REG - GSK PLC - GSK receives positive CHMP opinion for momelotinib

GSKAnnouncement

13/11/2023 07:00

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RNS Number : 1607T  GSK PLC  13 November 2023

Issued: 13 November 2023, London UK

 

GSK receives positive CHMP opinion recommending momelotinib for myelofibrosis
patients with anaemia

 

·      If approved, momelotinib will become the first and only treatment
in the EU specifically indicated for myelofibrosis patients with moderate to
severe anaemia

·      Decision on EU marketing authorisation expected for momelotinib
by early 2024

 

GSK plc (LSE/NYSE: GSK) today announced the Committee for Medicinal Products
for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a
positive opinion recommending approval of momelotinib for the treatment of
disease-related splenomegaly (enlarged spleen) or symptoms in adult patients
with moderate to severe anaemia who have primary myelofibrosis, post
polycythaemia vera myelofibrosis or post essential thrombocythaemia
myelofibrosis and who are Janus kinase (JAK) inhibitor naïve or have been
treated with ruxolitinib.

 

The CHMP opinion is one of the final steps prior to a marketing authorisation
decision by the European Commission. If approved, momelotinib would be the
only medicine in the European Union (EU) specifically indicated for both newly
diagnosed and previously treated myelofibrosis patients with moderate to
severe anaemia that addresses splenomegaly and symptoms.

 

Nina Mojas, Senior Vice President, Oncology Global Product Strategy, GSK,
said: "Momelotinib has a differentiated mechanism of action that may address
the significant medical needs of myelofibrosis patients, especially those with
moderate to severe anaemia. The vast majority of myelofibrosis patients will
develop anaemia, causing them to require transfusions and leading a notable
proportion to discontinue treatment. This positive CHMP opinion is a
significant step in bringing momelotinib to patients in the EU with this
difficult-to-treat blood cancer."

 

The positive CHMP opinion is supported by data from the pivotal MOMENTUM study
and a subpopulation of adult patients with moderate to severe anaemia
(haemoglobin <10 g/dL) from the SIMPLIFY-1 phase III trial. 1 (,)2 MOMENTUM
was designed to evaluate the safety and efficacy of momelotinib versus danazol
for the treatment and reduction of key manifestations of myelofibrosis in an
anaemic, symptomatic, JAK inhibitor-experienced population. SIMPLIFY-1 was
designed to evaluate the efficacy and safety of momelotinib versus ruxolitinib
in myelofibrosis patients who had not received a prior JAK-inhibitor therapy.

 

In these clinical trials, the most common adverse reactions were diarrhoea,
thrombocytopaenia, nausea, headache, dizziness, fatigue, asthenia, abdominal
pain and cough.(1, 2 )

 

If approved in the EU, momelotinib will be available under the proposed trade
name Omjjara. This opinion follows the September 2023 approval
(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/)
of momelotinib under the brand name Ojjaara by the US Food and Drug
Administration (FDA) for the treatment of intermediate or high-risk
myelofibrosis, including primary myelofibrosis or secondary myelofibrosis
(post-polycythaemia vera and post-essential thrombocythaemia), in adults with
anaemia. Momelotinib is not approved in any other 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).(1, 3 , 4 , 5 ) Inhibition of JAK1 and JAK2 may
improve constitutional symptoms and splenomegaly.1(,)3(,)5 Additionally,
inhibition of ACVR1 leads to a decrease in circulating hepcidin levels,
potentially contributing to anaemia benefit.1(,)3(,)4(,)5

 

About myelofibrosis

Myelofibrosis is a rare blood cancer that disrupts the body's normal
production of blood cells because of dysregulated JAK-signal transducer and
activator of transcription protein signalling. The clinical hallmarks of
myelofibrosis are splenomegaly (enlarged spleen), progressive anaemia and
debilitating constitutional symptoms, such as fatigue, night sweats and bone
pain, attributable to ineffective haematopoiesis and excessive production of
proinflammatory cytokines. 6 

 

About 40% of patients 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. 7 (, 8 , 9 , 10 ) Myelofibrosis patients with anaemia require
additional supportive care, including transfusions, and more than 30% will
discontinue treatment due to anaemia. 11  Patients who are transfusion
dependent have a poor prognosis and shortened
survival.3(, 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 )

 

About the pivotal clinical trials

MOMENTUM was a phase III, global, multicentre, randomised, double-blind study
investigating momelotinib versus danazol in patients with myelofibrosis who
were symptomatic and anaemic and had been previously treated with an 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. The MOMENTUM trial met
all its primary and key secondary endpoints, demonstrating statistically
significant response with respect to constitutional symptoms, splenic response
and transfusion independence, in patients treated with momelotinib versus
danazol.(( 20 )) Results from the 24-week randomised 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), 21 (, 22 )
with 48-week data presented at the 64th American Society of Hematology (ASH)
Annual Meeting and Exposition in December 2022 and subsequently published in
The Lancet
(https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(23)00174-6/fulltext). 23 (, 24 )

 

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.
Safety and efficacy results for SIMPLIFY-1 were based upon a subset of
patients with anaemia at baseline. The efficacy of momelotinib in the
treatment of patients with myelofibrosis in SIMPLIFY-1 was based on spleen
volume response (reduction of spleen volume by 35% or greater).

 

GSK in oncology

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

 

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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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 under
Item 3.D 'Risk factors" in the company's Annual Report on Form 20-F for 2022,
and Q3 Results for 2023.

 

 

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 1  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.

 2  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;35(34):3844-3850.

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

 4  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.

 5  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.

 6  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.

 7  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

 8  Bose P, et al. Curr Hematol Malign Rep. 2018;13:164-172. doi:
https://doi.org/10.3109/10428194.2013.813500

 9  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

 10  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

 11  Kuykendall AT, Shah S, Talati C, et al. Between a rux and a hard place:
evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib
discontinuation. Ann Hematol. 2018;97(3):435-441.

 12  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

 13  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

 14  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

 15  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

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

 17  QxMD. DIPSS plus score for prognosis of myelofibrosis. Accessed September
12, 2022.

 18  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

 19  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

 20  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.

 21  Mesa R, et al. Presented at: American Society of Clinical Oncology; June
2022. Abstract 7002.

 22  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  Gerds AT, et al. Presented at: American Society of Hematology; December
2022. Abstract 627.

 24  Gerds AT, et al. Momelotinib versus danazol in symptomatic patients with
anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM):
an updated analysis of an international, double-blind, randomised phase 3
study. The Lancet Haematology. 2023;10(9):E735-E746.
https://doi.org/10.1016/S2352-3026(23)00174-6

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