Tag Archives: momelotinib

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

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Mikkael A. Sekeres, MD, MS

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.

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Utilization of Momelotinib for Myelofibrosis With Anemia Can Result in Small Savings

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Laura Joszt, MA

Although momelotinib to treat myelofibrosis (MF) with anemia has a higher acquisition cost, it is partially offset by savings when transfusion-related costs are reduced, according to a poster being presented at the AMCP Annual Conference, held April 15-18, 2024, in New Orleans, Louisiana.1

MF is a rare cancer in the bone marrow that disrupts the production of blood cells.2 MF causes anemia because of the extensive scarring to bone marrow. This extensive scarring also causes patients to have a low number of platelets, increasing their risk of bleeding. Patients may also have an enlarged spleen.

Momelotinib inhibits Janus kinase (JAK) 1, JAK2, and activin A receptor type 1. In September 2023, the FDA approved momelotinib to treat patients with intermediate- or high-risk MF with anemia.3

The approval of momelotinib was based on data from the phase 3 MOMENTUM trial, which found clinically significant improvements for patients treated with momelotinib vs danazol.4 A quarter of patients treated with momelotinib had a 50% or greater reduction in total symptom score compared with only 16% of patients on danazol.

Since the approval, the National Comprehensive Cancer Network (NCCN) has added momelotinib5 to its Clinical Practice Guidelines in Oncology for Myeloproliferative Neoplasms. Momelotinib was added as a category 2A treatment for patients with high-risk MF. It was also added as a 2B category treatment for patients with lower-risk MF.

Patients with MF who have anemia and are dependent on transfusions have increased medical costs and poor prognosis, the authors of the AMCP poster noted. JAK inhibitors may provide improvements in symptoms and spleen size, but they could worsen or induce anemia. However, momelotinib has been shown to reduce spleen size.4

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Momelotinib for myelofibrosis: our 14 years of experience with 100 clinical trial patients and recent FDA approval

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Ayalew Tefferi & Animesh Pardanani

Momelotinib is an ATP-competitive small molecule inhibitor of Janus kinase proteins (JAKi), including JAK1, JAK2, JAK3, and TYK2; its other clinically relevant targets include activin A receptor type 1 (ACVR1), also known as activin receptor like kinase 2 (ALK2) [1]. Momelotinib was recently approved (September 15, 2023) for use in anemic patients with high/intermediate risk myelofibrosis (MF), including primary (PMF) [2] and secondary variants, the latter emerging from antecedent polycythemia vera (post-PV) [3] or essential thrombocythemia (post-ET) [4]. All three MF variants belong to the broader category of myeloproliferative neoplasms (MPNs), which are characterized by the presence of JAK-STAT activating mutations (JAK2, CALR or MPL) and predominantly megakaryocytic myeloproliferation with variable degrees of bone marrow fibrosis [5]. Patients with MF face premature death with 10-year survival estimates ranging from >80% in very low-risk diseases to <5% in very high-risk diseases [6]. In addition, the clinical course of the disease in MF is complicated by progressive anemia, extramedullary hematopoiesis with marked splenomegaly and hepatomegaly, constitutional symptoms, and cachexia. Causes of death in MF include disease transformation into acute myeloid leukemia [7].

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European Commission Approves Momelotinib for Myelofibrosis/Anemia

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Ariana Pelosci

The European Commission granted marketing authorization to momelotinib (Omjjara) for patients with primary myelofibrosis who have disease-related splenomegaly or moderate to severe anemia, according to a press release from GSK.1

This indication also covers patients with post polycythemia vera myelofibrosis or post essential thrombocythemia myelofibrosis who are JAK inhibitor naïve or received previous treatment with ruxolitinib (Jakafi). The authorization is based on results from the phase 3 MOMENTUM trial (NCT04173494), which analyzed the use of momelotinib and danazol in patients with symptomatic and anemic myelofibrosis.2

“The challenges of living with myelofibrosis can be burdensome, and symptomatic patients can experience spleen enlargement, fatigue, night sweats, and bone pain. Until now, there have been no options specifically indicated to treat these symptoms in patients who also experience anemia. The authorization of [momelotinib] brings a new treatment option with a differentiated mechanism of action to these patients in the European Union,” Nina Mojas, senior vice president of Oncology Global Product Strategy at GSK, said in the press release.

In the trial, the total symptom score response at week 24 was 24.6% (95% CI, 17.49%-32.94%) for patients receiving momelotinib vs 9.2% (95% CI, 3.46%-19.02%) in the danazol arm (P = .0095). Additionally, a reduction of splenic volume by 25% occurred in 40.0% (95% CI, 31.51%-48.95%) of patients in the momelotinib arm vs 6.2% (95% CI, 1.70%-15.01%; P <.0001) in the danazol arm. A 35% reduction in spleen volume was also 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.

In September 2023, the FDA approved momelotinib for patients with intermediate- or high-risk myelofibrosis, including primary and secondary myelofibrosis, who are experiencing anemia.3 In November 2023, the European Medicine’s Agency’s Committee for Medicinal Products for Human Use expressed a positive opinion for momelotinib.4 The positive opinion was one of the final steps leading to the approval of the drug in the European Union.

“I think [momelotinib] will make an immediate impact. There clearly are individuals now who are on JAK inhibitors like ruxolitinib or fedratinib [Inrebic] who have significant anemia who will immediately be potential candidates,” Ruben A. Mesa, MD, FACP, said in an interview with CancerNetwork® prior to the FDA approval. 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.

References

  1. European Commission authorises GSK’s Omjjara (momelotinib). News release. GSK. January 29, 2024. Accessed January 29, 2024. https://shorturl.at/ntuvy
  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. Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia, News release. GSK. September 15, 2023. Accessed January 29, 2024. https://shorturl.at/jnNQY
  4. GSK receives positive CHMP opinion recommending momelotinib for myelofibrosis patients with anaemia. News release. GSK. November 13, 2023. Accessed January 29, 2024. https://bit.ly/3MEYpOl

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