Fallopian Tube High Grade Serous Adenocarcinoma

BEERSE, Belgium, 21 April 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the European Commission (EC) has granted marketing authorisation for AKEEGA® (niraparib and abiraterone acetate [AA]), in the form of a dual action tablet (DAT), given with prednisone or prednisolone, for the treatment of adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic) in whom chemotherapy is not clinically indicated.2Prostate cancer is the most common cancer in men in Europe, and the sixth-highest cause of cancer-related death worldwide.1,2 Despite treatment advances, mCRPC remains an incurable, deadly disease.3,4 BRCA1/2 gene mutations have been identified in approximately 10-15 percent of mCRPC patients5,6 and are more likely to cause aggressive disease, poor outcomes, and a shorter survival time.7,8,9,10“Metastatic castration-resistant prostate cancer remains a lethal disease, with high unmet needs in terms of treatment options, particularly for patients with BRCA1/2 gene mutations,” said Professor Gerhardt Attard, Oncologist, University College London (UCL), London, UK*. “We’ve seen that in these patients, niraparib combined with abiraterone acetate and predniso(lo)ne (AAP) significantly reduced the risk of disease progression or death compared to AAP. The dual action tablet of niraparib with abiraterone acetate is a promising first line targeted treatment option for men with mCRPC and BRCA1/2 mutations.”The EC authorisation, which also marks the first worldwide approval for AKEEGA®, is based on results of the randomised, double-blind, placebo controlled, Phase 3 MAGNITUDE study (NCT03748641).11 The trial assessed whether the addition of niraparib to AAP improved outcomes in those with untreated mCRPC, with or without alterations in homologous recombination repair (HRR) associated genes (which are involved in the repair of damaged DNA), including BRCA1/2.1,14 A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations, making it the largest cohort of BRCA1/2-positive patients with first line mCRPC in any clinical study to date.12“The MAGNITUDE trial was prospectively designed as a precision medicine study to identify the specific population of patients who would most benefit from niraparib with abiraterone acetate plus predniso(lo)ne, and potentially increase the likelihood of treatment success,” said Martin Vogel, EMEA Therapeutic Area Lead Oncology, Janssen-Cilag GmbH. “The results, on which this European Commission approval is based, reinforce the benefit of this niraparib-based combination in effectively addressing BRCA mutations and changing the outlook for patients with mCRPC.”The primary endpoint for MAGNITUDE was radiographic progression-free survival (rPFS), as analysed by blinded central review.1,14 Niraparib plus AAP significantly improved rPFS in all HRR-positive patients (Hazard Ratio [HR] 0.73; 95 percent Confidence Interval [CI], 0.56 to 0.96; p=0.022).3 This improvement was most pronounced in patients with BRCA1/2 gene mutations, where a statistically significant 47 percent risk reduction was observed for rPFS.3 With additional median follow-up at 24.8 months in the BRCA subgroup, rPFS by central review demonstrated a consistent and clinically meaningful treatment effect favouring niraparib plus AAP, with a median rPFS of 19.5 months compared with 10.9 months for placebo plus AAP.1 Additionally, there was a trend towards improved overall survival (OS) with niraparib plus AAP, strong improvement in time to symptomatic progression (TSP) and clinically meaningful improvement in time-to-initiation of cytotoxic chemotherapy (TCC).1The observed safety profile of the combination of niraparib and AAP was consistent with the known safety profile of each agent.3 Of the patients with HRR gene alterations, 67 percent experienced Grade 3/4 adverse events (AEs) in the combination arm versus 46.4 percent in the control arm.13 The most common grade 3 AEs were anaemia (28.3 percent versus 7.6 percent) and hypertension (14.6 percent versus 12.3 percent) with niraparib and AAP versus placebo and AAP, respectively.16 The combination of niraparib and AAP also maintained overall quality of life in comparison with placebo and AAP.3,16“This European milestone, which also marks the first worldwide approval for AKEEGA®, highlights the value of precision medicine and the importance of genetic testing in patients with mCRPC to ensure the right patients receive the right treatment,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “It also demonstrates our ongoing commitment at Janssen to developing innovative therapeutic approaches to help improve outcomes for patients living with prostate cancer.”Niraparib is a highly selective poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.14 Together with AA plus prednisone, the combination DAT regimen targets two oncogenic drivers in patients with mCRPC, namely alterations in the androgen receptor axis and in BRCA1/2.14,17,18 This is the first DAT formulation available in the European Union for patients with mCRPC with BRCA mutations.2Europe is the first region to approve AKEEGA® (niraparib and abiraterone acetate DAT), for the treatment of patients with BRCA-positive mCRPC, globally. In February 2023, Janssen submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval of this niraparib-based combination for the treatment of patients with BRCA-positive mCRPC.16#ENDS#About NiraparibNiraparib is an orally administered, highly selective poly (ADP ribose) polymerase (PARP) inhibitor, that is currently being studied by Janssen for the treatment of patients with prostate cancer.2,20 Additional ongoing studies include the Phase 3 AMPLITUDE study (NCT04497844) evaluating the combination of niraparib and AAP in a homologous recombination repair (HRR) biomarker-selected patient population with metastatic hormone-sensitive prostate cancer (mHSPC).17In April 2016, Janssen Biotech, Inc. entered into a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GSK in 2019),18 for exclusive rights to niraparib in prostate cancer.19In the European Economic Area (EEA), niraparib is already indicated as monotherapy for the maintenance treatment of adult patients with advanced epithelial high-grade ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response following completion of first-line platinum-based chemotherapy; and as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.17 In these indications, niraparib is currently marketed by GSK as ZEJULA®.17AKEEGA® is a dual action tablet (DAT) combining niraparib and abiraterone acetate (AA). It is available in two dose strengths: regular-strength (100 mg niraparib/500 mg AA) and low-strength (50 mg niraparib/500 mg AA). The recommended dose of AKEEGA® is 200 mg niraparib and 1,000 mg AA daily.2About abiraterone acetateAbiraterone acetate (AA) is an orally administered androgen biosynthesis inhibitor. In the EEA, AA is indicated with prednisone or prednisolone for the treatment of newly diagnosed high risk mHSPC in adult men in combination with androgen deprivation therapy (ADT); the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated; and the treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.18Janssen-Cilag International NV currently market AA as ZYTIGA®.18About Metastatic Castration-Resistant Prostate CancermCRPC characterises cancer that no longer responds to ADT and has spread to other parts of the body.20 The most common metastatic sites are bones, followed by the lymph nodes, liver and lungs.21 Prostate cancer is the most common cancer in men in Europe.4 In 2020, more than one million men around the world were diagnosed with prostate cancer.22 Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time.10,11,12,13About MAGNITUDEMAGNITUDE (NCT03748641) is a Phase 3 randomised, double-blind, placebo-controlled, multicentre clinical study evaluating the safety and efficacy of the combination of niraparib and AA and predniso(lo)ne (AAP) for patients with mCRPC (n=765), with or without certain HRR gene alterations and who have not received prior therapy for mCRPC except for standard of care, next-generation androgen receptor inhibitors and up to four months of AAP.14,15 The study includes patients with (HRR biomarker [BM] positive; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM negative), who were randomised 1:1 to receive niraparib 200 mg once daily plus AAP or placebo plus AAP.15,16 A total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations.15,16 Additionally in an open-label cohort of HRR-positive patients, all patients received the DAT formulation of niraparib and AA plus prednisone.16 The primary endpoint of the MAGNITUDE trial is radiographic progression-free survival (rPFS) assessed by blinded independent central review.15,16 Secondary endpoints include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression and overall survival.15,16About the Janssen Pharmaceutical Companies of Johnson & JohnsonAt Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.Learn more at www.janssen.com/emea/. Follow us at www.twitter.com/JanssenEMEA for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag GmBH and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.*Professor Gerhardt Attard has served as a consultant to Janssen; he has not been paid for any media work.Cautions Concerning Forward-Looking StatementsThis 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 niraparib. 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 Pharmaceutica NV, Janssen-Cilag GmBH, Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies 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; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; 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 January 1, 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 www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.###References[1] Merseburger AS, et al. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist. 2013;18(5):558-567.[2] Beer TM, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–433.[3] Sumanasuriya S & De Bono J. Treatment of Advanced Prostate Cancer—A Review of Current Therapies and Future Promise. Cold Spring Harb Perspect Med. 2018;8(6):a030635.[4] Scott RJ, et al. Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021;12(16):1600-1614.[5] Abida W, et al. Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making. JCO Precis Oncol. 2017;2017:PO.17.00029.[6] Shore N, et al. Systematic Literature Review of the Epidemiology of Advanced Prostate Cancer and Associated Homologous Recombination Repair Gene Alterations. The Journal of Urology. 2021;205(4):977–986.[7] Castro E, et al. PROREPAIR-B: A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2019;37(6):490-503.[8] Cavanagh H, & Rogers KM. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary cancer in clinical practice. 2015;13(1):16. https://doi-org.libproxy1.nus.edu.sg/10.1186/s13053-015-0038-x[9] Messina C. et al. BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications. Journal of Oncology. 2020. 4986365.[10] Na R, et al. Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. European Urology. 2017;71(5):740–747.[11] Clinicaltrials.gov. A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE). Available at: https://clinicaltrials.gov/ct2/show/NCT03748641. Last accessed: April 2023.[12] Efstathiou E, et al. Niraparib With Abiraterone Acetate and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer and Homologous Recombination Repair Gene Alterations: Second Interim Analysis of MAGNITUDE. Poster presentation, 2023 ASCO GU Annual Meeting. February 16, 2023.[13] Chi N, et al. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023. Doi: https://doi. org/10.1200/JCO.22.01649.[14] European Medicines Agency. Zejula (niraparib) Summary of Product Characteristics. February 2023. Available at: Zejula, INN-niraparib; (europa.eu) Last accessed: April 2023.[15] European Medicines Agency. Zytiga (abiraterone acetate) Summary of Product Characteristics. June 2022. https://www.ema.europa.eu/en/documents/product-information/zytiga-epar-product-information_en.pdf. Last accessed: April 2023.[16] JnJ.com. Janssen Submits New Drug Application to the U.S. Food and Drug Administration Seeking Approval of Niraparib and Abiraterone Acetate Dual-Action Tablet, Plus Prednisone, as a First-Line Targeted Treatment for Patients with Metastatic Castration-Resistant Prostate Cancer with BRCA Gene Mutations. Available at: https://www.jnj.com/janssen-submits-new-drug-application-to-the-u-s-food-and-drug-administration-seeking-approval-of-niraparib-and-abiraterone-acetate-dual-action-tablet-plus-prednisone-as-a-first-line-targeted-treatment-for-patients-with-metastatic-castration-resistant-prostate-cancer-with-brca-gene-mutations. Last accessed: April 2023.[17] Clinicaltrials.gov. A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration Sensitive Prostate Cancer (mCSPC) (AMPLITUDE). Available at: https://clinicaltrials.gov/ct2/show/NCT04497844. Last accessed: April 2023.[18] Gsk.com. GSK completes acquisition of TESARO, an oncology focused biopharmaceutical company. Available at: https://www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-of-tesaro-an-oncology-focused-biopharmaceutical-company/. Last accessed: April 2023.[19] Johnsonandjohnson.gcs-web.com. Janssen Enters Worldwide Collaboration and License Agreement with TESARO, Inc., for Niraparib in Prostate Cancer. Available at: https://johnsonandjohnson.gcs-web.com/news-releases/news-release-details/janssen-enters-worldwide-collaboration-and-license-agreement. Last accessed: April 2023.[20] Urology Care Foundation. Metastatic Castration-Resistant Prostate Cancer (mCRPC): What You Should Know. Available at: https://www.urologyhealth.org/documents/Product-Store/English/mCRPC-What-You-Should-Know-Fact-Sheet.pdf. Last accessed: April 2023.[21] Gandaglia G, et al. Distribution of metastatic sites in patients with prostate cancer: A population-based analysis. Prostate. 2014;74(2):210-216.[22] Leith A et al. Real-World Treatment Patterns in Metastatic Castration-Resistant Prostate Cancer Across Europe (France, Germany, Italy, Spain, and the United Kingdom) and Japan. Advances in Therapy. 2022;39(5):2236-2255.

ART0380 demonstrated a tolerable and manageable safety profile, with monotherapy clinical activity in tumors predicted to be sensitive to ATR inhibition in Phase 1 dose escalation First of three Phase 2 solid tumor expansion cohorts evaluating ART0380 as a monotherapy and in combination with chemotherapy Initial Phase 2 data in patients with platinum resistant ovarian cancer expected in 1H 2025 CAMBRIDGE, United Kingdom and NEW YORK, Feb. 09, 2023 (GLOBE NEWSWIRE) -- Artios Pharma Limited (Artios), a clinical-stage biotech company pioneering the development of novel small molecule therapeutics that target the DNA damage response (“DDR”) process in order to treat patients with a broad range of cancers, announces the initiation of a randomized, Phase 2 expansion cohort in the ongoing Phase 1/2 trial evaluating its ataxia telangiectasia and Rad3-related (“ATR”) Inhibitor, ART0380, in combination with gemcitabine for the treatment of platinum resistant ovarian cancer. The initiation of the Phase 2 trial follows the successful Phase 1 dose escalation demonstrating a favorable safety and tolerability profile, clinical activity, and preferred pharmacokinetics with ART0380 in advanced solid tumors. The recommended Phase 2 dose of ART0380 monotherapy has been defined for both intermittent and continuous daily dosing schedules together with the regimen of ART0380 in combination with gemcitabine. Clinically active RECIST confirmed responses occurred across doses and in tumors harboring DDR deficiencies as predicted through Artios’ DcoDeR platform. Dr. Niall Martin, Chief Executive Officer at Artios, said: “This is the first of three proof of concept Phase 2 studies planned to evaluate our potentially best-in-class ATR inhibitor, ART0380, that has demonstrated a favorable safety and tolerability pro clinical activity in the Phase 1 dose escalation. We are delighted to be collaborating with ovarian cancer experts at GEICO in Spain on this important study that will help bolster our understanding of the therapeutic potential of ART0380 and further inform our clinical development strategy. We look forward to initial Phase 2 data expected in the first half of 2025.” Antonio Gonzalez-Martin, MD, PhD, President and Founding member of the Spanish Ovarian Cancer Research Group (GEICO), Principal Investigator for the trial, said: “Ovarian cancer continues to be a difficult to treat cancer that ultimately leads to relapse. We are excited to collaborate with Artios to help bring an ATR targeted therapy with the potential to be highly effective in patients with platinum-resistant disease who are in much need of innovative treatment options. The favorable pharmacokinetic pro combination with DNA damaging agents offers the potential of a new treatment option for patients with platinum resistant ovarian cancer. We at GEICO are looking forward to offering this novel treatment approach to our patients in the trial.” The ongoing global, open-label, multi-center, Phase 1/2 study is investigating the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of ART0380 (GEICO-114-O trial) as a monotherapy or in combination with gemcitabine or irinotecan. The randomized, Phase 2 portion is designed to evaluate intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles in patients with high grade serous ovarian, primary peritoneal or fallopian tube carcinoma. The Phase 2 expansion in combination with gemcitabine is expected to enroll up to 60 patients and will be conducted at multiple oncology centers across the United States and Spain. ART0380 is a potent, selective, oral inhibitor of ATR, a master regulator of DNA replication stress response. ART0380 is being developed as an oral anti-cancer agent for the treatment of cancers that harbor defects in DNA repair and in combination with agents including those that cause DNA damage. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was jointly developed as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division. For more information, please contact: Investor Contact: Abid Ansari, Chief Financial Officer E: aansari@artios.com Media Contact: LifeSci Advisors Ligia Vela Reid E: lvela-reid@lifesciadvisors.com About Artios Artios is on a mission to kill cancer by exploiting DNA damage repair (DDR) responses that are leveraged by cancer cells to promote their survival. Our specialized DcoDeR platform integrates Artios’ leadership capabilities, expertise and experience in DNA damage biology and drug discovery to systematically discover and develop medicines targeting the totality of the DDR. We have built an extensive DDR focused pipeline designed to address areas of high unmet needs across solid tumour indications including our ATR inhibitor, ART0380, and our Polθ inhibitor, ART4215, as a monotherapy and with combination treatments. Together with our world-class strategic partnerships with Merck KGaA and Novartis, and research collaborations with premiere institutions like Cancer Research UK, The Institute of Cancer Research, The Netherlands Cancer Institute, and the Crick Institute we are pioneering validated approaches to DDR drug discovery. Visit our website at for more information about the company and our pipeline. About ART0380 ART0380 is a potential best-in-class oral, highly potent, and selective ATR inhibitor. Ataxia telangiectasia and Rad3-related (ATR) is a master regulator of DNA replication stress response that promotes cell death by destabilizing replication forks, inducing DNA damage, or inhibiting checkpoint activation. ART0380 has broad clinical potential and is being investigated alone and in combination with other targeted therapies, chemotherapies or radiosensitizer opportunities in DDR deficient and high replication stress tumors. In a completed Phase 1a dose escalation study, ART0380 demonstrated RECIST confirmed responses, a favorable safety and tolerability profile, and a favorable PK profile. About the DcoDeR platform Artios has developed a specialized DcoDeR (“Decoding the DNA Damage Response”) platform which exploits its expertise and experience in DNA damage biology and drug discovery to systematically discover and develop medicines targeting the totality of the DDR. Our world class DNA damage response discovery platform allows us to understand disease biology, identify novel targets, develop new medicines, and select and treat patients who will benefit most. DcoDeR is being leveraged in ongoing research collaborations and licensing agreements with Merck KGaA to identify novel DDR nuclease inhibitors and with Novartis to identify DDR targets to use in combination with radioligand therapies. About GEICO The Spanish Ovarian Cancer Research Group (GEICO) is a non-profit organization, whose main purposes are to promote and develop research, training, and education in Gynecological Cancer. GEICO is a leader in clinical and translational research, particularly ovarian cancer. It currently enjoys international prestige and is an active member of the Gynecologic Cancer InterGroup (GCIG) and the European Network of Gynecological Oncological Trial Groups (ENGOT). It is currently made up of more than 300 experts working in around 130 hospitals throughout Spain. Since its constitution in 1999, GEICO has participated in more than 100 research projects and is highly committed to the fight against this disease. Visit our website at for more information about the group and its activities.

The PRIMA study, presented in a Presidential Symposium at the 2019 European Society for Medical Oncology congress and simultaneously published in The New England Journal of Medicine, demonstrates that niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall study population when compared to placebo Importantly women in both the HR-deficient ('HRD positive') and HR-proficient ('HRD negative') subgroups experienced a clinically meaningful and statistically significant benefit LONDON, Sept. 28, 2019 /PRNewswire/ -- GlaxoSmithKline plc (LSE/NYSE: GSK) today announced results from PRIMA (ENGOT-OV26/GOG-3012), the Phase 3 randomised, double-blind, placebo-controlled study of Zejula (niraparib) as a maintenance therapy in women with first-line ovarian cancer following a response to platinum-based chemotherapy. Niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population (PFS, HR 0.62; 95% CI, 0.50–0.75; p<0.001). These results were driven by a clinically meaningful reduction in risk of progression in women with: BRCA mutation tumours (risk reduction of 60%, HR 0.40 (95% CI, 0.27–0.62) p<0.001). HR-deficient BRCA wild type tumours (risk reduction of 50%, HR 0.50 (95% CI, 0.30–0.83), p=0.006). HR-proficient tumours (risk reduction of 32%, HR 0.68 (95% CI, 0.49–0.94), p=0.020). The PRIMA study enrolled patients with a response to their first-line treatment with platinum-based chemotherapy including those with high risk of disease progression, a population with high unmet need and previously under-represented in first-line ovarian cancer studies. Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Ovarian cancer is the eighth most commonly occurring cancer in women worldwide and women with this devastating disease have a five-year survival rate of less than 50%. PRIMA is a landmark study as we believe these data have the potential to fundamentally change how women with ovarian cancer are treated." In an interim analysis of overall survival (OS), niraparib also demonstrated an encouraging trend toward improvement in OS relative to placebo. A pre-planned interim analysis of OS numerically favoured niraparib in the overall population (HR 0.70; 95% CI 0.44-1.11). In the HR-deficient subgroup, 91% of women on niraparib were alive at 24 months vs. 85% for placebo (HR=0.61; 95% CI, 0.27-1.40). These data are not yet mature, and the significance is not fully known. The OS interim analysis also showed 81% of women receiving niraparib in the HR-proficient subgroup were alive at 24 months vs. 59% of women receiving placebo (HR=0.51; 95% CI, 0.27-0.97). Dr. Antonio Gonzalez, co-director, department of medical oncology, Clinica Universidad de Navarra, and Primary Investigator for PRIMA said: "The PRIMA study demonstrated the importance of maintenance therapy and the benefit that niraparib provided to women with ovarian cancer. I believe that niraparib monotherapy after surgery and platinum-based chemotherapy could be an important new treatment option for patients." Niraparib is not currently approved in the first-line ovarian cancer maintenance setting. GSK will share these data with the relevant health authorities and is on track to the end of the year. The safety pro in PRIMA did not differ from the established safety profile. The most common grade 3 or higher adverse events with niraparib included anaemia (31%), thrombocytopenia (29%), and neutropenia (13%). Implementation of an individualised dosing regimen based on body weight and/or platelet count reduced the incidence of haematological treatment-emergent adverse events. No new safety signals were identified. Validated patient reported outcomes indicate quality of life was similar between the niraparib and placebo treatment arms. Niraparib is marketed in the United States and Europe under the trade name Zejula®. About PRIMA PRIMA is a double-blind, randomised Phase 3 study designed to evaluate niraparib versus placebo in first-line Stage III or IV ovarian cancer patients. The study assessed the efficacy of niraparib as maintenance treatment, as measured by progression free survival. Patients with a response to first-line platinum chemotherapy were randomised 2:1 to niraparib or placebo. The trial was amended to include an individualised niraparib starting dose of 200 mg once-daily in patients with baseline weight <77kg and/or platelet count <150K/μL and 300 mg in all other patients. About Zejula (niraparib) Niraparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in three pivotal trials. GSK is building a robust niraparib franchise by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes a Phase 3 trial as first-line monotherapy maintenance treatment in patients with first-line ovarian cancer (the PRIMA trial), a Phase 3 study as a first-line triplet maintenance treatment in ovarian cancer (FIRST), a Phase 3 trial for the treatment of patients with germline BRCA-mutated, metastatic breast cancer (the BRAVO trial), and a Phase 2 study of niraparib combined with bevacizumab maintenance treatment in advanced ovarian cancer (OVARIO). Several combination studies are also underway, including trials of niraparib plus pembrolizumab in metastatic, triple-negative breast cancer and advanced, platinum-resistant ovarian cancer (the TOPACIO trial). Janssen Biotech has licensed rights to develop and commercialise niraparib specifically for patients with prostate cancer worldwide, except in Japan. Important Safety Information for ZEJULA Myelodysplastic Syndrome/Acute Myeloid Leukaemia (MDS/AML), including some fatal cases, was reported in 1.4% of patients receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all clinical studies. The duration of ZEJULA treatment in patients prior to developing MDS/AML varied from <1 month to 2 years. All patients had received prior chemotherapy with platinum and some had also received other DNA damaging agents and radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed. Haematologic adverse reactions (thrombocytopenia, anaemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anaemia and neutropenia were reported in 29%, 25%, and 20% of patients receiving ZEJULA, respectively. Discontinuation due to thrombocytopenia, anaemia, and neutropenia occurred, in 3%, 1%, and 2% of patients, respectively. Do not start ZEJULA until patients have recovered from haematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically thereafter. If haematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a haematologist for further investigations. Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in Trial 1, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary. Based on its mechanism of action, ZEJULA can cause foetal harm. Advise females of reproductive potential of the potential risk to a foetus and to use effective contraception during treatment and for 6 months after receiving their final dose. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose. In clinical studies, the most common adverse reactions (Grades 1-4) in ≥10% of patients included: thrombocytopenia (61%), anaemia (50%), neutropenia (30%), leukopenia (17%), palpitations (10%), nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), mucositis/stomatitis (20%), diarrhoea (20%), dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased appetite (25%), urinary tract infection (13%), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (10%), myalgia (19%), back pain (18%), arthralgia (13%), headache (26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety (11%), nasopharyngitis (23%), dyspnoea (20%), cough (16%), rash (21%) and hypertension (20%). Common lab abnormalities (Grades 1-4) in ≥25% of patients included: decrease in haemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%). About Ovarian Cancer Approximately 300,000 women are diagnosed with ovarian cancer each year. Ovarian cancer is the eighth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10% when treated with chemotherapy. GSK in Oncology GSK is focused on maximising patient survival through transformational medicines. GSK's pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination. About GSK GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit . 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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018. 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