On February 14, 2019 Orion’s and Bayer’s reported that darolutamide plus androgen deprivation therapy (ADT) significantly extends metastasis-free survival with a favorable safety profile compared to placebo plus ADT in non-metastatic castration-resistant prostate cancer (Press release, Orion Biotechnology, FEB 14, 2019, View Source [SID1234533350]).

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Statistically significant improvement in metastasis-free survival (MFS), with a median MFS of 40.4 months with darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT (18.4 months).

Positive trend in overall survival with a 29% reduction in risk of death at interim analysis (P=0.045).

Incidence of treatment-emergent adverse events was similar for darolutamide plus ADT and placebo plus ADT.

Health-related quality of life was maintained.
First results from the Phase III ARAMIS trial with the androgen receptor antagonist darolutamide were presented in an oral presentation at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium and simultaneously published in The New England Journal of Medicine.
Abstract: 140 – ARAMIS

Results from the pivotal Phase III ARAMIS trial in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) showed a statistically significant improvement in metastasis-free survival (MFS) with darolutamide plus standard of care (ADT) compared to placebo plus ADT (HR=0.41, 95% CI 0.34-0.50; P<0.001). This translates to a 59 percent reduction in the risk of metastasis or death. The median MFS was 40.4 months in the darolutamide arm compared with 18.4 months for the placebo arm – an overall improvement in median MFS of 22 months.

A positive trend in overall survival (OS) was also observed (HR=0.71, 95% CI 0.50-0.99; P=0.045), and all other secondary endpoints demonstrated a benefit in favor of darolutamide. Importantly, the incidence of treatment-emergent adverse events (AEs) with greater than or equal to 5 percent frequency or of grade 3-5 was comparable between darolutamide and placebo arms; only fatigue occurred in more than 10 percent of patients (darolutamide plus ADT resulted in 12.1 percent versus 8.7 percent in patients with placebo plus ADT). Quality of life outcomes were similar between the treatment groups.

These data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco and published simultaneously in The New England Journal of Medicine.

"In addition to a benefit in MFS, a favorable safety profile is critical for these largely asymptomatic nmCRPC patients because treatment decisions can impact their overall well-being, prognosis, compliance with the treatment as well as other medications that are typical for this patient population. These data are exciting for the prostate cancer community; they not only show darolutamide’s significant efficacy in preventing the spread of prostate cancer, but also its favorable tolerability profile that, once approved, may allow patients to continue their day-to-day life without adding any burden," said Karim Fizazi, M.D., Ph.D., Professor of Medicine at the Institut Gustave Roussy, University of Paris Sud, France.

"Prostate cancer patients are still in need of treatments that are not only effective but also safe without adverse events that would compromise their quality of life. Orion is working hard to bring innovative treatments to cancer patients. With the positive results of ARAMIS trial we together with Bayer are one step closer of bringing darolutamide to patients and their treating physicians", said Christer Nordstedt, PhD, MD, Senior Vice President, Research and Development, Orion Corporation.

Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding the submission of new drug applications. Bayer has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for darolutamide in men with nmCRPC. Darolutamide is being developed jointly by Bayer and Orion Corporation.

Detailed study results

The MFS benefit observed with darolutamide was consistent across all subgroups of patients. In an interim analysis of OS, darolutamide showed a positive trend, with a 29 percent reduction in the risk of death (HR=0.71, 95% CI 0.50-0.99; P=0.045, median not reached).

In addition, darolutamide plus ADT demonstrated a significant benefit over placebo plus ADT for time to pain progression (40.3 months compared to 25.4 months; HR=0.65, 95% CI 0.53-0.79; P<0.001) and time to cytotoxic chemotherapy (median not reached compared to 38.2; HR=0.43, 95% CI 0.31-0.60; P<0.001). Another secondary endpoint, time to first symptomatic skeletal event (SSE), also demonstrated a benefit in favor of darolutamide (median not reached). Darolutamide extended progression-free survival (PFS) (36.8 months compared to 14.8 months; HR=0.38, 95% CI 0.32-0.45; P<0.001), with a 62 percent risk reduction of local progression, distant metastases or death.

Incidence of treatment-emergent AEs was similar between darolutamide and placebo; most AEs were grade 1 and 2 (55 percent with darolutamide plus ADT and 54 percent with placebo plus ADT). Compared to placebo plus ADT, darolutamide plus ADT did not increase rates of critical AEs including, but not limited to, seizures, falls, fractures, rash, cognitive disorder, mental impairment or hypertension. Patients with a history of seizure were not excluded from the study.

The results of Patient Reported Outcomes (PRO)-based endpoints (based on the Functional Assessment of Cancer Therapy-Prostate; FACT-P, European Organisation for Research and Treatment of Cancer quality of life; EORTC-QLQ-PR25, and EQ-5D-3L questionnaires) demonstrated maintenance of health-related quality of life (HRQoL) with a positive trend favoring darolutamide over placebo.

About the ARAMIS trial design

The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with ADT as standard of care and are at high risk for developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide twice a day or placebo along with ADT.

The primary endpoint of this trial is MFS defined as time between randomization and evidence of metastasis or death. The secondary endpoints of this trial are OS, time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first SSE, and characterization of the safety and tolerability of darolutamide.

About castration-resistant prostate cancer (CRPC)

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide. Prostate cancer is the fifth leading cause of death from cancer in men. Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system. It mainly affects men over the age of 50, and the risk increases with age. Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e. substances that stop the formation of testosterone or prevent its effect at the target location. However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.

CRPC is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly, but until recently, there have been no effective treatment options for CRPC patients who have rising Prostate-Specific Antigen (PSA) levels while on ADT and no detectable metastases. In men with progressive nmCRPC, a short PSA doubling time has been consistently associated with reduced time to first metastasis and death.

About darolutamide

Darolutamide is a non-steroidal androgen receptor antagonist with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. In addition to the Phase III trial ARAMIS in men with nmCRPC, darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS). Information about these trials can be found at www.clinicaltrials.gov.

On February 14, 2019 Gamida Cell Ltd. (Nasdaq: GMDA), a leading cellular and immune therapeutics company, reported that it will host a conference call and webcast on Thursday, February 21, 2019, at 8:00 a.m. ET to review the data from its NAM-NK and NiCord programs being presented at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of American Society for Blood and Marrow Transplantation (ASBMT) and Center for International Blood and Marrow Transplant Research (CIBMTR) (Press release, Gamida Cell, FEB 14, 2019, View Source [SID1234533329]). The meeting is taking place in Houston, Texas, February 20 – 24.

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A live webcast of the conference call can be accessed in the Investors section of Gamida Cell’s website at www.gamida-cell.com. To participate in the conference call, please dial 1-866-930-5560 (domestic) or 1-409-216-0605 (international) five minutes prior to start time. The conference ID number is 9462948. An archived version of the webcast will be available on Gamida Cell’s website for 30 days.

Details about the presentations are as follows:

Time: Wednesday, February 20, 2019, 6:45 p.m. – 7:45 p.m. CT (poster presentation)
Title: First-in-Human Phase I Study of Nicotinamide-Expanded Related Donor Natural Killer Cells for the Treatment of Relapsed/Refractory Non-Hodgkin Lymphoma and Multiple Myeloma
Poster Number: 242
Lead Author: Veronika Bachanova, M.D., Ph.D., associate professor of medicine, division of hematology, oncology and transplantation, University of Minnesota
Location: George R. Brown Convention Center, Level 3, Hall B

Time: Wednesday, February 20, 2019, 6:45 p.m. – 7:45 p.m. CT (poster presentation)
Title: Ex Vivo Nicotinamide-Expanded (NAM-Expanded) Unrelated Cord Blood Transplantation (UCB) for Refractory Severe Aplastic Anemia Results in Rapid Engraftment and Expedites Immune Recovery
Poster Number: 295
Lead Author: Joseph Clara, M.D., Hematology Branch, National Heart, Lung, and Blood Institute
Location: George R. Brown Convention Center, Level 3, Hall B

Time: Saturday, February 23, 2019, 4:45 p.m. – 5:00 p.m. CT (oral presentation)
Title: Rapid and Robust CD4+ and CD8+ T-, NK-, B-Cell, Dendritic Cell, and Monocyte Reconstitution after Nicotinamide-Expanded Cord Blood Transplantation
Abstract Number: 69
Lead Author: Jaap-Jan Boelens, M.D., Ph.D., Chief, Pediatric Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center
Location: Hilton Americas Houston, Grand Ballroom G

Abstracts are available on the 2019 TCT Meetings of ASBMT and CIBMTR website.

About NAM-NK
Gamida Cell applied the capabilities of its NAM-based cell expansion technology to highly functional NK cells to develop NAM-NK, an innate immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. NAM-NK addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. NAM-NK is in Phase 1 development through an investigator-sponsored study in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1

About NiCord
NiCord, the company’s lead clinical program, is under development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies. NiCord has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration, making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. A Phase 3 clinical study evaluating NiCord in patients with leukemia and lymphoma is ongoing in the United States, Europe and Asia.2 NiCord is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.3 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as NiCord. For more information on clinical trials of NiCord, please visit www.clinicaltrials.gov.

NAM-NK and NiCord are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On February 14, 2019 Physicians’ Education Resource (PER), a leading resource for continuing medical education (CME), reported that Tait Shanafelt, M.D., will be the keynote speaker for the 23rd annual International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas and Myeloma (Press release, Physicians’ Education Resource, FEB 14, 2019, View Source [SID1234533330]). This year’s keynote presentation will take place Saturday, March 2, from 9:15 to 9:45 a.m. at the Eden Roc Miami Beach in Florida.

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"Dr. Shanafelt brings extensive knowledge and experience in the field of physician well-being," said Phil Talamo, president of PER. "We are delighted to have him as this year’s keynote speaker for the Winter Hematology annual meeting and look forward to his discussion on ways physicians can avoid burnout and balance their lives with practicing medicine."

During his keynote presentation, "Avoiding Physician Burnout," Shanafelt will discuss strategies on how to avoid burnout and find meaning, balance and personal satisfaction in the practice of medicine. Shanafelt will also be available for a meet and greet with attendees after his keynote concludes.

Shanafelt serves as the chief wellness officer at Stanford Medicine, associate dean at the Stanford School of Medicine and director of the Stanford WellMD Center. He is an international thought leader and researcher in the field of physician well-being and its implications for quality of care. His research in this area has involved physicians at all stages of their career, from medical school to established practices, and has included several multicenter and national studies. He has numerous published works in the Journal of Clinical Oncology, Annals of Internal Medicine, and JAMA. Shanafelt has also served as a keynote speaker for the Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, American Medical Association, and American Board of Internal Medicine.

The 23rd annual congress is a three-and-a-half-day engaging and highly interactive meeting that provides community-based hematologists and medical oncologists interested in the treatment of hematologic malignancies with the opportunity to interact with internationally renowned experts in the management of leukemias, lymphomas, myeloma, myelodysplastic syndromes, myeloproliferative neoplasms and benign hematologic malignancies. During the congress, faculty experts will review latest information on pressing topics for 2019, including the expanding role of new immunologic approaches such as chimeric antigen receptor T cells and checkpoint inhibitors, the emergence of molecular-based therapies and new cytotoxic formulations in patients with acute leukemias, and new approaches for treatment and duration of therapy among patients with myeloproliferative neoplasms. The meeting will also feature several engaging Medical Crossfire discussion panels interspersed throughout the meeting to allow attendees to explore some of the most challenging clinical situations in the management of hematologic malignancies.

On February 14, 2019 Aromics, a biotech company located at the Barcelona Science Park (PCB), reported that it has been awarded with 1,085.659€ from the European Union – through the SME instrument of the Horizon 2020 (H2020-EIC-SMEInst-2018-2020-Phase 2)– for the development of the BERMES project, whose objective is the completion of the regulatory preclinics of NAX035, an innovative therapy for the treatment of malignant mesothelioma, an aggressive and highly refractory tumor directly related to asbestos exposure (Press release, Aromics, FEB 14, 2019, View Source [SID1234554043]).

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BERMES, an acronym for "A novel derivative BERberine for Malignant MESothelioma", started on first November 2018 has a duration of two and a half years and a total budget of 1.55 M €. The contribution from the European Union joins the capital of 400,000 euros already raised by the company in 2017 – with the participation of the current owners, corporative partners and also small investors that were incorporated through the crowdfunding biomedicine platform Capital Cells – and the participative loan of 120.000 € allocated by the Catalan Institute of Finance through the corporate entrepreneurship programme IFEM, which is supported by the Agency for Enterprise Competitiveness (ACC1Ó) under the program of grants in the form of a guarantee for the financing of companies participating in corporate entrepreneurship projects by means of co-investment loans (FINPEC).

Malignant mesothelioma is a tumour that emerges in the mesothelium, a thin layer of tissue that surrounds many organs such as the lung, peritoneal cavity, heart or testicles. It is an aggressive malignancy that is highly resistant to current therapies. "Patients with malignant pleural mesothelioma, the most common type, continue to have a poor prognosis, with a survival of less than 10% at five years after diagnosis. Available therapies include surgery combined with chemotherapy and radiotherapy. Most patients, however, are diagnosed in advanced stages of the disease, when chemotherapy is usually the treatment of choice. A chemotherapy with a low rate of response, despite the significant effort made over the last ten years to find a more effective treatment," explains Dr. Carmen Plasencia, the co-founder and CEO of Aromics.

El This is the focus of the BERMES project, which seeks to develop a new cure for this devastating cancer, thus meeting an important medical need.

A public health problem not yet solved

The World Health Organization (WHO) has recognized that all forms of mesothelioma are strongly associated with asbestos exposure. Although recognized as a first-level carcinogen, asbestos is still being used daily in alarming quantities in more than 150 countries according to the International Ban Asbestos Secretariat (IBAS). In fact, the WHO estimates that more than 125 million people are daily at risk of exposure, of which approximately 10% will eventually develop mesothelioma.

"Asbestos still represent a great labour, environmental and public health problem that has not been solved. Even in those countries like EU countries where it is forbidden, this material still remain in many buildings and installations. Factors such as the high costs for the safe removal of elements that contain these mineral, increase the risk of appearance of these tumours," assures Carme Plasencia.

The incidence of this cancer is increasing all over the world, being the countries of the European Union (EU) those that register the highest number of cases despite the use of asbestos was definitively prohibited on 1st January 2005 (Directive 1999/77/EC).

El Notwithstanding, the malignancy has a long latency period (a 44.6 year average from the exposure to the diagnosis) being the incidence peak expected from 2020 onwards. In fact, the European Economic and Social Committee (EESC) estimates that more than 300,000 Europeans will die of mesothelioma by 2030, at that time it is expected that the maximum number of diseases caused by exposure to asbestos will be observed.

A first-in-class drug

The NAX035 compound is one of the most advanced in the Aromics therapy portfolio. It is the first candidate molecule of a new family of antitumour agents (first-in-class) to advance up to the clinical stage.

"It is a pioneering drug, very attractive to the pharmaceutical industry. The Aromics molecule binds to a specific messenger RNA and reduces the levels of a protein that is abnormally expressed in the tumour, and that is causing resistance to current chemotherapy treatments in mesothelioma patients. In this way we aim to address the root cause, stopping the synthesis of this abnormal protein and therefore controlling the disease", says Dr. Plasencia.

The drug has already demonstrated its effectiveness in reducing the tumour size when administered both, orally or intraperitoneally in experimental animal models, showing a good toxicological and safety profile. At the same time, the biotech is working to achieve the orphan designation for NAX035, which would represent an important milestone for the company.

"This project is a clear example of the company’s activity in the area of translational medicine that leads to a better understanding of the progression of the disease and the identification of specific molecular markers relevant to the treatment response, that allow us to develop more efficient therapeutic solutions for the treatment of complex pathologies such as cancer," Dr. Plasencia says.

After completing BERMES project, Aromics’ objective is continuing with the development of the compound up to early clinical stage to prove the efficacy in patients. After the clinical proof of concept, the biotechnology foresees a licencing or co-development agreement on the product with the pharmaceutical industry that will be finally the one leading the development up to the market. Aromics is already in contact with some pharmaceutical companies that have shown interest in the drug.

On February 14, 2019 Ipsen (Euronext: IPN; ADR: IPSEY), a global specialty-driven biopharmaceutical group, reported its financial results for the full year 2018 (Press release, Ipsen, FEB 14, 2019, View Source [SID1234533314])

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Financial highlights:
▪ Group sales growth of 16.6% as reported and 20.1% at constant exchange rates1, driven by Specialty Care sales growth of 24.7%1, reflecting strong performance across all major products and geographies, and sustained growth of Consumer Healthcare at 2.7%1,2
▪ Core operating margin at 29.7% of net sales, up 3.3 points and Core Operating Income growth of 31.0%
IFRS operating margin at 23.3% of net sales, up 2.5 points and IFRS Operating Income growth of 30.8%
▪ Financial guidance for 2019 of Group sales growth greater than 13.0% at constant exchange rate and Core operating margin around 31.0% of net sales, excluding incremental investments in pipeline expansion initiatives

Q4 2018 pipeline highlights:
▪ On 15 November 2018, approval from the European Commission for Cabometyx for the treatment of hepatocellular carcinoma (HCC) in adults who have previously been treated with sorafenib
▪ On 5 December 2018, initiation with Exelixis of COSMIC-312, a Phase 3 pivotal trial of Cabometyx in combination with atezolizumab versus sorafenib in previously untreated advanced hepatocellular carcinoma (HCC)

David Meek, Chief Executive Officer of Ipsen, stated: "2018 was a tremendous year for Ipsen with industry-leading top-line growth and Somatuline achieving blockbuster status. We also delivered significant margin expansion while investing to advance our R&D pipeline. The momentum of the business is strong as we enter 2019 and are on track to deliver our 2020 financial targets to exceed €2.5 billion in sales and 30% margins, one year earlier.
In 2018, we advanced our pipeline with Cabometyx approvals in additional indications, acceleration of key programs and the establishment of new collaborations. We remain focused on executing our internal and external innovation strategy to build a robust pipeline, ensure continued growth and optimize value for patients and shareholders. We look forward to another outstanding year of strong industry-leading growth, expanding indications for our current medicines and advancing several innovative new chemical entities in the clinic."

Review of full year 2018 results

Note: Unless stated otherwise, all variations in sales are calculated excluding foreign exchange impacts established by recalculating net sales for the relevant period at the rate used for the previous period.

Group net sales reached €2,224.8 million, up 20.1% year-on-year.

Specialty Care sales reached €1,924.5 million, up 24.7%, driven by the strong growth of Somatuline and the €257.6 million contribution from the key Oncology launches of Cabometyx and Onivyde. Somatuline growth of 24.4% was driven by continued positive momentum in North America (38.2% growth in the U.S.) and solid performance throughout Europe. Dysport growth was fueled by strong performance and the resupply in Brazil, strong volume growth in the U.S. in the therapeutics market as well as the good performance of Galderma in the aesthetics market in Europe. Decapeptyl sales reflect good volume growth across Europe and a good performance in China.

Consumer Healthcare sales reached €300.3 million, up 2.7% year-on-year re-stated from Etiasa new contractual set-up (or down 2.9% as reported), driven by the good performance of Smecta and the contribution of the products acquired in 2017.

Core Operating Income reached €659.9 million in 2018, compared to €503.6 million in 2017, a growth of 31.0%, driven by the sales growth and after increased commercial investments for Cabometyx and Onivyde, and R&D investments to support the development of the growing pipeline.

Core operating margin reached 29.7% of net sales, up 3.3 points compared to 2017.

Core consolidated net profit was €491.6 million in 2018, an increase of 35.5% versus €362.7 million in 2017, driven by higher Core Operating Income and due to lower effective tax rate and net financing costs.

Fully diluted Core earnings per share grew by 35.5% to reach €5.91, compared to €4.36 in 2017.

IFRS Operating income was €519.4 million, up 30.8% after higher amortization of intangible assets (excluding software) and impairment charges. Operating margin of 23.3% was up 2.5 points compared to 2017.

IFRS Consolidated net profit was €389.1 million versus €272.9 million in 2017, up 42.6%.

IFRS Fully diluted EPS (Earning per share) was €4.68 versus €3.28 in 2017.

Free Cash Flow reached €458.4 million, up by €149.4 million or 48.3%, mainly driven by an improvement in Operating Cash Flow and lower restructuring costs, partially compensated by higher financial income and current income tax.

Closing net debt reached €242.5 million at the end of 2018, an improvement of €220.8 million over the closing net debt in 2017 of €463.3 million. This reflects positive Free Cash Flow generation of the Group which allowed the payment of milestones for Cabometyx and dividends in June.

Comparison of 2018 performance with financial objectives

The Group exceeded its upgraded guidance provided on 26 July 2018 for Group sales growth and for Core operating margin.

The table below shows the comparison between the financial objectives provided on 26 July 2018 and 2018 actuals.

Dividend for the 2018 financial year proposed for the approval of Ipsen’s shareholders

The Ipsen S.A. Board of Directors, which met on 13 February 2019, decided to propose at the Annual Shareholders’ meeting on 28 May 2019 the payment of a dividend of €1.00 per share for the 2018 financial year, unchanged from the prior year.

2019 Financial guidance

The Group has set the following financial targets for 2019:

Group sales growth year-on-year at constant currency greater than +13.0%; based on the current level of exchange rates, sales growth at current rates would be positively impacted by around 1.0%.
Core operating margin around 31.0% of net sales, excluding incremental investments in pipeline expansion initiatives.

Conference call

Ipsen will hold a conference call Thursday, 14 February 2019 at 2:30 p.m. (Paris time, GMT+1). Participants should dial in to the call approximately five to ten minutes prior to its start. No reservation is required to participate in the conference call.

Standard International: +44 (0) 2071 928000

France and continental Europe: +33 (0) 1 76 70 07 94

UK: 08-445-718-892

U.S.: 1-6315-107-495

Conference ID: 2989606