Glaxosmithkline Regulatory News (GSK)

Issued: 2 December 2022, London UK

European Medicines Agency accepts marketing authorisation application for momelotinib for the treatment of myelofibrosis

· Application includes data from key phase III trials, including the pivotal MOMENTUM trial, which met all primary and key secondary efficacy endpoints

GSK plc (LSE/NYSE: GSK) today announced that the European Medicines Agency (EMA) validated the marketing authorisation application (MAA) for momelotinib, a potential new oral treatment for myelofibrosis. Momelotinib has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, and JAK2 and activin A receptor type I (ACVR1), which could address the significant medical needs of myelofibrosis patients with anaemia.

The MAA is based on results from key phase III trials, including the pivotal MOMENTUM trial, which met all primary and key secondary endpoints, including Total Symptom Score (TSS), Transfusion Independence (TI) rate and Splenic Response Rate (SRR). The primary analysis data from the MOMENTUM phase III trial were presented at the 2022 American Society of Clinical Oncology Annual Meeting and the European Hematology Association 2022 Hybrid Congress. Updated 48-week data will be presented at the upcoming American Society of Hematology (ASH) Annual Meeting and Exposition on 10-13 December 2022.

A Committee for Medicinal Products for Human Use (CHMP) regulatory action is anticipated by year-end 2023, and a New Drug Application for momelotinib is currently under regulatory review with the US Food and Drug Administration (FDA) with a Prescription Drug User Fee Act action date of 16 June 2023. Momelotinib is not currently approved in any market, but if approved by regulators, momelotinib would be the only medicine that addresses key manifestations of myelofibrosis, including anaemia, symptoms, and splenomegaly.

About the pivotal MOMENTUM phase III clinical trial

MOMENTUM is a global, randomised, double-blind phase III clinical trial of momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anaemic and had been previously treated with a US FDA-approved JAK inhibitor. The trial was designed to evaluate the safety and efficacy of momelotinib for treating and reducing key hallmarks of the disease: symptoms, blood transfusions (due to anaemia) and splenomegaly (enlarged spleen).

The trial's primary efficacy endpoint was TSS reduction of ≥50% over the 28 days immediately before the end of Week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form. Key secondary endpoints included TI rate for ≥12 weeks immediately before the end of Week 24 with haemoglobin levels ≥ 8 g/dL and SRR based on splenic volume reduction of ≥35% at Week 24 from baseline.

Patients were randomised at 2:1 to receive either momelotinib or danazol (n=130 and n=65, respectively). After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early crossover to momelotinib was available for confirmed splenic progression. The trial enrolled 195 patients across 21 countries.

About momelotinib

Momelotinib is a potential new medicine with a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1 and JAK2 and activin A receptor type I (ACVR1).[i],[ii],[iii],[iv] Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.i,ii,iv Additionally, direct inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is elevated in myelofibrosis and contributes to anaemia.i,ii,iii,iv

About myelofibrosis

Myelofibrosis is a rare blood cancer that results from dysregulated JAK-signal transducer and activator of transcription protein signalling and is characterised by constitutional symptoms, splenomegaly, and progressive anaemia. Myelofibrosis affects approximately 20,000 patients in the US, with about 40% of patients already anaemic at the time of diagnosis and nearly all patients estimated to develop anaemia eventually.i,[v] Patients will often require transfusions, and more than 30% will discontinue treatment due to anaemia.[vi] Anaemia and transfusion dependence strongly correlate with poor prognosis and shortened survival.[vii]

GSK in oncology

GSK is focused on maximising patient survival through transformational medicines. GSK's pipeline is focused on immuno-oncology, tumour cell targeting therapies and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, and antibody-drug conjugates, either alone or in combination.

About GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com/company.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK's Q3 Results for 2022 and any impacts of the COVID-19 pandemic.

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[i] Chifotides, H.T., Bose, P. & Verstovsek, S. Momelotinib: an emerging treatment for myelofibrosis patients with anemiaanaemia. J Hematol Oncol 15, 7 (2022). https://doi.org/10.1186/s13045-021-01157-4

[ii] Verstovsek S, et al. MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic. Future Oncol. 2021;17(12):1449-1458. https://doi.org/10.2217/fon-2020-1048

[iii] Asshoff M, et al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood. 2017;129(13):1823-1830.

[iv] Oh S, et al. ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. Blood Adv. 2020;4(18):4282-4291.

[v] Naymagon, L., & Mascarenhas, J. (2017). Myelofibrosis-Related Anemia: Current and Emerging Therapeutic Strategies. HemaSphere, 1(1), e1. https://doi.org/10.1097/HS9.0000000000000001

[vi] Palandri, F., Palumbo, G.A., Elli, E.M. et al. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis. Blood Cancer J. 11, 4 (2021). https://doi.org/10.1038/s41408-020-00392-1

[vii] Pardanani, A., & Tefferi, A. (2011). Prognostic relevance of anemia and transfusion dependency in myelodysplastic syndromes and primary myelofibrosis. Haematologica, 96(1), 8-10. https://doi.org/10.3324/haematol.2010.035519