Vincristine Sulfate

The European MCL Network Phase 3 TRIANGLE study, evaluated ibrutinib in combination with induction immunochemotherapy, both with and without an autologous stem cell transplant, followed by 24 months fixedduration ibrutinib therapy1 Both ibrutinib-based regimens, transplant-free and with transplant, delivered clinically meaningful improvement in efficacy compared to the current standard of care of induction immunochemotherapy followed by transplant2 BEERSE, BELGIUM (18 December 2024) – Janssen-Cilag International NV, a Johnson & Johnson company, today announced the submission of a Type II variation application to the European Medicines Agency (EMA). The submission seeks approval for an indication extension of IMBRUVICA® (ibrutinib) in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL), who are eligible for autologous stem cell transplant (transplant). This regulatory submission is supported by data from the TRIANGLE study, conducted by the European MCL Network. “Mantle cell lymphoma remains an incurable and challenging disease to treat, particularly in younger patients in need of durable frontline options,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “The TRIANGLE study demonstrates ibrutinib's potential to replace or compliment a transplantbased regimen, offering eligible patients a more effective path to long term remission and representing the first major step forward in frontline mantle cell lymphoma treatment in years.” The proposed indication is supported by results from the Phase 3 TRIANGLE study (NCT02858258) which investigated 870 patients across three treatment arms: standard induction immunochemotherapy followed by transplant, induction immunochemotherapy plus ibrutinib followed by transplant and 2-year fixed-duration ibrutinib therapy, and induction immunochemotherapy plus ibrutinib without transplant, followed by 2-year fixed-duration ibrutinib therapy.2,3 Prolonged efficacy and safety data from the TRIANGLE study were recently presented by the principal investigator Prof. Dr. Martin Dreyling, Ludwig Maximilian University of Munich, as an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting.3 “At Johnson & Johnson, we are committed to investing in innovation that transforms clinical outcomes for those living with complex blood cancers, including mantle cell lymphoma,” said Jessica Vermeulen, Vice President, Oncology Late Development, Johnson & Johnson Innovative Medicine. “Today’s submission to the EMA could represent a pivotal step in moving beyond transplant as the frontline standard of care for younger patients with mantle cell lymphoma.” About Ibrutinib Ibrutinib is a once-daily oral medication that is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.4 Ibrutinib blocks the BTK protein, which is needed by normal and abnormal B-cells, including specific cancer cells, to multiply and spread.5 By blocking BTK, ibrutinib may help move abnormal B-cells out of their nourishing environments and inhibits their proliferation. 6 Ibrutinib is approved in more than 100 countries and has been used to treat more than 300,000 patients worldwide.7 There are more than 50 companysponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of ibrutinib.4,8 In October 2021, ibrutinib was added to the World Health Organization’s Model Lists of Essential Medicines (EML), which refers to medicines that address global health priorities and which should be available and affordable for all.9 Ibrutinib was first approved by the European Commission (EC) in 2014, and approved indications to date include:4 As a single agent or in combination with rituximab or obinutuzumab or venetoclax for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) As a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy As a single agent for the treatment of adult patients with relapsed or refractory MCL As a single agent for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. In combination with rituximab for the treatment of adult patients with WM For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics. About Mantle Cell Lymphoma (MCL) MCL is an aggressive type of blood cancer that originates from the B lymphocytes, a functional component of the human immune system.10 The overall incidence of MCL globally is approximately 1-2 cases per 100,000 persons per year and it has a higher prevalence in men than women.11 MCL typically affects individuals at 65-years of age at diagnosis.11 While patient outcomes have dramatically improved over the latest few decades, MCL remains a difficult disease to treat with many patients relapsing or becoming resistant to therapy.11 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at www.innovativemedicine.jnj.com/emea. Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Biologics B.V. and Janssen Research & Development, LLC are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements  This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of ibrutinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC, Janssen Biologics B.V. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at https://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC, Janssen Biologics B.V. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 ClinicalTrials.gov. ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma. NCT02858258. Available at: https://clinicaltrials.gov/study/NCT02858258. Last accessed: December 2024. 2Dreyling et al., Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. The Lancet, 2024; 403:10441:2293 - 2306 3Dreyling at al., Role of Autologous Stem Cell Transplantation in the Context of Ibrutinib-Containing First-Line Treatment in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial By the European MCL Network. Oral presentation. Abstract # 240. 2024 American Society of Hematology Annual Meeting. 4European Medicines Agency. IMBRUVICA Summary of Product Characteristics. September 2023. Available at: https://www.ema.europa.eu/en/documents/product-information/imbruvica-epar-product-information_en.pdf. Last accessed: December 2024. 5Turetsky A, et al. Single cell imaging of Bruton's tyrosine kinase using an irreversible inhibitor. Sci Rep. 2014;4:4782 6de Rooij MF, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012. 119(11):2590-2594 7 J&J Data on File (RF-419273). Global number of cumulative patients treated with Ibrutinib since launch. June 2024. 8 Pollyea DA, et al. A Phase I Dose Escalation Study of the Btk Inhibitor PCI-32765 in Relapsed and Refractory B Cell Non-Hodgkin Lymphoma and Use of a Novel Fluorescent Probe Pharmacodynamic Assay. Blood. 2009. 114(22): 3713 9World Health Organization. WHO prioritizes access to diabetes and cancer treatments in new Essential Medicines Lists. Available at: https://www.who.int/news/item/01-10-2021-who-prioritizes-access-to-diabetes-and-cancer-treatments-in-new-essential-medicines-lists. Last accessed: December 2024. 10Jain P. and Wang M. L., Mantle cell lymphoma in 2022-A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments, American Journal of Hematology. 2022; 97;5:638–56. 11Dreyling, M. et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 2017; 28:62-71 Media contact: Jenni Mildon JMildon@its.jnj.com +44 7920 418 552 Investor contact: Lauren Johnson   investor-relations@its.jnj.com

Exploratory long-term follow-up analysis of the phase III POLARIX study indicated a positive trend in overall survival in favour of Polivy in combination with R-CHP for people with first-line diffuse large B-cell lymphoma (DLBCL)1 Patients treated with Polivy in combination with R-CHP required fewer subsequent treatments, potentially reducing burdens on patients and healthcare systems1 These encouraging five-year results continue to highlight the potential of this Polivy combination to improve outcomes in first-line DLBCL, an area that previously had little advancement in nearly two decades 8 December 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today data from a five-year follow-up of the pivotal phase III POLARIX study evaluating Polivy® (polatuzumab vedotin) in combination with MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with untreated diffuse large B-cell lymphoma (DLBCL). Data were presented in an oral session at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, 7-10 December 2024 in San Diego, US. This latest analysis conducted after a median follow-up of 60.9 months, includes descriptive data on primary and secondary endpoints, as well as safety results.1 “POLARIX was the first trial to elevate treatment standards for frontline diffuse large B-cell lymphoma in 20 years and we are additionally encouraged by the five-year follow-up results,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “More than 38,000 people worldwide have been treated with Polivy in combination with R-CHP and these data continue to underscore its potential to improve outcomes for people diagnosed with this aggressive lymphoma.” Follow-up exploratory analysis after five-years indicated a positive trend in overall survival (OS) in the intent-to-treat (ITT) population in favour of Polivy in combination with R-CHP compared to MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Results showed a trend in reduction in the risk of death (HR 0.85; 95% CI: 0.63–1.15) for people with previously untreated DLBCL with the Polivy combination, an improvement on the three-year follow-up data (HR 0.94; 95% CI: 0.67–1.33). The five-year analysis of POLARIX indicates that the full difference in OS between treatment arms has yet to be observed and an additional two years of follow-up will continue.1 “Diffuse large B-cell lymphoma is a notoriously challenging cancer to treat, however, Polivy in combination with R-CHP has shown to be a critical advance for patients by helping to reduce relapse and disease progression,” said Gilles Salles, MD, PhD, Chief of Lymphoma Service, Division of Hematological Malignancies, Memorial Sloan Kettering Cancer Center, US. “The survival trend seen in this follow-up analysis reinforces the potential impact of frontline treatment with Polivy in combination with R-CHP and its role as a standard of care therapy.” In addition to the positive trend in OS, an observational analysis suggested nearly 25% fewer follow-up treatments such as radiation, systemic chemotherapy and CAR-T cell therapy were needed in patients receiving Polivy in combination with R-CHP compared to those treated with R-CHOP (38.3% vs 61.7%).1 Based on findings from a previous economic analysis which found that total healthcare costs increased with each additional line of treatment in relapsed or refractory DLBCL, a reduction in the number of subsequent therapies could potentially alleviate some of the burdens associated with relapse and disease progression.2 At five years of follow-up, benefits in progression-free survival and disease-free survival with Polivy in combination with R-CHP were maintained, consistent with the three-year follow-up data, reinforcing the potential of Polivy in combination with R-CHP to provide durable and lasting remissions. The latest follow-up data also showed a numerical reduction in death related to patients’ lymphoma in those treated with Polivy in combination with R-CHP compared to those treated with R-CHOP (9.0% vs 11.4%). The safety profile remains consistent with the known profiles of the individual study medicines with no new safety signals observed, reinforcing the positive benefit-risk profile of this Polivy combination.1 Results from an expanded cohort of 1,000 patients including global and Chinese patients demonstrated comparability to the global ITT population.1 Polivy in combination with R-CHP is currently approved for the treatment of first-line (1L) DLBCL in more than 90 countries worldwide including the US, countries throughout the EU, the UK, Japan, Canada and China. Roche continues to work with health authorities around the world to bring this treatment regimen to even more patients. Roche aims to offer various treatment options for DLBCL that meet the diverse needs of patients and healthcare systems. In an effort to elevate treatment standards even further, Roche is exploring Polivy in combination with other molecules including its bispecific antibodies. Studies include the phase III SUNMO trial evaluating the efficacy and safety of subcutaneously administered Lunsumio® (mosunetuzumab) in combination with intravenous (IV) Polivy versus IV MabThera/Rituxan plus gemcitabine and oxaliplatin (R-GemOx) in second-line or later DLBCL, and the phase III SKYGLO trial investigating the efficacy of Polivy in combination with R-CHP and Columvi® (glofitamab) versus Polivy in combination with R-CHP in 1L DLBCL. POLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy® (polatuzumab vedotin) plus MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by MabThera/Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera/Rituxan. The primary outcome measure is progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goal of first-line therapy: decreasing the risk of disease worsening. Overall survival is a secondary endpoint in the POLARIX study. DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.3 DLBCL is an aggressive (fast-growing) type of NHL. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. 4,5 Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes. Approximately 160,000 people worldwide are estimated to be diagnosed with DLBCL each year.1,6 Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells. Polivy is being developed by Roche using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL. Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan, Gazyva®/Gazyvaro® (obinutuzumab), Polivy, Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3 and Tecentriq® (atezolizumab). Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Gilles S, et al. Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes. Presented at: ASH Annual Meeting and Exposition; 2024 Dec 7-10; San Diego, CA, USA. Abstract #469. [2] Gatwood J, et al. Total cost of care in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Presented at: ASH Annual Meeting and Exposition; 2022, Dec 10-13. Abstract #3527 [3] Cancer.Net. Lymphoma - Non-Hodgkin: Subtypes. [Internet; cited December 2024]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes [4] Sehn LH, et al. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-858. [5] Maurer MJ, et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32:1066-73. [6] World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet [Internet; cited December 2024]. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pd. The content above comes from the network. if any infringement, please contact us to modify.