi) and momelotinib compared with best available therapy, respectively, Sekeres begins. In SIMPLIFY-2, although patients receiving momelotinib didn't show a significant improvement in spleen response, they experienced a notable enhancement in symptom score, a benefit that is crucial for patients with myelofibrosis, he reports.

Subsequently, the phase 3 MOMENTUM trial (NCT04173494) was initiated, randomly assigning symptomatic patients with myelofibrosis in a 2:1 ratio to receive either momelotinib or danazol. Notably, significant improvement in symptom scores was observed with momelotinib, Sekeres states, saying that furthermore, substantial improvement in spleen size reduction was noted, forming the basis for momelotinib's FDA approval. Additionally, there was a trend toward enhanced red blood cell transfusion independence rates among patients, Sekeres adds.

Recent updates from the 2023 ASH Annual Meeting unveiled results from phase 3 trials exploring combination therapies, he expands. The phase 3 MANIFEST-2 trial (NCT04603495) evaluating pelabresib (CPI-0610) plus ruxolitinib vs placebo plus ruxolitinib in patients with myelofibrosis, showcased significant spleen shrinkage and a borderline significant enhancement in symptom scores, Sekeres states. Meanwhile, the phase 3 TRANSFORM-1 trial (NCT04472598) investigating navitoclax plus ruxolitinib vs ruxolitinib alone in patients with myelofibrosis demonstrated significant spleen size reduction with the combination, though no significant improvement in total symptom scores was observed.

Overall, these findings indicate an evolving myelofibrosis treatment paradigm, ushering in the era of combination therapy with promising prospects yet to be fully realized, Sekeres concludes.