On July 27, 2017 AstraZeneca reported that the Phase III FLAURA trial showed a statistically-significant and clinically-meaningful progression-free survival (PFS) benefit with Tagrisso (osimertinib) compared to current 1st-line standard-of-care treatment (erlotinib or gefitinib) in previously-untreated patients with locally-advanced or metastatic epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUL 27, 2017, View Source [SID1234519898]). Schedule your 30 min Free 1stOncology Demo! Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The strong results from the FLAURA trial are very exciting news for patients with EGFR mutation-positive non-small cell lung cancer, providing physicians with a potential new first-line treatment option to improve outcomes in this disease. We will now initiate discussions with global health authorities on the data and regulatory submissions."
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The efficacy, safety and tolerability profiles for Tagrisso, erlotinib and gefitinib were consistent with current knowledge. A full evaluation of the FLAURA data is ongoing. Further results will be presented at a forthcoming medical meeting.
About NSCLC
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-quarter of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with currently-available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to EGFR-TKI treatment leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib and erlotinib due to the resistance mutation, EGFR T790M. Tagrisso targets this secondary mutation that leads to disease progression. There is also a need for agents with improved CNS efficacy since approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.
About Tagrisso
Tagrisso is a third generation, irreversible EGFR tyrosine kinase inhibitor (TKI) designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations, with clinical activity against central nervous system (CNS) metastases. Tagrisso (osimertinib) 40mg and 80mg once-daily oral tablets have been approved in more than 50 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.
About FLAURA
FLAURA assessed the efficacy and safety of Tagrisso 80mg once-daily treatment versus standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously untreated patients with locally advanced or metastatic EGFR mutation-positive NSCLC. The trial was a double-blinded, randomised study, with 556 patients across 30 countries.
The primary endpoint of the trial was PFS, and secondary endpoints included overall survival, objective response rate, duration of response, disease control rate, safety and measures of health-related quality of life (HRQoL).
About AstraZeneca in Lung Cancer
AstraZeneca is using ground-breaking science to develop a wide range of medicines for patients with lung cancer. We are pioneering precision medicines that target molecular mutations in tumour cells, as well as those that aim to boost the power of the immune response against cancer. We are committed to transforming outcomes for patients with lung cancer, whose treatment options are currently limited.
AstraZeneca and Merck establish strategic oncology collaboration
OnJuly 27, 2017 AstraZeneca and Merck & Co., Inc., (Merck; known as MSD outside of the US and Canada) reported that they have entered a global strategic oncology collaboration to co-develop and co-commercialise AstraZeneca’s Lynparza (olaparib) for multiple cancer types. Lynparza is an innovative, first-in-class oral poly ADP ribose polymerase (PARP) inhibitor currently approved for BRCA-mutated ovarian cancer in multiple lines of treatment (Press release, AstraZeneca, JUL 27, 2017, View Source [SID1234519892]). Schedule your 30 min Free 1stOncology Demo! Lynparza’s pipeline has grown significantly in the last few years, with 14 indications currently being developed across several tumour types, including breast, prostate and pancreatic cancers. The strategic collaboration is expected to further increase the number of treatment options available to patients.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The companies will develop and commercialise Lynparza jointly, both as monotherapy and in combination with other potential medicines. Independently, the companies will develop and commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab).
The companies will also jointly develop and commercialise AstraZeneca’s selumetinib, an oral, potent, selective inhibitor of MEK, part of the mitogen-activated protein kinase (MAPK) pathway, currently being developed for multiple indications including thyroid cancer.
Pascal Soriot, Chief Executive Officer of AstraZeneca, said: "Our strategic collaboration builds on scientific evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumours. By bringing together the expertise of two leading oncology innovators, we will accelerate Lynparza’s potential to become the preferred backbone of many immuno-oncology combination therapies as the world’s first and leading PARP inhibitor. This is a truly exciting step and we are pleased to work with Merck, a company that shares our passion for science to deliver new medicines for cancer patients."
Kenneth C. Frazier, Chief Executive Officer of Merck, said: "This global collaboration between AstraZeneca and Merck, two oncology leaders, will increase the possibilities for patients to have more treatment options for more cancers. Merck continues to build its leadership in immuno-oncology with Keytruda as foundational in monotherapy and combination therapy, and this collaboration expands our oncology leadership into the growing targeted therapies of PARP and MEK inhibitors. We look forward to working with AstraZeneca to create greater value for patients and shareholders than if both companies worked independently."
Financial considerations
Under the terms of the agreement, AstraZeneca and Merck will share the development and commercialisation costs for Lynparza and selumetinib monotherapy and non-PD-L1/PD-1 combination therapy opportunities. Gross profits from Lynparza and selumetinib Product Sales generated through monotherapies or combination therapies will be shared equally.
Merck will fund all development and commercialisation costs of Keytruda in combination with Lynparza or selumetinib. AstraZeneca will fund all development and commercialisation costs of Imfinzi in combination with Lynparza or selumetinib.
AstraZeneca will continue to manufacture Lynparza and selumetinib.
As part of the agreement, Merck will pay AstraZeneca up to $8.5 billion in total consideration, including $1.6 billion upfront, $750 million for certain license options and up to $6.15 billion contingent upon successful achievement of future regulatory and sales milestones. Under the terms of the agreement, AstraZeneca anticipates approximately $1 billion to be recorded under Externalisation Revenue in 2017.
AstraZeneca will book all Product Sales of Lynparza and selumetinib; gross profits due to Merck under the collaboration will be recorded under Cost of Sales. The initial, regulatory and commercial milestone payments will be recorded under Externalisation Revenue. The transaction does not impact AstraZeneca’s 2017 financial guidance. AstraZeneca continues to anticipate that the sum of Externalisation Revenue and Other Operating Income in FY 2017 will be ahead of that in FY 2016.
The collaboration agreement was completed upon signing on 26 July 2017.
For the purposes of the UK Listing Authority’s Listing Rule LR 10.4.1 R (Notification of class 2 transactions), the book value of gross assets subject to the license and collaboration is approximately $242 million. In view of the development and early growth phase of the medicines, a pre-tax loss of $231 million was attributable to Lynparza and selumetinib in aggregate in the year to 31 December 2016.
NOTES TO EDITORS
About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DDR pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines that target DDR mechanisms in cancer cells. Lynparza is currently 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. It is also approved in the US as a monotherapy for patients with deleterious, or suspected deleterious, germline BRCA-mutated (as detected by a US FDA test) advanced ovarian cancer, who have been treated with three or more lines of chemotherapy.
The Company recently presented positive results for Lynparza from its Phase III OlympiAD trial that showed a statistically-significant and clinically-meaningful improvement in progression-free survival for patients treated with Lynparza tablets (300mg twice daily), compared to treatment with physician’s choice of a standard of care chemotherapy. OlympiAD, a randomised, open label, multi-centre Phase III trial assessing the efficacy and safety of Lynparza in patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are predicted or suspected to be deleterious, was the first positive Phase III trial to evaluate the efficacy and safety of PARP inhibitor beyond ovarian cancer. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III trial called OLYMPIA. This trial is still open and recruiting patients internationally.
Lynparza generated Product Sales in 2016 of $218 million.
About selumetinib
Selumetinib, licensed by AstraZeneca from Array BioPharma Inc. in 2003, inhibits the MEK enzyme in the RAS/RAF/MEK/ERK pathway in cancer cells to prevent the tumour from growing. Selumetinib is in Phase III development for differentiated thyroid cancer, for which it was granted Orphan Drug Designation by the FDA in May 2016.
Selumetinib is also being tested in a separate Phase II trial in patients with paediatric neurofibromatosis type-1, and in a Phase I trial with patients suffering from advanced solid tumours.
About AstraZeneca in Oncology
AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer
On July 27, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported progression-free survival (PFS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy or Imfinzi in combination with tremelimumab versus platinum-based standard-of-care (SoC) chemotherapy in previously-untreated patients with metastatic (Stage IV) 1st-line non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUL 27, 2017, View Source [SID1234519897]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving PFS compared to SoC in patients whose tumours express PD-L1 on 25% or more of their cancer cells (as determined by the VENTANA PD-L1 (SP263) assay).
As a secondary endpoint, although not formally tested, Imfinzi monotherapy would not have met a pre-specified threshold of PFS benefit over SoC in this disease setting.
The trial will continue to assess two additional primary endpoints of overall survival (OS) for Imfinzi monotherapy and OS for the Imfinzi plus tremelimumab combination. Final OS data from both primary endpoints are expected during the first half of 2018.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "While the results from the MYSTIC trial for progression-free survival in first-line Stage IV non-small cell lung cancer compared with standard of care are disappointing, the trial was designed to assess overall survival and we look forward to evaluating the remaining primary endpoints of overall survival for both mono- and combination therapy."
AstraZeneca recently received accelerated approval from the US FDA for Imfinzi in previously-treated patients with locally advanced or metastatic urothelial carcinoma (mUC).
About MYSTIC
The MYSTIC trial is a randomised, open-label, multi-centre, global Phase III trial of Imfinzi monotherapy or Imfinzi in combination with tremelimumab versus SoC in treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally-advanced or metastatic (Stage IV) 1st-line NSCLC. Lung cancer is an unapproved use of Imfinzi.
The trial is being conducted in 167 centres across 17 countries, including the US, Canada, Europe, parts of Asia including Japan, Korea, Thailand, Taiwan and Vietnam, and in Russia and Australia. Primary endpoints include PFS and OS.
About Imfinzi
Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response.
Imfinzi continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in immuno-oncology. Imfinzi is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in mUC and in head and neck squamous cell carcinoma (HNSCC). The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in mUC, NSCLC, SCLC and HNSCC and in Phase I/II trials in hepatocellular carcinoma (HCC) and haematological malignancies.
About Tremelimumab
Tremelimumab is an investigational human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Tremelimumab is being investigated in an extensive clinical trial programme in combination with Imfinzi, in NSCLC, mUC, HNSCC, HCC and blood cancers.
About AstraZeneca in NSCLC
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined.
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of NSCLC across all stages of disease and lines of therapy. We aim to address unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa and Tagrisso and ongoing FLAURA and ADAURA trials. Our extensive late-stage immuno-oncology programme focuses on 75-80% of patients with NSCLC without a known genetic mutation. Our portfolio includes Imfinzi (durvalumab), an anti-PDL1 antibody, which is in development as monotherapy (ADJUVANT, PACIFIC, MYSTIC, PEARL and ARCTIC trials) and in combination with tremelimumab, an anti-CTLA-4 (MYSTIC, NEPTUNE and POSEIDON trials).
Eisai Submits Simultaneous Applications in The United States and Europe for Lenvatinib in Hepatocellular Carcinoma
On June 26, 2017 Eisai Co., Ltd. reported that it has submitted applications to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for its in-house discovered and developed anticancer agent lenvatinib mesylate (lenvatinib) for the treatment of hepatocellular carcinoma (HCC) (Press release, Eisai, JUL 26, 2017, View Source [SID1234528955]). This follows the application in Japan. Lenvatinib for the treatment of HCC is designated as an orphan drug by the FDA.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
This application is based on the results of the REFLECT study (Study 304), a multicenter, open-label, randomized, global Phase III trial comparing the efficacy and safety of lenvatinib versus sorafenib, a standard treatment for HCC, as a first-line treatment for 954 patients with unresectable HCC.(1)
In the REFLECT study, lenvatinib met the primary endpoint and demonstrated an overall survival (OS) treatment effect by the statistical confirmation of non-inferiority compared to sorafenib. Developing first-line treatments for HCC is challenging, and over the past 10 years, four previous first-line Phase III studies investigating other agents compared to sorafenib have failed to achieve this endpoint in OS.(2)
Additionally, lenvatinib showed highly statistically significant and clinically meaningful improvements in the secondary endpoints of Progression Free Survival (PFS), Time To Progression (TTP), and Objective Response Rate (ORR). In this study, the five most common adverse events observed in the lenvatinib arm were hypertension, diarrhea, decreased appetite, weight loss and fatigue, which is consistent with the known side-effect profile of lenvatinib.
Liver cancer is the second leading cause of cancer related death and is estimated to be responsible for 750,000 deaths per year globally (27,000 per year in the US, 62,000 per year in Europe), with 780,000 cases newly diagnosed each year (30,000 per year in the US, 63,000 per year in Europe).(3) HCC accounts for 85 percent to 90 percent of liver cancer cases. Treatment options for unresectable HCC are limited and the prognosis is very poor, making this an area of high unmet medical need.
Lenvatinib is approved as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, and in Europe, under the brand name Lenvima. Additionally, lenvatinib in combination with everolimus is approved for the treatment of renal cell carcinoma (RCC) in over 35 countries, including the United States and in Europe. In Europe, lenvatinib was launched under the brand name Kisplyx for RCC.
Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Eisai is committed to exploring the potential clinical benefits of lenvatinib as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to patients with cancer, their families, and healthcare providers.
About lenvatinib mesylate (generic name, "lenvatinib", product name: Lenvima/ Kisplyx)
Discovered and developed in-house, lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and RET) involved in tumor proliferation. Currently, Eisai has obtained approval for lenvatinib as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, and in Europe, under the brand name Lenvima. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 35 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for RCC. A Phase III study of lenvatinib in separate combinations with everolimus and pembrolizumab in renal cell carcinoma (first-line) was initiated and is underway. A Phase Ib/II study to investigate the agent in combination with pembrolizumab in select solid tumors (non-small cell lung cancer, renal cell carcinoma, endometrial cancer, urothelial cancer, head and neck cancer, and melanoma) and a Phase Ib study in HCC are also underway. Following the submission of applications in Japan (June 2017), the United States and Europe (July 2017), Eisai also plans to submit an application for lenvatinib for the treatment of HCC in China within the latter half of fiscal 2017.
About the RELECT study (Study 304)(1)
The REFLECT study (A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable HCC) is a multicenter, open-label, randomized, global Phase III study comparing the efficacy and safety of lenvatinib versus sorafenib. In the study, 954 patients were randomized in a 1:1 ratio to receive lenvatinib 12 mg (=/>60 kg) or 8 mg (<60 kg) once a day, depending on baseline body weight (n= 478) or sorafenib 400 mg twice a day (n= 476). Treatment was continued until disease progression or unacceptable toxicity.
Oncolytics Biotech® to Present REOLYSIN® Safety Data in combination with chemotherapy at ESMO 2017 Congress
On July 26, 2017 Oncolytics Biotech Inc. (Oncolytics or the Company) (TSX:ONC) (OTCQX:ONCYF) reported that two abstracts describing both pooled safety and tolerability data and the mechanism of REOLYSIN, also known as pelareorep, have been selected for poster presentation (display) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress (Press release, Oncolytics Biotech, JUL 26, 2017, View Source [SID1234519895]). The abstracts will be published online on the ESMO (Free ESMO Whitepaper) website at 3:05 ET on Wednesday, August 30. The conference is taking place from September 8-12, 2017, in Madrid, Spain.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The pooled analysis of patients treated with intravenous pelareorep is the largest safety database available for this class of agents in combination with chemotherapy," said Dr. Andres Gutierrez, Chief Medical Officer at Oncolytics Biotech. "While our efficacy in metastatic breast cancer announced earlier this year at AACR (Free AACR Whitepaper) was captivating, the safety component of pelareorep increases the benefit-risk ratio of the therapy and supports its further development. We are particularly excited to present these results as other immuno-oncology agents in the same class have had limited or no experience with systemic administration."
Publication number: 1193P
Title: Pooled data analysis of the safety and tolerability of intravenous Pelareorep in combination with chemotherapy in 500 + cancer patients
Lead Author: Dr. Andres Gutierrez, Oncolytics Biotech
Publication number: 523P
Title: Mechanism of Pelareorep (Pel)-mediated cell death in a Phase I study in combination with irinotecan/ fluorouracil/ leucovorin/ bevacizumab (FOLFIRI/B) in patients with KRAS mutant metastatic colorectal cancer (mCRC)
Lead Author: Dr. Sanjay Goel, Montefiore Medical Center, NY
The Company also announced that it has been granted an End-of-Phase 2 meeting with the United States Food and Drug Administration (FDA), taking place in August 2017. The meeting will address registration pathways for REOLYSIN for the treatment of metastatic breast cancer, the indication for which the FDA has granted Fast Track designation. The Company expects to announce the outcome of this meeting in the fourth quarter of 2017.