On January 12, 2018 AstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the US and Canada) reported that the US Food and Drug Administration (FDA) has approved Lynparza (olaparib), for use in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting (Press release, AstraZeneca, JAN 12, 2018, View Source [SID1234523071]). Patients with hormone receptor positive (HR+) breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Patients are selected for therapy based on an FDA-approved companion diagnostic from Myriad Genetics.

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit, AstraZeneca, said: "This new approval for Lynparza makes it the first and only PARP inhibitor approved in metastatic breast cancer, and the only PARP inhibitor approved beyond ovarian cancer. This is significant for breast cancer patients, as the identification of BRCA status, in addition to hormone receptor and HER2 status, becomes a potentially critical step in the management of their disease."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories said: "This additional approval for Lynparza represents an important advance for women with HER2-negative metastatic breast cancer with a germline BRCA mutation, which is a difficult-to-treat cancer. Moreover, this approval adds further impetus to our important collaboration with AstraZeneca in developing cancer therapies."

The approval was based on data from the randomised, open-label, Phase III OlympiAD trial which investigated Lynparza versus physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine). In the trial, Lynparza significantly prolonged progression-free survival (PFS) compared with chemotherapy, and reduced the risk of disease progression or death by 42% (HR 0.58; 95% CI 0.43-0.80; P=0.0009 median 7.0 vs 4.2 months). Patients with measurable disease taking Lynparza (n=167) experienced an objective response rate of 52% (95% CI 44-60), double the response rate for those in the chemotherapy arm (n=66) which was 23% (95% CI 13-35). Additionally, patients experienced a confirmed complete response rate of 7.8% for Lynparza compared to 1.5% for the chemotherapy arm. The data from the OlympiAD trial can be found in the June 2017 issue of the New England Journal of Medicine.

Susan M. Domchek, Executive Director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania, and a national leader on the OlympiAD trials, said: "Patients diagnosed with BRCA-related metastatic breast cancer are often younger than other breast cancer patients, and their disease is often much more aggressive and difficult to treat. While there is currently no cure for metastatic breast cancer, today’s approval offers a new, targeted option that may help to delay disease progression for these patients."

The most common adverse reactions (≥20%) in the OlympiAD trial of patients who received Lynparza were nausea (58%), anaemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhoea (21%), and headache (20%). The percentage of patients who discontinued treatment in the Lynparza arm was 5% compared to the chemotherapy arm which was 8%.

This is the third indication approved for Lynparza in the US, where it has been used to treat nearly 4,000 advanced ovarian cancer patients. Lynparza has the broadest clinical development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to deliver Lynparza as quickly as possible to more patients across multiple settings, including breast, ovarian, prostate and pancreatic cancers.

Sustainable and Ongoing Externalisation Revenue
Under the oncology collaboration with Merck, announced in July 2017, AstraZeneca is potentially eligible for more than $6 billion of future Sustainable and Ongoing Externalisation Revenue in the form of sales-related and approval-related payments in addition to option payments until 2019. Following this new approval for Lynparza, AstraZeneca will receive $70 million in Sustainable and Ongoing Externalisation Revenue.

About OlympiAD
OlympiAD is a randomised, open-label, multicentre Phase III trial assessing the efficacy and safety of Lynparza tablets (300 mg twice daily) compared to physician’s choice of chemotherapy in 302 patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are confirmed or suspected to be deleterious. The international trial was conducted in 19 countries across Europe, Asia, North America and South America.

Patients in the OlympiAD trial had HER2-negative gBRCA1- or gBRCA2-mutated breast cancer, which was HR+ or triple negative, and received Lynparza for metastatic disease. Approximately half of the patients in the Lynparza and chemotherapy arm of the trial were HR+ (n=152), and approximately half were triple negative (n=150). Among the 205 patients treated with Lynparza, the median age was 44 years (range: 22 to 76). Before enrolment, patients had prior treatment with an anthracycline (unless contraindicated) and a taxane chemotherapy either in the neoadjuvant, adjuvant or metastatic setting and no more than two prior lines of chemotherapy for metastatic disease. Hormone receptor-positive patients had received at least one endocrine medicine or were not eligible for endocrine medicines. Prior treatments with endocrine medicines were not counted as prior lines of chemotherapy.

The primary endpoint of the trial was PFS as measured by a Blinded Independent Central Review. Secondary endpoints included overall survival, time to second progression or death, objective response rate, and effect on health-related quality of life.

About Metastatic Breast Cancer (MBC)
Three main receptors drive tumour growth in breast cancer: progesterone receptors (PR), estrogen receptors (ER) and HER2 receptors. A patient’s breast cancer will test either negative or positive for these three receptors. If a tumour tests positive for PR and/or ER, it is considered HR+. If a tumour tests negative for all three receptors, it is considered triple negative.

MBC is the most advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumour site to other parts of the body outside of the breast.

Despite the increase in treatment options during the past three decades, there is currently no cure for patients diagnosed with MBC and only 26.9% of patients survive five years after diagnosis. Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving, or at least maintaining, a patient’s quality of life.

It is estimated that in 2018, there will be approximately 155,000 women in the US living with MBC, and this number is projected to increase to approximately 160,000 by the year 2020.

About Germline BRCA Mutations
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About Lynparza (olaparib)
Lynparza is the first FDA-approved oral poly ADP-ribose polymerase (PARP) inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.

Lynparza is being investigated in a range of DDR-deficient tumour types and is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.

About the AstraZeneca and MSD Strategic Oncology Collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. The collaboration is based on increasing evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumour types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as a monotherapy. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On January 12, 2018 Ipsen (Euronext: IPN; ADR: IPSEY) reported the appointment of Richard Paulson as Executive Vice-President and Chief Executive Officer of Ipsen North America, responsible for all commercial operations throughout the region. Mr Paulson will assume oversight of all areas supporting the North American business effective from February 5th (Press release, Ipsen, JAN 12, 2018, View Source [SID1234523076]). The role reports directly to David Meek, CEO of Ipsen, and Mr Paulson will be a member of the Ipsen Executive Leadership Team. He joins Ipsen from Amgen where he most recently served as Vice-President and General Manager of the Oncology Business Unit.

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David Meek, Ipsen’s CEO, commented, "We are extremely delighted to welcome Richard to Ipsen, to drive the continued growth of our North American business and further our development as a leading biopharma company focused on innovation and specialty care. Richard brings a wealth of great leadership experience, vision, and a track record of exceptional execution in leading and growing businesses, both in the US and internationally. He will bring great passion and energy to our work with patients."

During a 10-year career at Amgen, Richard Paulson held a number of positions in the company, including General Manager, Central and Eastern Europe, and subsequently General Manager Germany, before assuming leadership positions in Amgen’s Oncology Business Unit. Prior to joining Amgen, he held international positions in general management, marketing and market access with Pfizer. He also served in a number of sales and marketing roles with increasing seniority for GlaxoWellcome in Canada. He holds an MBA from the University of Toronto.

Richard Paulson added: "I am honored to join Ipsen at this time of rapid transformation and growth, as the company progresses in its evolution as a leading global biopharma company. Throughout my career, in markets around the world, I have been passionate about building and leading diverse, high-performing teams, and driving innovation for patients. I am extremely excited to join this dynamic company, with its clear mission and commitment to developing patient-focused solutions that put the patients’ needs first."

With the former President North America Cynthia Schwalm leaving Ipsen to pursue other interests, Ipsen would like to thank Cynthia for her many contributions to the growth of Ipsen’s North American business, and wishes her well in her future endeavors

On January 12, 2018 Halozyme Therapeutics Inc presented at the 36th Annual J.P. Morgan healthcare conference (Presentation, Halozyme, JAN 12, 2018, View Source [SID1234523105]).

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On January 12, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that the U.S. Food and Drug Administration (FDA) approved BRACAnalysis CDx for use as a companion diagnostic by healthcare professionals to identify patients with HER2-negative metastatic breast cancer who have a germline BRCA mutation and are candidates for treatment with the PARP inhibitor Lynparza (olaparib), marketed by AstraZeneca and Merck, known as MSD outside of the U.S. and Canada (Press release, Myriad Genetics, JAN 12, 2018, View Source [SID1234523106]). BRACAnalysis CDx is the first and only FDA-approved test for use in this indication.

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"This important advance underscores the need for patients with HER2-negative metastatic breast cancer to know their BRCA status with an FDA approved test to help ensure that they will receive the best available therapy," said Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetics. "As shown in the OlympiAD study, Myriad’s BRACAnalysis CDx test was proven to accurately identify those patients who had a germline BRCA mutation and may benefit from Lynparza."

The approval also adds to the body of knowledge about the clinical use and value of companion diagnostics to enable personalized medicine for people with cancer.

"We congratulate AstraZeneca and Merck on obtaining FDA approval of Lynparza for patients with metastatic breast cancer, which is the first approval of a PARP inhibitor outside of ovarian cancer. As the pioneers in identifying likely responders to PARP inhibitors, we are excited to broaden the use of BRACAnalysis CDx as the companion diagnostic for this important new indication," said Mark C. Capone, president and CEO, Myriad Genetics. "We will be actively working with all stakeholders to raise awareness so that patients can be immediately tested to determine if they are likely to benefit from Lynparza."

Approximately one in eight women are diagnosed with breast cancer in the United States, and one-third are diagnosed with or will progress to the metastatic stage of the disease.

"There are more than 155,000 patients with metastatic breast cancer in the United States, and we estimate that 125,000 do not know their BRCA status," said Lancaster. "This new FDA approval of BRACAnalysis CDx for patients with metastatic breast cancer significantly expands the population who can access BRCA testing and potentially benefit from PARP inhibition therapy."

The collaboration with AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib began in 2007. The new metastatic breast cancer indication is the second FDA approval of BRACAnalysis CDx for use in conjunction with Lynparza. In Dec. 2014, Myriad received FDA approval for BRACAnalysis CDx to help identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic and was the first-ever laboratory developed test approved by the FDA.

About BRACAnalysis CDx

BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying breast and ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants, who are or may become eligible for treatment with Lynparza (olaparib). Detection of deleterious or suspected deleterious germline BRCA variants by the BRACAnalysis CDx test in ovarian cancer patients is also associated with enhanced progression-free survival (PFS) from Zejula (niraparib)maintenance therapy. This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108. Learn more at: View Source

About Lynparza

Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumor DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved in the United States 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 and for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Patients are selected for therapy based on Myriad’s FDA-approved companion diagnostic. It is also approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

In July 2017, AstraZeneca and Merck announced a global strategic oncology collaboration to jointly co-develop and co-commercialize Lynparza.

On January 11, 2018 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that the European Medicines Agency (EMA) has granted Orphan Drug Designation to pracinostat, an investigational drug candidate currently in a Phase 3 study in combination with azacitidine for the treatment of acute myeloid leukemia (AML) in adult patients unfit to induction chemotherapy (Press release, MEI Pharma, JAN 11, 2018, View Source [SID1234523054]).

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The orphan drug designation is based on the scarcity of treatments for patients suffering from AML and on positive Phase 2 study results (see below) that were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, in December 2016.

The EMA orphan drug designation is a status assigned to a medicine intended for use against a rare condition in the European Union (prevalence of the condition in the European Union must not be more than 5 in 10,000). The designation allows pharmaceutical companies to benefit from incentives offered by the EU to develop a medicine for the treatment, prevention or diagnosis of a disease that is life threatening or a chronically debilitating rare disease. These include 10 years of market exclusivity once approved, alongside a range of other regulatory advantages.

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, commented: "Helsinn is pleased with the decision of the EMA to grant orphan drug designation to pracinostat. This decision encourages us to continuously dedicate significant resources to accelerate our clinical trial program, with a goal of helping patients who are fighting rare and difficult-to-treat diseases, such as AML and, at present, have very few treatment options. Following the positive Phase 2 clinical trials of pracinostat for patients with AML, Helsinn has recently initiated the Phase 3 program."

"This designation from the EMA recognizes the potential that pracinostat holds in addressing a significant unmet need for those suffering with AML," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "This represents another important milestone in the global development strategy for pracinostat."

1st patient randomized in Phase 3 trial:

In August of 2017, Helsinn and MEI Pharma announced that the first patient has been dosed in the pivotal Phase 3 study of the investigational agent pracinostat in combination with Azacitidine in adults with newly diagnosed acute myeloid leukemia (AML) who are unfit to receive intensive induction chemotherapy. The primary endpoint of the study is overall survival. Secondary endpoints include, among others, morphologic complete remission (CR) rate, cytogenetic complete remission and complete remission without minimal residual disease.

Phase 2 study results for pracinostat for the treatment of AML:

Results from a Phase 2 open-label, single-arm, multicenter study of pracinostat and azacitidine in 50 patients aged ≥ 65 years with newly diagnosed AML not eligible for induction chemotherapy showed a median overall survival of 19.1 (95%CI: 10.0-26.5) months, one-year survival of 62% and a CR rate of 42%. These results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.

About AML
AML is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 21,380 new cases and 10,590 deaths from AML in the U.S. for 2017; the average age of a patient with AML is about 67 years. According to the Surveillance of Rare Cancers in Europe project, the incidence of AML in Europe is 3.7 per 100,000. There are currently no drugs approved in the U.S. to treat AML in patients who are unfit for intensive induction chemotherapy, though hypomethylating agents are recommended by the National Comprehensive Cancer Network (NCCN) guidelines. In the EU, Azacitidine is approved for the treatment of adult patients who are not eligible for hematopoietic stem cell transplant (HSCT) with AML with >30% marrow blasts according to the World Health Organization (WHO) classification, and decitabine is approved the treatment of adult patients with newly diagnosed de novo or secondary AML, according to the World Health Organisation (WHO) classification, who are not candidates for standard induction chemotherapy.

About Pracinostat
Pracinostat is an oral histone deacetylase (HDAC) inhibitor that is in late-stage clinical development. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with Azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. Under the terms of the agreement, Helsinn is granted a worldwide exclusive license to develop, manufacture and commercialize pracinostat, and is primarily responsible for funding its global development and commercialization. Pracinostat is under clinical investigation and has not been approved by any health authority worldwide.