REG - GSK PLC - Momelotinib filing accepted in Japan

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11/09/2023 07:00

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RNS Number : 9376L  GSK PLC  11 September 2023

Issued: 11 September 2023, London UK

 

GSK regulatory submission for momelotinib for the treatment of myelofibrosis
accepted for review by Japanese regulator

 

·   Regulatory submission included data from pivotal trials addressing key
clinical manifestations of myelofibrosis, namely splenomegaly, constitutional
symptoms and anaemia

 

 

GSK plc (LSE/NYSE: GSK) today announced that the Ministry of Health, Labour
and Welfare (MHLW), Japan, has accepted for review a new drug application
(NDA) for momelotinib, a potential new medicine with a differentiated
mechanism of action that may address the significant medical needs of
myelofibrosis patients, especially those with anaemia. The NDA is based on
data from the pivotal phase III trials SIMPLIFY-1 and MOMENTUM.

 

Myelofibrosis is a blood cancer that can lead to splenomegaly (enlarged
spleen); constitutional symptoms such as fatigue, night sweats, and bone pain;
and severely low blood counts, including anaemia and thrombocytopenia. 1 
(#_edn1) (, 2  (#_edn2) , 3  (#_edn3) ) About 70% of patients diagnosed with
primary myelofibrosis and about half of patients diagnosed with secondary
myelofibrosis in Japan have moderate to severe anaemia at the time of
diagnosis, and nearly all patients are estimated to develop anaemia over the
course of the disease. 4  (#_edn4) (, 5  (#_edn5) , 6  (#_edn6) , 7  (#_edn7)
, 8  (#_edn8) , 9  (#_edn9) ) Patients who are transfusion dependent have a
poor prognosis and shortened survival. 10  (#_edn10) (, 11  (#_edn11) , 12 
(#_edn12) , 13  (#_edn13) , 14  (#_edn14) , 15  (#_edn15) , 16  (#_edn16)
, 17  (#_edn17) , 18  (#_edn18) )

 

Momelotinib is not currently approved in any market.

 

About momelotinib

Momelotinib has a differentiated mechanism of action, with inhibitory ability
along three key signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A
receptor, type I (ACVR1). 19  (#_edn19) (, 20  (#_edn20) , 21  (#_edn21) , 22 
(#_edn22) ) Inhibition of JAK1 and JAK2 may improve constitutional symptoms
and splenomegaly.(19)(,)(21)(,)(22) Additionally, inhibition of ACVR1 leads to
a decrease in circulating hepcidin, which is elevated in myelofibrosis and
contributes to anaemia.(19)(,)(20)(,)(21)(,)(22)

 

About myelofibrosis

Myelofibrosis is a rare blood cancer that disrupts the body's normal
production of blood cells as a result of dysregulated JAK-signal transducer
and activator of transcription protein signalling. The clinical hallmarks of
myelofibrosis are progressive splenomegaly (enlarged spleen), anaemia and
debilitating symptoms attributable to ineffective hematopoiesis and excessive
production of proinflammatory cytokines. 23  (#_edn23) Myelofibrosis patients
with anaemia require additional supportive care, including transfusions, and
have poor outcomes. 24  (#_edn24) (, 25  (#_edn25) ) Myelofibrosis affects
approximately 1 in 500,000 people worldwide, with up to 5,000 patients
impacted in Japan.(10)(,)(19)(, 26  (#_edn26) , 27  (#_edn27) )

 

About the pivotal SIMPLIFY-1 clinical trial

SIMPLIFY-1 was a multicentre randomised, double-blind, phase III study that
compared the safety and efficacy of momelotinib to ruxolitinib in patients
with myelofibrosis who had not received prior treatment with a JAK inhibitor.
SIMPLIFY-1 met its primary endpoint, demonstrating non-inferiority of
momelotinib to ruxolitinib in spleen volume response (reduction by 35% or
greater), and substantial improvements in transfusion independence rates. 28 
(#_edn28) (, 29  (#_edn29) )

 

About the pivotal MOMENTUM clinical trial

MOMENTUM was a global, randomised, double-blind phase III clinical trial of
momelotinib (MMB) versus danazol (DAN) in patients with myelofibrosis who were
symptomatic and anaemic and had been previously treated with an approved JAK
inhibitor. The MOMENTUM trial met all its primary and key secondary endpoints,
with respect to splenic response, constitutional symptoms and transfusion
independence. Results from the 24-week treatment period were presented at the
2022 American Society of Clinical Oncology (ASCO) Annual Meeting and
subsequently published in The Lancet
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02036-0/fulltext).(22)(, 30 
(#_edn30) )

( )

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GSK is committed to maximising patient survival through transformational
medicines, with a current focus on breakthroughs in immuno-oncology and
tumor-cell targeting therapies, and development in haematologic malignancies,
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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.

 

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 1  (#_ednref1) NIH National Library of Medicine. Primary Myelofibrosis.
September 2014. Accessed 5 August 2022.
https://medlineplus.gov/genetics/condition/primary-myelofibrosis/

 2  (#_ednref2) MPN Research Foundation. Primary Myelofibrosis (PMF). 2021.
Accessed August, 2022.
http://www.mpnresearchfoundation.org/primary-myelofibrosis-pmf/

 3  (#_ednref3) National Organization for Rare Disorders (NORD). Primary
Myelofibrosis. 2018. Accessed 9 August 2022.
https://rarediseases.org/rare-diseases/primary-myelofibrosis/

 4  (#_ednref4) Takenaka K et al., Clinical features and outcomes of patients
with primary myelofibrosis in Japan: report of a 17-year nationwide survey by
the Idiopathic Disorders of Hematopoietic Organs Research Committee of Japan.
Int J Hematol. 2017 Jan;105(1):59-69. doi: 10.1007/s12185-016-2102-3

 5  (#_ednref5) Tefferi A, Lasho TL, Jimma T, et al. One thousand patients
with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc.
2012;87(1):25-33. doi:10.1016/j.mayocp.2011.11.001

 6  (#_ednref6) Bose P, et al. Curr Hematol Malign Rep. 2018;13:164-172. doi:
https://doi.org/10.3109/10428194.2013.813500

 7  (#_ednref7) Scherber, R.M., Mesa, R. Management of challenging
myelofibrosis after JAK inhibitor failure and/or progression. Blood Rev.
2020;42:100716. https://doi.org/10.1016/j.blre.2020.100716

 8  (#_ednref8) Bassiony S, Harrison CN, McLornan DP. Evaluating the Safety,
Efficacy, and Therapeutic Potential of Momelotinib in the Treatment of
Intermediate/High-Risk Myelofibrosis: Evidence to Date. Ther Clin Risk Manag.
2020;16:889-901. Published 2020 Sep 25. doi:10.2147/TCRM.S258704

 9  (#_ednref9) Shide K et al. Nationwide prospective survey of secondary
myelofibrosis in Japan: superiority of DIPSS-plus to MYSEC-PM as a survival
risk model. Blood Cancer J. 2023;13(1):110. doi: 10.1038/s41408-023-00869-9

 10  (#_ednref10) Naymagon, L., Mascarenhas, J. Myelofibrosis-Related Anemia:
Current and Emerging Therapeutic Strategies. HemaSphere. 2017;1(1):e1. doi:
10.1097/HS9.0000000000000001

 11  (#_ednref11) How J, Hobbs GS. A Practical Guide for Using Myelofibrosis
Prognostic Models in the Clinic. J Natl Compr Canc Netw. 2020;18(9):1271-1278.
https://doi.org/10.6004/jnccn.2020.7557

 12  (#_ednref12) Nicolosi M, et al. Sex and degree of severity influence the
prognostic impact of anemia in primary myelofibrosis: analysis based on 1109
consecutive patients. Leukemia. 2018;32(5):1254-1258.
https://doi.org/10.1038/s41375-018-0028-x

 13  (#_ednref13) Tefferi A, et al. Use of the Functional Assessment of Cancer
Therapy--anemia in persons with myeloproliferative neoplasm-associated
myelofibrosis and anemia. Clin Ther. 2014;36(4):560-566.
https://doi.org/10.1016/j.clinthera.2014.02.016

 14  (#_ednref14) Tefferi A. Primary myelofibrosis: 2021 update on diagnosis,
risk-stratification and management. Am J Hematol. 2021;96(1):145-162.
https://doi.org/10.1002/ajh.26050

 15  (#_ednref15) Rumi E, et al. The Genetic Basis of Primary Myelofibrosis
and Its Clinical Relevance. Int J Mol Sci. 2020;21(23):8885.
https://doi.org/10.3390/ijms21238885

 16  (#_ednref16) QxMD. DIPSS prognosis in myelofibrosis. Accessed September
12, 2022.
https://qxmd.com/calculate/calculator_187/dipss-prognosis-in-myelofibrosis.

 17  (#_ednref17) QxMD. DIPSS plus score for prognosis of myelofibrosis.
Accessed September 12, 2022.

 18  (#_ednref18) Elena C, et al. Red blood cell transfusion-dependency
implies a poor survival in primary myelofibrosis irrespective of IPSS and
DIPSS. Haematologica. 2011;96(1):167-170.
https://doi.org/10.3324/haematol.2010.031831

 19  (#_ednref19) Chifotides, HT, Bose, P, Verstovsek, S. Momelotinib: an
emerging treatment for myelofibrosis patients with anemia. J Hematol Oncol.
2022;15(7):1-18.

 20  (#_ednref20) 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.

 21  (#_ednref21) 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.

 22  (#_ednref22) Verstovsek S, et al. Momelotinib versus danazol in
symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from
an international, double-blind, randomised, controlled, phase 3 study. The
Lancet. 2023;401(10373):269-280.

 23  (#_ednref23) Atallah E, Verstovsek S. Emerging drugs for myelofibrosis.
Expert Opin Emerg Drugs. 2012 Dec;17(4):555-70. doi:
10.1517/14728214.2012.748748. PMID: 23186315; PMCID: PMC5009610.

 24  (#_ednref24) Chifotides, H.T., Bose, P. & Verstovsek, S. Momelotinib:
an emerging treatment for myelofibrosis patients with anemia. J Hematol Oncol
15, 7 (2022). https://doi.org/10.1186/s13045-021-01157-4

 25  (#_ednref25) Naymagon L, Mascarenhas J. Myelofibrosis-Related Anemia:
Current and Emerging Therapeutic Strategies. Hemasphere. 2017 Dec 20;1(1):e1.
doi: 10.1097/HS9.0000000000000001. PMID: 31723730; PMCID: PMC6745971.

 26  (#_ednref26) Data on file. Sierra Oncology. 2021.

 27  (#_ednref27) Myelofibrosis - Epidemiology Forecast - 2032. DelveInsight.
2022;1-60.

 28  (#_ednref28) Mesa R, et al. Presented at: ISPOR 2021.

 29  (#_ednref29) Mesa R, et al. Presented at: SOHO 2021. Poster MPN-303.

 30  (#_ednref30) Mesa R, et al. Presented at: American Society of Clinical
Oncology; June 2022. Abstract 7002.

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