Ojjaara (momelotinib) Gets FDA Approval for Myelofibrosis

The U.S. Food and Drug Administration (FDA) initially granted Fast Track designation to Ojjaara (momelotinib), a JAK1, JAK2 and ACVR1 inhibitor for the treatment of patients with intermediate/high-risk myelofibrosis who have previously received a JAK inhibitor and subsequent full approval in October 2023.^1,2

“With Ojjaara we have the potential to establish a new standard of care for myelofibrosis patients with anemia,” Ruben A. Mesa, MD, FACP, president and executive director at Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, stated in a press release.

Roughly half of the people with primary myelofibrosis will test positive for a mutation in the Janus kinase 2 (JAK2) gene and the majority of individuals will have overactive JAK signaling even if the don’t have a JAK mutation. This abnormality can be measured by your doctor but doesn’t have to be present for a diagnosis. Increased production of JAK proteins causes the wrong number of blood cells and cytokines to be produced. An enlarged spleen may be detected on physical examination. Bone marrow examination typically reveals an increase in abnormal megakaryocytes (platelet-forming cells) and other abnormalities that are characteristic of myelofibrosis. Jakafi is currently the only FDA approved JAK inhibitor for the treatment of myelofibrosis.

About Ojjaara (momelotinib)

Ojjaara is a selective and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor. More than 1200 individuals have received Ojjaara since clinical studies began in 2009, including more than 800 treated for myelofibrosis. Ojjaara is believed to have a differentiated therapeutic profile encompassing many of the constitutional symptom improvements, a range of meaningful anemia benefits, including eliminating or reducing the need for frequent blood transfusions, and comparable spleen control to Jakafi (ruxolitinib).

A previous study of momelotinib failed to meet the study goal of reducing spleen volume, but data from that study suggested that momelotinib therapy might provide meaningful results for patients previously treated with Jakafi, including improved anemia responses, fewer transfusion requirements, and symptom improvement. The MOMENTUM study was designed to measure that benefit.²

About MOMENTUM 

MOMENTUM is a Phase 3 study designed to evaluate the activity of Ojjaara versus Danazol in symptomatic, anemic patients with several myeloproliferative neoplasms including Primary Myelofibrosis, Post-Polycythemia Vera (PV) Myelofibrosis, or Post Essential Thrombocythemia (ET) Myelofibrosis. 

The clinical trial was launched in Q4 2019 and was designed to enroll 180 patients who were symptomatic and anemic and had been treated previously with a JAK inhibitor. Patients were treated with either Ojjaara or danazol and directly compared. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive Ojjaara.^3,4

Preliminary study results were released at ASCO and ASH 2022; in symptomatic and anemic patient, Ojjaara was found to be superior to danazol for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival according to the study authors.

Final data leading to FDA approval showed that 25% of patients treated with Ojjaara experienced a 50% or greater improvement compared with 9% of those treated with danazol.  Thirty percent of patient who were given Ojjaara achieved transfusion independence compared to 20% of those who received danazol.

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References:

1. Sierra Announces Momelotinib Granted FDA Fast Track Designation
2. Harrison CN, Vannucchi AM, Platzbecker U, et al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 December 20.
3. Mesa RA, Gerds AT, Vannucchi A, et al. MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. Abstract presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract 7002.
4. Gerds AT, Mesa RA, Vannucchi AM, et al. Updated results from the Momentum phase 3 study of momelotinib (MMB) versus danazol (DAN) in sympatomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. Presented at: 2022 ASH Annual Meeting; December 10-13, 2022; New Orleans, LA. Abstract 627

5. Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed September 15, 2023. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia

6. Verstovsek S, Gerds AT, Vannuchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0