Momelotinib Receives FDA Approval for Myelofibrosis With Anemia

"I think [momelotinib] will make an immediate impact. There clearly are individuals now who are on JAK inhibitors like ruxolitinib [Jakafi] or fedratinib [Inbrec] who have significant anemia who will immediately be potential candidates," according to Ruben A. Mesa, MD.

The News

The FDA has approved momelotinib (Ojjaara) for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary and secondary myelofibrosis, who are experiencing anemia, according to a press release from GSK.¹ 

The approval was based on results from the phase 3 MOMENTUM trial (NCT04173494), which was previously presented at the 2022 American Society of Clinical Oncology Annual Meeting, with other supporting data coming from a subpopulation of the phase 3 SIMPLIFY-1 trial (NCT01969838). ^2,3

Momelotinib, a once daily oral JAK1/2 inhibitor, is the only approved treatment for this indication.

Expert Perspective

“I think [momelotinib] will make an immediate impact. There clearly are individuals now who are on JAK inhibitors like ruxolitinib [Jakafi] or fedratinib [Inbrec] who have significant anemia who will immediately be potential candidates,” Ruben A. Mesa, MD, said in an interview with CancerNetwork^® prior to the approval. “We’ll see how the [National Comprehensive Cancer Network] guidelines form but there’s a case to be made for consideration [for momelotinib] as the initial JAK inhibitor selected for people who have significant anemia.”

Mesa is the president of the Enterprise Cancer Service Line and senior vice president at Atrium Health; executive director of the National Cancer Institute-designated Atrium Health Wake Forest Baptist Comprehensive Cancer Center; and vice dean for Cancer Programs at Wake Forest University School of Medicine

The MOMENTUM Trial

The MOMENTUM trial included 195 patients who were randomly assigned 2:1 to receive either momelotinib (n = 130) at 200 mg per day plus placebo or danazol (n = 65) at 600 mg per day plus placebo. At week 24 patients in the danazol arm were allowed to crossover to the momelotinib arm. The primary end point was total symptom score at week 24, and the secondary end points included transfusion independence and splenic response rate.

In the momelotinib arm, 27.7% of patients discontinued treatment for several reasons including adverse effects (AEs; n = 16), patient decision (n = 6), or death (n = 4). In the danazol arm, 41.5% of patients discontinued treatments because of AEs (n = 11), patient decision (n = 5), or death (n = 3). Additionally, 4 patients crossed over to the momelotinib arm early.

The median age in the momelotinib arm was 71.0 years vs 72.0 years in the danazol arm, 60.8% vs 67.7% were male, and 82.3% vs 76.9% were White, respectively. In terms of myelofibrosis subtype, 60.0% of those in the momelotinib arm had a primary subtype vs 70.8% in the danazol arm, 20.8% vs 16.9% had post-polycythemia vera, and 19.2% vs 12.3% had post-essential thrombocytopenia.

At week 24, the total symptom score response rate was 24.6% (95% CI, 17.49%-32.94%)in the momelotinib arm vs 9.2% (95% CI, 3.46%-19.02%) in the danazol arm (P = .0095). Moreover, 40.0% (95% CI, 31.51%-48.95%) of patients in the momelotinib arm had a 25% reduction in splenic volume vs 6.2% (95% CI, 1.70%-15.01%; P <.0001) in the danazol arm. Additionally, 35% reduction in spleen volume was observed in 23.1% (95% CI, 16.14%-31.28%) in the momelotinib arm and 3.1% (95% CI, 0.37%-10.68%; P = .0006) in the danazol arm.

At baseline, the transfusion independence rate at baseline was 13% in the momelotinib arm vs 15% in the danazol arm. Comparatively, the rate week 24 was 31% in the momelotinib arm vs 20% in the danazol arm (P = .0064).

SIMPLIFY-1 Trial

In this randomized, multicenter study, momelotinib was investigated vs ruxolitinib (Rituxan) in patients who had not received prior treatment with a JAK inhibitor. A total of 432 patients were analyzed with patients received 200 mg orally daily of momelotinib or 20 mg of ruxolitinib once per day.

A 50% of more reduction in the total symptom score was observed in 28.4% of patients receiving momelotinib vs 42.2% receiving ruxolitinib (P = .98). Momelotinib improved the transfusion rate, transfusion independence, and transfusion dependence (P ≤ .19).

Safety

In terms of safety findings from the MOMENTUM trial, the most common grade 3 or higher nonhematologic AEs included acute kidney injury (3.1% vs 9.2%), nausea (2.3% vs 3.1%), and dyspnea (2.3% vs 1.5%) in the momelotinib and danazol arms, respectively. Hematologic AEs of grade 3 or higher included anemia (60.8% vs 75.4%), thrombocytopenia (27.7% vs 26.2%), and neutropenia (12.3% vs 9.2%) in the momelotinib and danazol arms, respectively.

Grade 3 or higher AEs occurred in 53.8% vs 64.6%, and serious AEs occurred in 34.6% vs 40.0% of patients in the momelotinib and danazol arms, respectively. Investigators reported a hazard ratio (HR) of 0.734 (95% CI, 0.382-1.409; P = .3510) for overall survival overall and 0.506 up to week 24 (95% CI, 0.238-1.076; P = .0719).

Safety data from the SIMLIFY-1 trial indicated that AEs occurred in 7% of patients who received momelotinib vs 3% who received ruxolitinib. In 10% of patients, treatment-related neuropathy occurred with momelotinib treatment vs 5% with ruxolitinib.

References

1. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia, News release. GSK. September 15, 2023. September 15, 2023.
2. Mesa RA, Gerds AT, Vannucchi A, et al. MPN-478 MOMENTUM: phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. J Clin Oncol. 2022;40(suppl 16):7002. doi:10.1200/JCO.2022.40.16_suppl.7002
3. Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis. J Clin Oncol. 2017;34(suppl 34):3844-3850. doi:10.1200/JCO.2017.73.4418