KEY TAKEAWAYS
- Momelotinib is a JAK1 and JAK2 inhibitor inhibiting ACVR1, with demonstrated benefits in myelofibrosis
- This integrated phase 3 (SIMPLIFY-2) study assessed the long-term safety and survival of momelotinib in myelofibrosis patients.
- The study included 725 myelofibrosis patients who received momelotinib, and 12% remained on therapy for over five years.
- Momelotinib’s investigation revealed a consistent safety profile without cumulative or long-term harm
Momelotinib, a novel JAK1/JAK2 and ACVR1 inhibitor, has demonstrated clinical benefits in treating myelofibrosis by improving anemia, constitutional symptoms, and splenomegaly. This study is one of the largest to date and pooled data from three phase-3 randomized trials of momelotinib (MOMENTUM, SIMPLIFY-1, SIMPLIFY-2) representing myelofibrosis disease from early to late stages. After the 24-week randomized phase, participants in the control arms of the studies—danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY-2—were permitted to transition to momelotinib. Moreover, an extended access protocol enabled all patients to continue receiving momelotinib after completing the studies.
In the pooled analysis of three phase-3 randomized trials, 725 patients with myelofibrosis received momelotinib, with 12% remaining on treatment for five years or more. The median treatment exposure was 11.3 months, ranging from 0.1 to 90.4 months. The most common nonhematologic treatment-emergent adverse event was diarrhea, with an incidence of 27% for any grade and grade ≥3, 3%. Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients. Thrombocytopenia was identified as the most common reason for discontinuation of momelotinib, with a discontinuation rate of 4%. Furthermore, there was no observed increase in the incidence of adverse events of clinical importance, such as infections, malignant transformation, peripheral neuropathy, and bleeding, over time.
The analysis of one of the largest randomized trial databases for a JAK inhibitor in myelofibrosis showed that momelotinib had a consistent safety profile without evidence of long-term or cumulative toxicity.
Source: https://pubmed.ncbi.nlm.nih.gov/37042865/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02101268
Verstovsek S, Mesa RA, Gupta V, Lavie D, Dubruille V, Cambier N, Platzbecker U, Hus M, Xicoy B, Oh ST, Kiladjian JJ, Vannucchi AM, Gerds AT, Egyed M, Mayer J, Sacha T, Kawashima J, Morris M, Huang M, Harrison CN. Momelotinib Long-Term Safety and Survival in Myelofibrosis: Integrated Analysis of Phase 3 Randomized-Controlled Trials. Blood Adv. 2023 Apr 12:bloodadvances.2022009311. doi: 10.1182/bloodadvances.2022009311. Epub ahead of print. PMID: 37042865.
