- Approval is for use in myelofibrosis patients with anemia
regardless of prior myelofibrosis therapy
- Nearly all myelofibrosis patients are estimated to develop
anemia over the course of the disease, and over 30% will
discontinue treatment due to anemia1,2,3
- Ojjaara addresses key manifestations of myelofibrosis, namely
anemia, constitutional symptoms and splenomegaly
GSK plc (LSE/NYSE: GSK) today announced that the US Food and
Drug Administration (FDA) has approved Ojjaara (momelotinib) for
the treatment of intermediate or high-risk myelofibrosis, including
primary myelofibrosis or secondary myelofibrosis (post-polycythemia
vera and post-essential thrombocythemia), in adults with anemia.
Ojjaara is a once-a-day, oral JAK1/JAK2 and activin A receptor type
1 (ACVR1) inhibitor. To date, it is the only approved medicine for
both newly diagnosed and previously treated myelofibrosis patients
with anemia that addresses the key manifestations of the disease,
namely anemia, constitutional symptoms, and splenomegaly (enlarged
spleen).4
Nina Mojas, Senior Vice President, Oncology Global Product
Strategy, GSK, said: “The vast majority of myelofibrosis
patients eventually develop anemia, causing them to discontinue
treatments and require transfusions. Given this high unmet need, we
are proud to add Ojjaara to our oncology portfolio and address a
significant medical need in the community. We look forward to
helping improve outcomes in this difficult-to-treat blood
cancer.”
Myelofibrosis is a blood cancer affecting approximately 25,000
patients in the US.4,5,6 Myelofibrosis can lead to severely low
blood counts, including anemia and thrombocytopenia; constitutional
symptoms such as fatigue, night sweats, and bone pain; and
splenomegaly. About 40% of patients have moderate to severe anemia
at the time of diagnosis, and nearly all patients are estimated to
develop anemia over the course of the disease.7,8,9,10 Physicians
have had limited treatment options to treat myelofibrosis patients
with anemia. These patients often require transfusions and more
than 30% will discontinue treatment due to anemia.3 Patients who
are transfusion dependent have a poor prognosis and shortened
survival.1,11,12,13,14,15,16,17,18
Ruben A. Mesa, MD, FACP, President and Executive Director,
Atrium Health Levine Cancer Center and Atrium Health Wake Forest
Baptist Comprehensive Cancer Center, said: “With momelotinib we
have the potential to establish a new standard of care for
myelofibrosis patients with anemia. Addressing key manifestations
of myelofibrosis, including anemia, constitutional symptoms and
splenomegaly, makes a significant difference in the treatment
regimen for these patients who have limited options to address
these aspects of the disease.”
The FDA approval of momelotinib is supported by data from the
pivotal MOMENTUM study and a subpopulation of adult patients with
anemia from the SIMPLIFY-1 phase III trial. 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 anemic, symptomatic, JAK inhibitor-experienced
population. 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.2 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.1
Safety and efficacy results for SIMPLIFY-1 were based upon a subset
of patients with anemia.
In these clinical trials, the most common adverse reactions were
thrombocytopenia, hemorrhage, bacterial infection, fatigue,
dizziness, diarrhea, and nausea.19
Kapila Viges, Chief Executive Officer, MPN
(Myeloproliferative Neoplasms) Research Foundation,
said: “We are thrilled to see momelotinib reach the clinic,
giving patients and their physicians another option to help manage
myelofibrosis. Any new treatment that takes steps toward unlocking
the mysteries of this complex and chronic blood cancer represents
great progress for the field.”
Momelotinib is currently not approved in any other market.
About myelofibrosis Myelofibrosis is a rare blood cancer
that results from dysregulated JAK-signal transducer and activator
of transcription protein signaling and is characterized by
constitutional symptoms, splenomegaly, and progressive anemia.
Myelofibrosis affects approximately 25,000 patients in the
US.1,5,6
About the pivotal MOMENTUM clinical trial MOMENTUM was a
phase III, global, multicenter, randomized, double-blind study
investigating momelotinib versus danazol in patients with
myelofibrosis who were symptomatic and anemic 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 anemia) and splenomegaly.2 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.20,21
About the SIMPLIFY-1 clinical trial SIMPLIFY-1 was a
multicenter, randomized, 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 anemia (hemoglobin <10
g/dL) at baseline. The efficacy of momelotinib in the treatment of
patients with myelofibrosis in SIMPLIFY-1 was based on spleen
volume response (reduction by 35% or greater).
About Ojjaara (momelotinib) Ojjaara has a differentiated
mechanism of action, with inhibitory ability along three key
signaling pathways: Janus kinase (JAK) 1, JAK2, and activin A
receptor, type I (ACVR1).2,6,22,23 Inhibition of JAK1 and JAK2 may
improve constitutional symptoms and splenomegaly.2,6,23
Additionally, inhibition of ACVR1 leads to a decrease in
circulating hepcidin, which is elevated in myelofibrosis and
contributes to anemia.2,6,22,23
INDICATION OJJAARA is indicated for the treatment of
intermediate or high-risk myelofibrosis (MF), including primary MF
or secondary MF [post-polycythemia vera (PV) and post-essential
thrombocythemia (ET)], in adults with anemia.
IMPORTANT SAFETY INFORMATION Risk of
Infections
- Serious (including fatal) infections (e.g., bacterial and
viral, including COVID-19) occurred in 13% of patients treated with
OJJAARA. Infections regardless of grade occurred in 38% of
patients. Delay starting therapy until active infections have
resolved. Monitor patients for signs and symptoms of infection and
initiate appropriate treatment promptly.
Hepatitis B Reactivation
- Hepatitis B viral load (HBV-DNA titer) increases, with or
without associated elevations in alanine transaminase (ALT) or
aspartate transaminase (AST), have been reported in patients with
chronic hepatitis B virus (HBV) infection taking Janus Kinase (JAK)
inhibitors, including OJJAARA. The effect of OJJAARA on viral
replication in patients with chronic HBV infection is unknown. In
patients with HBV infections, check hepatitis B serologies prior to
starting OJJAARA. If HBsAg and/or anti-HBc antibody is positive,
consider consultation with a hepatologist regarding monitoring for
reactivation versus prophylactic hepatitis B therapy. Patients with
chronic HBV infection who receive OJJAARA should have their chronic
HBV infection treated and monitored according to clinical HBV
guidelines.
Thrombocytopenia and Neutropenia
- New or worsening thrombocytopenia, with platelet count less
than 50 × 109/L, was observed in 20% of patients treated with
OJJAARA. Eight percent of patients had baseline platelet counts
less than 50 × 109/L.
- Severe neutropenia, absolute neutrophil count (ANC) less than
0.5 × 109/L, was observed in 2% of patients treated with
OJJAARA.
- Assess complete blood counts (CBC), including platelet and
neutrophil counts, before initiating treatment and periodically
during treatment as clinically indicated. Interrupt dosing or
reduce the dose for thrombocytopenia or neutropenia.
Hepatotoxicity
- Two of the 993 patients with MF who received at least one dose
of OJJAARA in clinical trials experienced reversible drug-induced
liver injury. Overall, new or worsening elevations of ALT and AST
(all grades) occurred in 23% and 24%, respectively, of patients
treated with OJJAARA; Grade 3 and 4 transaminase elevations
occurred in 1% and 0.5% of patients, respectively. New or worsening
elevations of total bilirubin occurred in 16% of patients treated
with OJJAARA. All total bilirubin elevations were Grades 1-2. The
median time to onset of any grade transaminase elevation was 2
months, with 75% of cases occurring within 4 months.
- Delay starting therapy in patients presenting with uncontrolled
acute and chronic liver disease until apparent causes have been
investigated and treated as clinically indicated. When initiating
OJJAARA, refer to dosing in patients with hepatic impairment.
- Monitor liver tests at baseline, every month for 6 months
during treatment, then periodically as clinically indicated. If
increases in ALT, AST or bilirubin related to treatment are
suspected, modify OJJAARA dosage based upon Table 1 within the
Prescribing Information.
Major Adverse Cardiovascular Events (MACE)
- Another JAK inhibitor increased the risk of MACE, including
cardiovascular death, myocardial infarction, and stroke [compared
with those treated with tumor necrosis factor (TNF) blockers] in
patients with rheumatoid arthritis, a condition for which OJJAARA
is not indicated.
- Consider the benefits and risks for the individual patient
prior to initiating or continuing therapy with OJJAARA,
particularly in patients who are current or past smokers and
patients with other cardiovascular risk factors. Inform patients
receiving OJJAARA of the symptoms of serious cardiovascular events
and the steps to take if they occur.
Thrombosis
- Another JAK inhibitor increased the risk of thrombosis,
including deep venous thrombosis, pulmonary embolism, and arterial
thrombosis (compared with those treated with TNF blockers) in
patients with rheumatoid arthritis, a condition for which OJJAARA
is not indicated. Evaluate patients with symptoms of thrombosis and
treat appropriately.
Malignancies
- Another JAK inhibitor increased the risk of lymphoma and other
malignancies excluding nonmelanoma skin cancer (NMSC) (compared
with those treated with TNF blockers) in patients with rheumatoid
arthritis, a condition for which OJJAARA is not indicated. Current
or past smokers were at increased risk.
- Consider the benefits and risks for the individual patient
prior to initiating or continuing therapy with OJJAARA,
particularly in patients with a known malignancy (other than a
successfully treated NMSC), patients who develop a malignancy, and
patients who are current or past smokers.
Adverse Reactions
- The most common adverse reactions (≥20% in either study) are
thrombocytopenia, hemorrhage, bacterial infection, fatigue,
dizziness, diarrhea, and nausea.
Organic Anion Transporting Polypeptide (OATP)1B1/B3
Inhibitors
- Momelotinib is an OATP1B1/B3 substrate. Concomitant use with an
OATP1B1/B3 inhibitor increases momelotinib maximal concentrations
(Cmax) and area under the concentration-time curve (AUC), which may
increase the risk of adverse reactions with OJJAARA. Monitor
patients concomitantly receiving an OATP1B1/B3 inhibitor for
adverse reactions and consider OJJAARA dose modifications.
Breast Cancer Resistance Protein (BCRP) Substrates
- Momelotinib is a BCRP inhibitor. OJJAARA may increase exposure
of BCRP substrates, which may increase the risk of BCRP substrate
adverse reactions. When administered concomitantly with OJJAARA,
initiate rosuvastatin (BCRP substrate) at 5 mg and do not increase
to more than 10 mg once daily. Dose adjustment of other BCRP
substrates may also be needed. Follow approved product information
recommendations for other BCRP substrates.
Pregnancy
- Available data in pregnant women are insufficient. OJJAARA
should only be used during pregnancy if the expected benefits to
the mother outweigh the potential risks to the fetus.
Lactation
- It is not known whether OJJAARA is excreted in human milk.
Because of the potential for serious adverse reactions in a
breastfed child, patients should not breastfeed during treatment
with OJJAARA, and for at least 1 week after the last dose of
OJJAARA.
Females and Males of Reproductive Potential
- Advise females of reproductive potential who are not pregnant
to use highly effective contraception during therapy and for at
least 1 week after the last dose of OJJAARA.
Hepatic Impairment
- Momelotinib exposure increased with severe hepatic impairment
(Child-Pugh C). The recommended starting dose of OJJAARA in
patients with severe hepatic impairment (Child-Pugh C) is 150 mg
orally once daily. No dose modification is recommended for patients
with mild hepatic impairment (Child-Pugh A) or moderate hepatic
impairment (Child-Pugh B).
Please see full Prescribing Information,
including Patient Information, for OJJAARA.
GSK in oncology GSK is committed to maximizing patient
survival through transformational medicines, with a current focus
on breakthroughs in immuno-oncology and tumor-cell targeting
therapies, and development in hematologic malignancies, gynecologic
cancers and other solid tumors.
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.
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 Q2 Results for 2023 and any impacts of the COVID-19
pandemic.
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Current and Emerging Therapeutic Strategies. HemaSphere.
2017;1(1):e1. 2 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. 3 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. 4 Harrison C, et al. Presented at:
European Hematology Association; June 2022. Poster EP1113. 5 Data
on file. Sierra Oncology. 2021. 6 Chifotides, HT, Bose, P,
Verstovsek, S. Momelotinib: an emerging treatment for myelofibrosis
patients with anemia. J Hematol Oncol. 2022;15(7):1-18. 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
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
12 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 13 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 14 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 15 QxMD. DIPSS prognosis in
myelofibrosis. Accessed September 12, 2022.
https://qxmd.com/calculate/calculator_187/dipss-prognosis-in-myelofibrosis.
16 QxMD. DIPSS plus score for prognosis of myelofibrosis. Accessed
September 12, 2022. 17 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 18 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 Mesa RA, Kiladjian
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20 Mesa R, et al. Presented at: American Society of Clinical
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Momelotinib versus danazol in symptomatic patients with anaemia and
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double-blind, randomised, controlled, phase 3 study. The Lancet.
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