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HORSHAM, Pa., April 6, 2023 – The Janssen Pharmaceutical Corporations of Johnson & Johnson, in collaboration with its alliance associate, Pharmacyclics, an AbbVie Firm, introduced as we speak the intent to voluntarily withdraw the U.S. indications for IMBRUVICA® (ibrutinib) for the remedy of sufferers with mantle cell lymphoma (MCL) who’ve obtained no less than one prior remedy, and for the remedy of sufferers with marginal zone lymphoma (MZL) who require systemic remedy and have obtained no less than one prior anti-CD20-based remedy. This choice was made in session with the U.S. Meals and Drug Administration (FDA), according to FDA procedural steering on accelerated approvals. This choice doesn’t have an effect on some other accepted indications for IMBRUVICA® within the U.S. Janssen might be speaking straight with healthcare professionals to assist assist sufferers at present receiving remedy with IMBRUVICA® within the U.S. for MCL or MZL.
The FDA beforehand granted approval for IMBRUVICA® in MCL and MZL primarily based on general response charges in two Part 2 scientific research beneath the accelerated approval pathway. Continued approval was contingent upon demonstration of scientific profit within the confirmatory Part 3 SHINE examine (NCT01776840) in beforehand untreated sufferers with MCL, and the confirmatory Part 3 SELENE examine (NCT01974440) in sufferers with relapsed or refractory (R/R) follicular lymphoma (FL) or MZL. The businesses totally enrolled the Part 3 research inside roughly one yr of the accelerated approvals. After discussing the examine outcomes with the businesses, the FDA suggested that the first outcomes from the Part 3 confirmatory research for the indications had been thought of inadequate to assist conversion to full approval.
“We totally assist the FDA accelerated approval pathway, which sufferers depend on for well timed entry to promising remedies that will enhance or prolong their lives. Whereas withdrawing these indications was a troublesome choice, we stay assured within the profit/threat profile of IMBRUVICA in its accepted indications and are dedicated to its continued growth,” mentioned Craig Tendler, M.D., Vice President, Late Improvement and World Medical Affairs, Janssen Analysis & Improvement, LLC. “IMBRUVICA has reworked how sufferers with B-cell malignancies are handled and is probably the most comprehensively studied and prescribed remedy in its class.”
The Part 3 SHINE examine met its main endpoint and demonstrated a major progression-free survival benefit in sufferers with beforehand untreated MCL however didn’t present an general survival benefit. The addition of IMBRUVICA® to chemoimmunotherapy was related to elevated adversarial reactions in comparison with the placebo-controlled arm. The SHINE examine outcomes had been presented throughout the 2022 American Society of Scientific Oncology annual assembly and had been printed in The New England Journal of Medicine. The Part 3 SELENE examine didn’t meet its main endpoint of progression-free survival in sufferers with R/R FL or MZL. The SELENE examine outcomes might be introduced at a future scientific discussion board.
About IMBRUVICA® in MCL and MZL Outdoors the US
IMBRUVICA® has been used to deal with greater than 270,000 sufferers worldwide. This Bruton’s tyrosine kinase (BTK) inhibitor is accepted for R/R MCL in additional than 100 international locations exterior the U.S. primarily based on constructive scientific knowledge from the Part 2 PCYC-1104 examine (NCT01236391) and the randomized Part 3 RAY examine (NCT01646021). As well as, IMBRUVICA® is accepted for R/R MZL in additional than 30 international locations exterior the U.S. primarily based on the Part 2 PCYC-1121 examine (NCT01980628). IMBRUVICA® stays an vital remedy for sufferers and healthcare professionals around the globe.
About MCL and MZL
MCL and MZL, each subtypes of non-Hodgkin’s Lymphoma (NHL), are uncommon and critical blood cancers.1,2 MCL accounts for roughly 5 p.c and MZL accounts for roughly seven p.c of all circumstances of NHL in adults and roughly 80,000 folks might be recognized with NHL in 2023.1,2,3 MCL happens within the white blood cells and is marked by small- to medium-size most cancers cells within the lymph nodes, spleen, bone marrow, blood, or gastrointestinal system.4 MZL happens in white blood cells (lymphocytes) on the edges of lymph nodes and numerous tissues, together with the abdomen, salivary glands, thyroid gland, eyes, lungs and spleen.5,6 MCL and MZL are troublesome to deal with, and subsequently remedy choices are restricted.7,8
About IMBRUVICA®
IMBRUVICA® (ibrutinib) is a once-daily oral remedy that’s collectively developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie firm. IMBRUVICA® blocks the BTK protein, which is required by regular and irregular B cells, together with particular most cancers cells, to multiply and unfold. By blocking BTK, IMBRUVICA® might assist transfer irregular B cells out of their nourishing environments and inhibits their proliferation.9,10,11
IMBRUVICA® is accepted in additional than 100 international locations and has been used to deal with greater than 270,000 sufferers worldwide. There are greater than 50 company-sponsored scientific trials, together with 18 Part 3 research, and greater than 11 years evaluating the efficacy and security of IMBRUVICA®.
IMBRUVICA® was first accepted by the U.S. FDA in November 2013, and as we speak is indicated for grownup sufferers in 4 illness areas, together with three hematologic cancers. These embody indications to deal with adults with continual lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) with or with out 17p deletion (del17p); adults with Waldenström’s macroglobulinemia (WM); and grownup and pediatric sufferers aged one yr and older with beforehand handled continual graft-versus-host illness (cGVHD) after failure of a number of traces of systemic remedy.12
For extra info, go to www.IMBRUVICA.com.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS Hemorrhage: Deadly bleeding occasions have occurred in sufferers who obtained IMBRUVICA®. Main hemorrhage (≥ Grade 3, critical, or any central nervous system occasions; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and put up procedural hemorrhage) occurred in 4.2% of sufferers, with fatalities occurring in 0.4% of two,838 sufferers who obtained IMBRUVICA® in 27 scientific trials. Bleeding occasions of any grade together with bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of sufferers who obtained IMBRUVICA®, respectively.
The mechanism for the bleeding occasions just isn’t effectively understood.
Use of both anticoagulant or antiplatelet brokers concomitantly with IMBRUVICA® will increase the chance of main hemorrhage. Throughout scientific trials, 3.1% of two,838 sufferers who obtained IMBRUVICA® with out antiplatelet or anticoagulant remedy skilled main hemorrhage. The addition of antiplatelet remedy with or with out anticoagulant remedy elevated this proportion to 4.4%, and the addition of anticoagulant remedy with or with out antiplatelet remedy elevated this proportion to six.1%. Think about the dangers and advantages of anticoagulant or antiplatelet remedy when co-administered with IMBRUVICA®. Monitor for indicators and signs of bleeding.
Think about the benefit-risk of withholding IMBRUVICA® for no less than 3 to 7 days pre- and post-surgery relying upon the kind of surgical procedure and the chance of bleeding.
Infections: Deadly and non-fatal infections (together with bacterial, viral, or fungal) have occurred with IMBRUVICA® remedy. Grade 3 or larger infections occurred in 21% of 1,476 sufferers who obtained IMBRUVICA® in scientific trials. Instances of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in sufferers handled with IMBRUVICA®. Think about prophylaxis based on commonplace of care in sufferers who’re at elevated threat for opportunistic infections. Monitor and consider sufferers for fever and infections and deal with appropriately.
Cardiac Arrhythmias, Cardiac Failure, and Sudden Demise: Deadly and critical cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA®. Deaths resulting from cardiac causes or sudden deaths occurred in 1% of 4,896 sufferers who obtained IMBRUVICA® in scientific trials, together with in sufferers who obtained IMBRUVICA® in unapproved monotherapy or mixture regimens. These adversarial reactions occurred in sufferers with and with out preexisting hypertension or cardiac comorbidities. Sufferers with cardiac comorbidities could also be at larger threat of those occasions.
Grade 3 or larger ventricular tachyarrhythmias had been reported in 0.2%, Grade 3 or larger atrial fibrillation and atrial flutter had been reported in 3.7%, and Grade 3 or larger cardiac failure was reported in 1.3% of 4,896 sufferers who obtained IMBRUVICA® in scientific trials, together with in sufferers who obtained IMBRUVICA® in unapproved monotherapy or mixture regimens. These occasions have occurred notably in sufferers with cardiac threat elements together with hypertension and diabetes mellitus, a earlier historical past of cardiac arrhythmias, and in sufferers with acute infections.
Consider cardiac historical past and performance at baseline, and monitor sufferers for cardiac arrhythmias and cardiac operate. Get hold of additional analysis (e.g., ECG, echocardiogram) as indicated for sufferers who develop signs of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest ache), new onset dyspnea, or different cardiovascular issues. Handle cardiac arrhythmias and cardiac failure appropriately, observe dose modification pointers, and take into account the dangers and advantages of continued IMBRUVICA® remedy.
Hypertension: Hypertension occurred in 19% of 1,476 sufferers who obtained IMBRUVICA® in scientific trials. Grade 3 or larger hypertension occurred in 8% of sufferers. Based mostly on knowledge from 1,124 of those sufferers, the median time to onset was 5.9 months (vary, 0.03 to 24 months). Monitor blood strain in sufferers handled with IMBRUVICA®, provoke or modify anti-hypertensive remedy all through remedy with IMBRUVICA® as acceptable, and observe dosage modification pointers for Grade 3 or larger hypertension.
Cytopenias: In 645 sufferers with B-cell malignancies who obtained IMBRUVICA® as a single agent, Grade 3 or 4 neutropenia occurred in 23% of sufferers, Grade 3 or 4 thrombocytopenia in 8% and Grade 3 or 4 anemia in 2.8%, primarily based on laboratory measurements. Monitor full blood counts month-to-month.
Second Main Malignancies: Different malignancies (10%), together with non-skin carcinomas (3.9%), occurred among the many 1,476 sufferers who obtained IMBRUVICA® in scientific trials. Probably the most frequent second main malignancy was non-melanoma pores and skin most cancers (6%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been occasionally reported with IMBRUVICA®. Assess the baseline threat (e.g., excessive tumor burden) and take acceptable precautions. Monitor sufferers intently and deal with as acceptable.
Embryo-Fetal Toxicity: Based mostly on findings in animals, IMBRUVICA® may cause fetal hurt when administered to a pregnant lady. Advise pregnant girls of the potential threat to a fetus. Advise females of reproductive potential to make use of efficient contraception throughout remedy with IMBRUVICA® and for 1 month after the final dose. Advise males with feminine companions of reproductive potential to make use of efficient contraception throughout the identical time interval.
ADVERSE REACTIONS
B-cell malignancies: The most typical adversarial reactions (≥30%) in grownup sufferers with B-cell malignancies (MCL, CLL/SLL, WM and MZL) had been thrombocytopenia (54.5%)*, diarrhea (43.8%), fatigue (39.1%), musculoskeletal ache (38.8%), neutropenia (38.6%)*, rash (35.8%), anemia (35.0%)*, and bruising (32.0%).
The most typical Grade ≥3 adversarial reactions (≥5%) in grownup sufferers with B-cell malignancies (MCL, CLL/SLL, WM and MZL) had been neutropenia (20.7%)*, thrombocytopenia (13.6%)*, pneumonia (8.2%), and hypertension (8.0%).
Roughly 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of grownup sufferers had a dose discount resulting from adversarial reactions. Roughly 4-10% (CLL/SLL), 9% (MCL), and seven% (WM [5%] and MZL [13%]) of sufferers discontinued resulting from adversarial reactions.
cGVHD: The most typical adversarial reactions (≥20%) in grownup or pediatric sufferers with cGVHD had been fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal ache (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), stomach ache (23%), pneumonia (23%), and headache (21%).
The most typical Grade 3 or larger adversarial reactions (≥5%) reported in grownup or pediatric sufferers with cGVHD had been pneumonia (14%), anemia (13%)*, fatigue (12%), pyrexia (11%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), osteonecrosis (9%), stomatitis (9%), hypokalemia (7%), headache (5%), and musculoskeletal ache (5%).
Discontinuation of IMBRUVICA® remedy resulting from an adversarial response occurred in 24% of grownup sufferers and 23% of pediatric sufferers. Opposed reactions resulting in dose discount occurred in 26% of grownup sufferers and 19% of pediatric sufferers.
*Remedy-emergent decreases (all grades) had been primarily based on laboratory measurements.
DRUG INTERACTIONS
CYP3A Inhibitors: Co-administration of IMBRUVICA® with sturdy or reasonable CYP3A inhibitors might enhance ibrutinib plasma concentrations. Elevated ibrutinib concentrations might enhance the chance of drug-related toxicity. Dose modifications of IMBRUVICA® are really useful when used concomitantly with osaconazole, voriconazole, and reasonable CYP3A inhibitors. Keep away from concomitant use of different sturdy CYP3A inhibitors. Interrupt IMBRUVICA® if sturdy inhibitors are used short-term (e.g., for ≤7 days). Keep away from grapefruit and Seville oranges throughout IMBRUVICA® remedy, as these include sturdy or reasonable inhibitors of CYP3A. See dose modification pointers in USPI sections 2.3 and seven.1.
CYP3A Inducers: Keep away from coadministration with sturdy CYP3A inducers.
SPECIFIC POPULATIONS
Pediatric Use:
The protection and effectiveness of IMBRUVICA® have been established for remedy of cGVHD after failure of a number of traces of systemic remedy in pediatric sufferers 1 yr of age and older. The protection and effectiveness of IMBRUVICA® haven’t been established for this indication in pediatric sufferers lower than 1 yr of age.
The protection and effectiveness of IMBRUVICA® in pediatric sufferers haven’t been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, or MZL.
The protection and effectiveness of IMBRUVICA® together with chemoimmunotherapy had been assessed however haven’t been established primarily based on an open-label, randomized examine
(NCT02703272) in 35 sufferers, which included 26 pediatric sufferers age 5 to lower than 17 years, with beforehand handled mature B-cell non-Hodgkin lymphoma. Within the randomized inhabitants, main hemorrhage and discontinuation of chemoimmunotherapy resulting from adversarial reactions occurred extra steadily within the ibrutinib plus chemoimmunotherapy arm in comparison with the chemoimmunotherapy alone arm.
Hepatic Impairment:
Grownup Sufferers with B-cell Malignancies: Hepatic Impairment (primarily based on Baby-Pugh standards): Keep away from use of IMBRUVICA® in sufferers with extreme hepatic impairment. In sufferers with gentle or reasonable impairment, scale back really useful IMBRUVICA® dose and monitor extra steadily for adversarial reactions of IMBRUVICA®.
Sufferers with cGVHD: Keep away from use of IMBRUVICA® in sufferers with whole bilirubin stage > 3x higher restrict of regular (ULN) (until of non-hepatic origin or resulting from Gilbert’s syndrome). Cut back really useful dose when administering IMBRUVICA® to sufferers with whole bilirubin stage >1.5 to 3x ULN (until of non-hepatic origin or resulting from Gilbert’s syndrome).
Please click on here to see the total Prescribing Info
Concerning the Janssen Pharmaceutical Corporations of Johnson & Johnson
At Janssen, we’re making a future the place illness is a factor of the previous. We’re the Pharmaceutical Corporations of Johnson & Johnson, working tirelessly to make that future a actuality for sufferers in every single place by combating illness with science, bettering entry with ingenuity and therapeutic hopelessness with coronary heart. We deal with areas of drugs the place we will make the most important distinction: Cardiovascular, Metabolism & Retina; Immunology; Infectious Ailments & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Be taught extra at www.janssen.com. Observe us at @JanssenUS and @JanssenGlobal. Janssen Biotech, Inc. and Janssen Analysis & Improvement, LLC are a part of the Janssen Pharmaceutical Corporations of Johnson & Johnson.
Cautions Regarding Ahead-Trying Statements
This press launch accommodates “forward-looking statements” as outlined within the Non-public Securities Litigation Reform Act of 1995 relating to IMBRUVICA® (ibrutinib). The reader is cautioned to not depend on these forward-looking statements. These statements are primarily based on present expectations of future occasions. If underlying assumptions show inaccurate or recognized or unknown dangers or uncertainties materialize, precise outcomes may differ materially from the expectations and projections of Janssen Biotech, Inc., Janssen Analysis & Improvement, LLC, any of the opposite Janssen Pharmaceutical Corporations, and/or Johnson & Johnson. Dangers and uncertainties embody, however are usually not restricted to: challenges and uncertainties inherent in product analysis and growth, together with the uncertainty of scientific success and of acquiring regulatory approvals; uncertainty of economic success; manufacturing difficulties and delays; competitors, together with technological advances, new merchandise and patents attained by rivals; challenges to patents; product efficacy or security issues leading to product recollects or regulatory motion; adjustments in habits and spending patterns of purchasers of well being care services and products; adjustments to relevant legal guidelines and laws, together with international well being care reforms; and tendencies towards well being care value containment. An additional listing and descriptions of those dangers, uncertainties and different elements will be present in Johnson & Johnson’s Annual Report on Type 10-Okay for the fiscal yr ended January 1, 2023, together with within the sections captioned “Cautionary Word Relating to Ahead-Trying Statements” and “Merchandise 1A. Danger Components,” and in Johnson & Johnson’s subsequent Quarterly Studies on Type 10-Q and different filings with the Securities and Alternate Fee. Copies of those filings can be found on-line at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Not one of the Janssen Pharmaceutical Corporations nor Johnson & Johnson undertakes to replace any forward-looking assertion because of new info or future occasions or developments.
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[1] Cerhan, J. R., & Habermann, T. M. (2021). Epidemiology of Marginal Zone Lymphoma. Annals of lymphoma, 5, 1. https://doi.org/10.21037/aol-20-28. Final Accessed April 2023.
[2] Lynch DT, Koya S, Acharya U, et al. (2022). Mantle Cell Lymphoma. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK536985. Final Accessed April 2023.
[3] American Most cancers Society. “Key Statistics for Non-Hodgkin Lymphoma.” https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html. Final Accessed April 2023.
[4] Nationwide Most cancers Institute. “Mantle Cell Lymphoma.” https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mantle-cell-lymphoma. Final Accessed April 2023.
[5] Nationwide Most cancers Institute. “MZL.” https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mzl. Final Accessed April 2023.
[6] Lymphoma Analysis Basis. “Marginal Zone Lymphoma.” http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6554677. Final Accessed April 2023.
[7] American Most cancers Society. ‘Varieties of B-cell Lymphoma.” https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/b-cell-lymphoma.html. Final Accessed April 2023.
[8] Cheah CY, Zucca E, Rossi D, Habermann TM. Marginal zone lymphoma: current standing and future views. Haematologica 2022;107(1):35-43; https://doi.org/10.3324/haematol. 2021.278755.
[9] Genetics Residence Reference. Remoted progress hormone deficiency. http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
[10] Turetsky A, et al. Single cell imaging of Bruton’s tyrosine kinase utilizing an irreversible inhibitor. Scientific Studies. 2014;6:4782.
[11] de Rooij MF, et al. The clinically energetic BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in continual lymphocytic leukemia. Blood. 2012;119(11):2590-2594.
[12] IMBRUVICA® U.S. Prescribing Info, August 2022.
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