On June 1, 2018 LabCorp (NYSE: LH), a leading global life sciences company, and Unilabs, a leading European provider of clinical laboratory testing and medical diagnostic imaging services, reported a strategic collaboration to provide expanded global development and delivery of companion diagnostics (Press release, LabCorp, JUN 1, 2018, View Source;p=RssLanding&cat=news&id=2352738 [SID1234527046]). This collaboration broadens the network of laboratories used by biopharmaceutical companies to support companion diagnostic development and commercialization. The purpose of the collaboration is to expand access to commercialization channels for companion diagnostics in North America and Europe, and accelerate the adoption of companion diagnostics. The companies will use globally harmonized processes to simplify the technical, regulatory and clinical complexities associated with these critical assays. The companies expect the first application of these processes will be in oncology, particularly immuno-oncology.

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This press release features multimedia. View the full release here: View Source

LabCorp, an established leader in the development and commercialization of companion diagnostics, processes more than 2.5 million patient specimens per week, collected from clinician offices and hospitals and via its own network of nearly 2,000 patient service centers, more than 5,000 in-office phlebotomists and a growing retail presence. Unilabs, a European leader, has more than 230 laboratories in 15 countries and 350 customer service locations, and processes more than 188 million diagnostic tests each year.

The collaboration will initially focus on the commercial availability of assays that have been developed and validated both analytically and clinically by LabCorp and Covance, LabCorp’s drug development business. Terms of the agreement have not been disclosed.

"Companion diagnostics are an essential component of precision medicine, enabling physicians to identify the patients who are most likely to benefit from targeted and novel therapies," said David P. King, LabCorp chairman and CEO. "With this collaboration, we are capitalizing on the scientific and operational strengths of two leaders in companion diagnostics to benefit biopharmaceutical clients who need global solutions for precision medicine, with the ultimate goal of improving health and improving lives for patients around the world."

"Our collaboration with LabCorp addresses the need for global harmonization and combined capabilities, including scientific expertise, operational excellence and timely availability of high-quality companion diagnostic services," said Unilabs CEO, Jos Lamers. "With our extensive laboratory network and geographical footprint, we enable clients to accelerate their precision medicine development and commercialization efforts. Our combined ability to bridge the time gaps between development phase and drug approval, and to national reimbursement, by offering a centralized laboratory testing facility, gives our respective customers the advantage of early adoption of their drug. The intimate knowledge of local testing standards, regulatory and quality requirements and navigating logistical challenges will ensure instant access to high-quality testing. This facilitates embracing of a new test in the clinic thereby removing critical barriers for a new treatment."

On June 1, 2018 Ruth Plummer, MD, PhD, FRCP, reported it will present an abstract describing the first-in-human Phase 1 study of 2X-121, an investigational PARP 1/2 and tankyrase 1/2 inhibitor, as monotherapy in patients with advanced solid tumors (Press release, 2X Oncology, JUN 1, 2018, View Source [SID1234527030]).

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Abstract Title: First-in-human phase 1 study of the PARP/tankyrase inhibitor 2X-121 (E7449) as monotherapy in patients with advanced solid tumors and validation of a novel drug response predictor (DRP) mRNA biomarker.

Abstract No.: 2505

Date: June 1, 2018

Time: 4:09pm CDT

Location: S406

On June 1, 2018 Pfizer Inc. (NYSE:PFE) reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for TRAZIMERA, a potential biosimilar to Herceptin (trastuzumab), for the treatment of HER2 overexpressing breast cancer and HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.1 (Press release, Pfizer, JUN 1, 2018, View Source [SID1234527047]).

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"Pfizer is extremely proud to offer expanded biologic treatment options for patients by bringing more affordable, life changing biosimilar medicines to market, and today’s positive recommendation from the CHMP marks one more step forward. TRAZIMERA has the potential to help many patients with HER2 overexpressing cancers across Europe and, if approved, would help address the evolving needs of healthcare systems, physicians, payers and patients, "said Amrit Ray, MD, MBA, Global President, Research & Development, Pfizer Essential Health.

The regulatory submission is supported with a comprehensive data package and totality of evidence demonstrating a high degree of similarity to the originator product. This includes results from the primary REFLECTIONS B327-02 clinical comparative study, which demonstrated clinical equivalence and found no clinically meaningful differences between TRAZIMERA and Herceptin in patients with first line HER2 overexpressing metastatic breast cancer. As part of the REFLECTIONS clinical trial program for the proposed biosimilar trastuzumab, TRAZIMERA has been studied in nearly 500 patients and across more than 20 countries to date.2,3,4

"Many patients with breast and gastric cancers have an HER2 overexpression, which can correlate with poor outcomes and aggressive disease," said Dr. Mark Pegram, associate director for clinical research at the Stanford Comprehensive Cancer Institute, and director of the Breast Oncology Program at the Stanford Women’s Cancer Center.5,6 "With the availability of biosimilars like TRAZIMERA in Europe, oncologists will have additional treatment options to choose from, which potentially helps our patients have greater access to these medicines."

TRAZIMERA is Pfizer’s fourth7,8,9 biosimilar and first therapeutic oncology biosimilar to receive a positive CHMP opinion from the EMA. Pfizer’s biosimilars pipeline is progressing and consists of 11 distinct Pfizer and legacy Hospira biosimilar molecules in various stages of development.

Working together for a healthier world

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of June 1, 2018. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about TRAZIMERA, Pfizer’s proposed trastuzumab biosimilar, including its potential benefits, that involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical trial commencement and completion dates and regulatory submission dates, as well as the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate, regulatory authorities may not share our views and may require additional data or may deny approval altogether; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when applications for TRAZIMERA may be filed in any other jurisdictions; whether and when the European Commission may approve the pending application for TRAZIMERA in the EU and whether and when any such other applications for TRAZIMERA that may be pending (including the application pending with the FDA, for which the company received a complete response letter) or filed may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted and, if approved, whether TRAZIMERA will be commercially successful; intellectual property and/or litigation implications; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of TRAZIMERA; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2017 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.

On June 1, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported findings from an interim analysis of the Phase 3 iNNOVATE (PCYC-1127) study evaluating IMBRUVICA (ibrutinib) plus RITUXAN (rituximab) in previously untreated and relapsed/refractory patients with Waldenström’s macroglobulinemia (WM), a rare type of non-Hodgkin’s lymphoma (NHL) (Press release, AbbVie, JUN 1, 2018, View Source [SID1234527031]). At a median follow up of 26.5 months, the study successfully met its primary endpoint, demonstrating a significant improvement in progression-free survival (PFS) with ibrutinib plus rituximab compared to rituximab alone (30 month PFS rates were 82 percent versus 28 percent, respectively). Patients taking ibrutinib plus rituximab also experienced an 80 percent reduction in relative risk of disease progression or death than those only treated with rituximab (hazard ratio, 0.20; confidence interval: 0.11-0.38, P <0.0001). Additionally, the data found that the combination with ibrutinib provided reductions in infusion reactions associated with rituximab and immunoglobin M (IgM) flare.1

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These data were presented today in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (abstract #8003) and were simultaneously published in The New England Journal of Medicine. The data were also selected for the 2018 Best of ASCO (Free ASCO Whitepaper) Meetings. With the support of these positive findings, a supplemental New Drug Application (sNDA) to expand the use of IMBRUVICA as a combination therapy in WM was submitted to the U.S. Food and Drug Administration (FDA) for review. The Independent Data Monitoring Committee (IDMC) in late 2017 recommended unblinding iNNOVATE based on these positive findings.

"The iNNOVATE study provides further evidence of the potential clinical benefit of IMBRUVICA-based combination therapy in patients with Waldenström’s macroglobulinemia," said Thorsten Graef, M.D., Ph.D., Head of Clinical Development at Pharmacyclics LLC, an AbbVie company. "The data from this chemotherapy-free combination regimen suggests that patients with Waldenström’s macroglobulinemia, including those who are newly diagnosed, could have another beneficial therapeutic option in the future."

WM is a rare and incurable form of NHL with limited treatment options. There are about 2,800 new cases of WM in the U.S. each year.2 In January 2015, IMBRUVICA received FDA approval for all lines of treatment in WM and is the first and only FDA-approved therapy specifically indicated for this disease. IMBRUVICA has been available in the U.S. since 2013 and is FDA-approved for use in five B-cell blood cancers, as well as previously-treated chronic graft-versus-host disease. IMBRUVICA is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

"The iNNOVATE trial broadens our understanding about how to treat patients with WM, including those with certain subtypes or genomic abnormalities," said Dr. Meletios A. Dimopoulos, Professor and Chairman of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece and lead investigator of the iNNOVATE study.* "As a clinician, I’m hopeful that the data from iNNOVATE could potentially lead to a new option for treating this rare and incurable disease."

To view all IMBRUVICA company-sponsored or investigator-initiated studies being presented at ASCO (Free ASCO Whitepaper) 2018, please visit: View Source

Abstract #8001: Randomized phase 3 trial of ibrutinib/rituximab vs placebo/rituximab in Waldenström’s Macroglobulinemia
Oral presentation: Friday, June 1, 3:45pm CDT

In the iNNOVATE study, PFS occurred at a higher rate in patients treated with ibrutinib plus rituximab compared to rituximab alone, with PFS rates of 82% versus 28% at 30 months, respectively. Notably, ibrutinib plus rituximab exhibited longer duration of PFS in all relevant patient subgroups, including treatment-naïve, relapsed, and in patients with MYD88L265P and CXCR4WHIM mutations, versus rituximab. Patients taking ibrutinib plus rituximab also experienced an 80 percent reduction in relative risk of disease progression or death than those only treated with rituximab (median PFS, not reached [NR] vs 20.3 months; HR, 0.20; CI: 0.11-0.38, P <0.0001).

iNNOVATE is a Pharmacyclics-sponsored, placebo-controlled, double-blind, Phase 3 study, which evaluated relapsed/refractory and treatment-naïve WM patients (n=150) who were randomized to receive intravenous rituximab 375 mg/m2 once weekly for four consecutive weeks, followed by a second once-weekly for four consecutive weeks rituximab course after a three-month interval. All patients received either ibrutinib 420 mg or placebo once daily continuously until criteria for permanent discontinuation were met. The IRC-determined primary endpoint was PFS, with secondary objectives including overall response rate, hematological improvement measured by hemoglobin, time-to-next treatment (TTnT), overall survival (OS), and number of participants with adverse events (AEs) as a measure of safety and tolerability within each treatment arm.

Overall response rates and major response rates were significantly higher for ibrutinib plus rituximab versus rituximab (92% vs 47%; 72% vs 32% [both P <0.0001]). In addition, there was also an improvement in hemoglobin seen in patients treated with the combination versus rituximab (73% vs 41%, P <0.0001).

Of the patients on ibrutinib plus rituximab, 75% continued on treatment. Median TTnT was NR for ibrutinib plus rituximab and 18 months for rituximab (HR, 0.096; P <0.0001). The 30-month OS rates were 94% versus 92% in the two arms.

At the median time on treatment (ibrutinib plus rituximab, 25.8 months; rituximab plus placebo, 15.5 months,), grade 3 or higher treatment-emergent AEs occurred in 60% of patients treated with ibrutinib plus rituximab, versus 61% of patients treated with rituximab. Serious AEs occurred in 43% versus 33% of patients on ibrutinib plus rituximab vs rituximab. No fatal AEs occurred with ibrutinib plus rituximab and 3 with rituximab. Meaningful reductions in any grade IgM flare (8% vs 47%) and grade 3 or higher infusion reactions were observed (1% vs 16%) with ibrutinib plus rituximab.

About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that mainly works by blocking a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells as well as other serious, debilitating conditions.3 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.

IMBRUVICA is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host disease (cGVHD).4

IMBRUVICA was first approved for adult patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in adult CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for adult CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for adult patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for adult patients with previously treated CLL/SLL.
In January 2017, IMBRUVICA was approved for adult patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
In August 2017, IMBRUVICA was approved for adult patients with cGVHD that failed to respond to one or more lines of systemic therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.5 IMBRUVICA was one of the first medicines to receive FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with more than 130 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 100,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.
The mechanism for the bleeding events is not well understood.

IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding.

Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.

Monitor and evaluate patients for fever and infections and treat appropriately.

Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 13%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA.

Monitor complete blood counts monthly.

Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0 to 1% of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 0 to 6% of patients. These events have occurred particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac arrhythmias.

Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension: Hypertension (range, 6 to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA.

Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.

Second Primary Malignancies: Other malignancies (range, 3 to 16%) including non-skin carcinomas (range, 1 to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2 to 13%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.

Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (62%)*, neutropenia (61%)*, diarrhea (43%), anemia (41%)*, musculoskeletal pain (30%), bruising (30%), rash (30%), fatigue (29%), nausea (29%), hemorrhage (22%), and pyrexia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%)*, thrombocytopenia (16%)*, and pneumonia (10%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9 % (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%)*, pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).

Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.

*Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse reactions.

DRUG INTERACTIONS

CYP3A Inhibitors: Dose adjustment may be recommended.

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe baseline hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose.

On June 1, 2018 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported the National Institute for Health and Care Excellence (NICE) will make ZEJULA (niraparib), the first PARP inhibitor shown to be effective in patients with a BRCA mutation as well as those without a BRCA mutation, available to women in England and Wales with recurrent platinum-sensitive ovarian cancer via the Cancer Drugs Fund (CDF)1 (Press release, TESARO, JUN 1, 2018, View Source [SID1234527048]). NICE has recommended ZEJULA via the CDF for women with a BRCA mutation who have received two lines of chemotherapy and in women without a BRCA mutation who have received two or more lines of chemotherapy.

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"At TESARO, we continue to globalize our mission and bring transformative therapies to patients. We are pleased that NICE will now provide more women with recurrent ovarian cancer in England and Wales access to ZEJULA through the CDF," said Orlando Oliveira, Senior Vice President and General Manager, TESARO International. "Through close partnership with both NICE and NHS, TESARO can now offer ZEJULA as an option for second-line maintenance treatment, regardless of a patient’s BRCA status."

The CDF is a source of funding for cancer drugs in England, providing patients access to promising new oncology treatments while NHS England and NICE analyze any additionally requested data to inform a final reimbursement decision on a new treatment or indication. Overall survival data for ZEJULA are not yet available, and as a result NICE has recommended ZEJULA for use within the CDF while further data are collected2. Interim funding is provided via the CDF, giving patients access to the treatment through a managed access arrangement.

"Recurrent ovarian cancer is an aggressive form of cancer where a key goal of treatment is to keep women in remission and off chemotherapy for as long as possible – allowing them the best chance for a good quality of life," said Jonathan Ledermann, Professor of Medical Oncology at the University College London Cancer Institute. "ZEJULA offers the chance to delay this cancer from returning or progressing for months, and possibly years in some cases. It is a significant step forward. Crucially, this decision opens the door for many women who, until now, have not had the option of maintenance treatment with a PARP inhibitor."

About Ovarian Cancer
In the UK, ovarian cancer has the highest mortality rate of all gynecological cancers3. It has one of the highest incidence rates in Europe4 with survival rates among the lowest5. The rate of newly diagnosed cases of ovarian cancer in the UK is 16 per 100,000 of the population compared to the European average of 12.6 per 100,0005. Every year 4,100 women lose their lives to ovarian cancer – 11 women every day6.

The most common symptoms of ovarian cancer include abdominal or pelvic pain, bloating, difficulty eating, and urinary urgency, all of which are commonly associated with less serious conditions. 60% of women with ovarian cancer are diagnosed in an advanced stage7, when prognosis is poor. Although significant progress has been made in treatment of ovarian cancer, the disease recurs in approximately 85% of women with advanced ovarian cancer8, at which point it may be incurable9,10. Recurrent ovarian cancer is the sixth most common cause of cancer death among women and has the highest mortality rate of all gynecological cancers.

About ZEJULA (niraparib)
Niraparib is marketed in the United States and Europe under trade name ZEJULA. ZEJULA is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. In preclinical studies, ZEJULA concentrates in the tumor relative to plasma, delivering greater than 90% durable inhibition of PARP 1/2 and a persistent antitumor effect.

ZEJULA is approved in Europe as a 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 response (CR) or partial response (PR) to platinum-based chemotherapy. The approval was based on data from the clinically rigorous ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study of ZEJULA that enrolled 553 patients with recurrent ovarian cancer who had achieved either a PR or CR to their most recent platinum-based chemotherapy. ZEJULA is the first once-daily, oral poly (ADP-ribose) polymerase (PARP)1/2 inhibitor to be approved in Europe that does not require BRCA mutation or other biomarker testing.

The primary endpoint of the trial was progression free survival (PFS). Approximately two-thirds of study participants did not have germline BRCA mutations. Progression in the NOVA study was determined by a robust, unbiased, blinded central review to be the earlier of radiographic or clinical progression. ZEJULA significantly increased PFS in patients with or without germline BRCA mutations as compared to the control arm. Treatment with ZEJULA reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (hazard ration (HR) 0.27) and by 55% in patients without germline BRCA mutations (HR 0.45). The magnitude of benefit was similar for patients entering the trial with a PR or a CR.

The approved starting dose of ZEJULA is 300 milligrams once per day. According to the European summary of product characteristics (SmPC), in patients below 58 kilograms, a starting dose of 200 milligrams once per day may be considered. The most commonly administered dose of ZEJULA over the course of the Phase 3 NOVA clinical trial was 200 milligrams once per day, following dose modification. Further exploratory analyses of the NOVA study indicated that individual dose modification maintained efficacy and reduced the rate of new adverse events.11

ZEJULA (niraparib) Select Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) was reported in patients treated with ZEJULA in some clinical studies. Discontinue ZEJULA if MDS/AML is confirmed. Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients treated with ZEJULA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time.

Hypertension and hypertensive crisis have been reported in patients treated with ZEJULA. 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.

Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for six months after receiving the final dose. Because of the potential for serious adverse reactions in breastfed infants from ZEJULA, advise a lactating woman not to breastfeed during treatment with ZEJULA and for one month after receiving the final dose.