On September 5, 2022 AstraZeneca reported it’s Imfinzi (durvalumab) has been approved in the US for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin) (Press release, AstraZeneca, SEP 5, 2022, View Source [SID1234618994]).

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The approval by the Food and Drug Administration (FDA) was based on the results from the TOPAZ-1 Phase III trial. In an interim analysis of TOPAZ-1, Imfinzi plus chemotherapy reduced the risk of death by 20% versus chemotherapy alone (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). An estimated one in four (25%) patients treated with Imfinzi plus chemotherapy were still alive at two years compared to one in 10 (10%) treated with chemotherapy alone. Results were consistent across all prespecified subgroups, regardless of PD-L1 expression or tumour location.

BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder.1,2 Approximately 23,000 people in the US are diagnosed with BTC each year.1 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.3

Aiwu Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, and a lead investigator in the TOPAZ-1 Phase III trial, said: "This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated and effective treatment options after more than a decade of limited innovation. The combination of durvalumab and chemotherapy should become a new standard of care in this setting, having demonstrated significantly improved survival for these patients who have historically faced a poor prognosis."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "For the first time, patients in the US with advanced biliary tract cancer have an immunotherapy-based treatment option that meaningfully extends survival and is well-tolerated. This approval for Imfinzi and chemotherapy advances our ambition to challenge treatment expectations and transform care for patients with gastrointestinal cancers with high unmet need."

Stacie Lindsey, CEO, Cholangiocarcinoma Foundation, said: "Patients have been waiting a long time for a new, first-line treatment option for biliary tract cancer. The Foundation congratulates AstraZeneca for engaging in rare cancer research, which impacts patients and families nationwide. We are especially grateful to the patients who participated in this trial making it possible for the broader rare disease community to benefit from this treatment."

The TOPAZ-1 Phase III trial results were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) Symposium and published in the New England Journal of Medicine Evidence. Imfinzi plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.

In July 2022, Imfinzi plus chemotherapy was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a Category 1 preferred regimen as 1st-line therapy for locally advanced or metastatic BTC based on the data from TOPAZ-1.4

The US regulatory submission for TOPAZ-1 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Imfinzi plus chemotherapy is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration, Singapore’s Health Sciences Authority, Switzerland’s Swissmedic and the UK’s Medicines and Healthcare products Regulatory Agency.

The approval was granted after securing Priority Review and Orphan Drug Designation for Imfinzi in the US in this setting. Regulatory applications are also currently under review in Europe, Japan and several other countries based on the TOPAZ-1 results.

Notes

Biliary tract cancer
BTC is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).1,2

Cholangiocarcinoma is more common in China and South-East Asia and is on the rise in Western countries.1,3 Gallbladder cancer is more common in certain regions of South America, India and Japan.5

Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.3,5,6

TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to the approval in BTC, Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy and is the global standard of care in this setting based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.

Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer, and other solid tumours.

Imfinzi combinations have demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).

AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.6

Within this programme, the Company is committed to improving outcomes in gastric, liver, BTC, oesophageal, pancreatic, and colorectal cancers.

Imfinzi is being assessed in combinations in liver, BTC, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease.

The Company aims to understand the potential of Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, in the two most common GI cancers, colorectal and gastric cancers. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome evasion of the anti-tumour immune response. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient.

In addition, the ability to combine the IO portfolio with radiation, chemotherapy, and targeted small molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On September 5, 2022 Center for Translational Research CTR reported that it is a group of complementary life science service companies providing expert services and advice within product development (Press release, Symeres, SEP 5, 2022, View Source [SID1234618992]). The services provided by Admescope Sweden/Metasafe complements well the current offerings and will contribute to a more seamless development process bringing value for our customers.

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Metabolites in safety testing (MIST studies) is a natural component of the early clinical development program and thereby fits very well with the services provided by the CTR-group. By this transfer, the expansion of CTR continues to build on combining key competencies and technologies with the capability to cover projects from pre-clinical to market approval.

The collaboration between the CTR-group and Admescope and Symeres will further strengthen the access to key competences and techniques in pre-clinical development.

The activities will continue without interruption and with the same staff, in the same facilities, using the same instrumentation. Johanna Haglund, Business Development Scientist and Head of Safety Metabolism, will lead the team.

Karin Meyer, CEO at CTR says: "Through the transfer of Admescope Sweden/Metasafe to our group we will be able to offer a more integrated approach and develop the services for our customers using the talented staff and facilities in the human metabolite profiling and characterisation area. We look forward to the collaboration with Admescope and Symeres, aiming for a more complete solution for several projects."

Outi Kontkanen, CEO Admescope says: "Admescope, as part of Symeres, continues to focus on delivering tailored solutions in non-clinical ADME support and toxicology, with strategic investments to further expand our services in these areas globally. We look forward to continued collaborations with the CTR group and are pleased that our talented MIST-team has a new home where it fits to the clinical drug development landscape."

Symeres CEO Eelco Ebbers comments: "With this transfer we will have a very logical consolidation of our ADME services at two sites, namely Nijmegen in the Netherlands and Oulu in Finland which allows us to focus our development investments. Symeres looks forward to further collaboration with CTR which will strengthen our access to key competences and techniques in pre-clinical development."

On September 5, 2022 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported a poster presentation titled: High Activity of Poziotinib in G778_P780dup HER2 Exon 20 Insertion Mutations in Non-Small Lung Cancer (NSCLC) (Press release, Spectrum Pharmaceuticals, SEP 5, 2022, View Source [SID1234618991]). The poster will be presented at the upcoming European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) 2022 that will take place in Paris from September 9-13, 2022.

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Details of the ESMO (Free ESMO Whitepaper) poster presentation are as follows:

Title: High Activity of Poziotinib in G778_P780dup HER2 Exon 20 Insertion Mutations in Non-Small Lung Cancer (NSCLC)
First Author: Xiuning Le, M.D., Ph.D., Assistant Professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston
Location: Hall 4
Date: Monday, September 12, 2022
Presentation Number: 1172P

The poster will be available for viewing by registered participants during the conference via the ESMO (Free ESMO Whitepaper) website on September 10, 2022. It will also be available on the Investor Relations section of the company’s website at View Source

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. HER2 exon 20 insertion mutations are a rare subset accounting for approximately 2-4% in NSCLC. There is no approved therapy specifically for either treatment-naïve or previously treated NSCLC with HER2 exon 20 insertion mutations. The company holds an exclusive license from Hanmi Pharmaceutical to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China.

On September 5, 2022 CVS Health (NYSE:CVS) and Signify Health (NYSE: SGFY) ("Signify") reported that they have entered into a definitive agreement under which CVS Health will acquire Signify Health for $30.50 per share in cash, representing a total transaction value of approximately $8 billion (Press release, Signify Health, SEP 5, 2022, View Source [SID1234618990]).

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Signify Health is a leader in Health Risk Assessments, value-based care and provider enablement. With a network of more than 10,000 clinicians across all 50 states and a nationwide value-based provider network, combined with its proprietary analytics and technology platforms, Signify Health is improving patient engagement, patient outcomes and care coordination for stakeholders across the health care system. Signify Health’s clinicians and providers can have an even greater impact by engaging with CVS Health’s unique collection of assets and connecting patients to care how and when they need it.

"Signify Health will play a critical role in advancing our health care services strategy and gives us a platform to accelerate our growth in value-based care," said CVS Health President and CEO, Karen S. Lynch. "This acquisition will enhance our connection to consumers in the home and enables providers to better address patient needs as we execute our vision to redefine the health care experience. In addition, this combination will strengthen our ability to expand and develop new product offerings in a multi-payor approach."

Signify Health’s network of clinicians – physicians, nurse practitioners and physician assistants – utilize home-based visits to identify a patient’s clinical and social needs, and then connect them to appropriate follow-up care and community-based resources in order for the patient to have a more connected, effective care experience. In 2022, Signify Health’s clinicians expect to connect with nearly 2.5 million unique members in the home, both in-person and virtually, and on average they spend 2.5 times longer with a patient in the home than providers spend in the average primary care office visit.

Notably, since acquiring Caravan Health in March 2022, Signify Health has further expanded its focus on value-based care and population health. Today, Caravan is already a partner to over 170 providers participating in accountable care organizations (ACOs) serving Medicare beneficiaries with a focus on improving the health of underserved communities. Signify Health recently announced that its ACOs generated more than $138 million in gross savings in 2021, and in 2023 the Caravan business is expected to serve ACOs representing over 700,000 people – rivaling many standalone platforms. As part of CVS Health, Signify Health will continue to advance its extensive primary care enablement capabilities, including turnkey analytics, network, and practice improvement solutions, to help providers transition to value-based reimbursement and improve quality of care.

"Signify Health’s mission is to build trusted relationships to make people healthier by using actionable intelligence to understand what’s really impacting outcomes and cost today," said Kyle Armbrester, CEO of Signify Health. "As we carefully considered our long-term strategic options, we determined that CVS Health is the ideal partner, given its focus on expanding access to health services and helping consumers navigate to the best sites of care. We are both building an integrated experience that supports a more proactive, preventive and holistic approach to patient care, and I look forward to executing on our shared vision for the future of care delivery."

"We formed Signify Health and recruited Kyle and the team to build a strategic innovation platform focused on leveraging technology as a catalyst for connecting key health care stakeholders to drive better patient outcomes," said Matt Holt, Chairman of the Board, Signify Health and President of Private Equity and Managing Director at New Mountain Capital, which owns a majority stake in Signify Health. "Together with CVS Health, Signify is uniquely positioned to continue to lead the transformation to value-based care. We look forward to the significant impact this transaction will make on health care for years to come."

Following the close of the transaction, Kyle Armbrester will continue to lead Signify Health as part of CVS Health. Signify Health’s extensive network of over 50 health plan clients and their members will further augment CVS Health’s longstanding and leading offering of payor-agnostic solutions for a diverse set of health plan and employer clients.

Transaction details

CVS Health will acquire Signify Health’s stock for $30.50 per share. CVS Health expects to fund the transaction with existing cash from its balance sheet and available resources and is committed to maintaining its current credit ratings. The transaction was approved by the Board of Directors at each of the respective companies. It is subject to approval by a majority of Signify Health’s stockholders, receipt of regulatory approval and satisfaction of other customary closing conditions. Private equity funds affiliated with New Mountain Capital, which owns approximately 60% of the common stock of Signify Health, have agreed to vote the shares they own in favor of the transaction, subject to customary exceptions. CVS Health and Signify Health anticipate that the transaction will close in the first half of 2023.

"This is a major step as we continue to execute on our strategy," said CVS Health Executive Vice President and Chief Financial Officer Shawn Guertin. "We expect the acquisition to be meaningfully accretive to earnings and, as a result, are increasingly confident we can achieve our long-term adjusted EPS goals as outlined at our Investor Day in December 2021."

Joint Conference Call and Webcast

CVS Health and Signify Health will hold a joint conference call for analysts and investors on September 6, 2022 at 8:30 a.m. ET. An audio webcast of the conference call will be broadcast simultaneously on the Investor Relations portion of the CVS Health website at investors.cvshealth.com where it will be archived for a period of one year.

Advisors

BofA Securities is serving as financial advisor to CVS Health. CVS Health was advised on legal matters by Fried, Frank, Harris, Shriver & Jacobson LLP, Dechert LLP, and McDermott Will & Emery LLP. Goldman Sachs & Co. LLC and Deutsche Bank Securities Inc. are serving as financial advisors to Signify Health. Ropes & Gray LLP is acting as Signify Health’s legal advisor.

On September 5, 2022 Phynova Group Ltd reported a new strategic partnership with Singapore-based Nutraconnect Pte, Ltd. to introduce its innovative, scientifically backed nutraceutical ingredient Reducose to critical markets in Asia namely Indonesia & Thailand (Press release, Phynova, SEP 5, 2022, View Source [SID1234618989]). This strategic partnership will also aim to take Reducose to certain Key marquee brands in the APAC region. Reducose turns fast sugars and other carbohydrates into slow ones. It empowers consumers to take back control of their blood sugar fluctuations in response to foods. Reducose is a patented functional ingredient, that is a water extract of white mulberry leaves. It can easily be incorporated into a wide range of foods and drinks or be used in dietary supplements. In several human clinical trials, Reducose has been studied to lower blood glucose after eating foods containing sugars and other carbohydrates. Reducose has also been shown to lower the amount of insulin our bodies need to make, and Reducose will decrease the Glycaemic Index (GI) of common carbohydrates. Blood sugar management is a major health benefit of concern for healthy people who actively seek to manage their energy, concentration, weight and lifestyle. Blood sugar management is also critical for people who live with diabetes or pre-diabetes. Diabetes is now a disease of major concern both globally and in APAC and is a leading cause of death in most countries. In 2021, the International Diabetes Federation (IDF) estimated that ∼537 million people had diabetes worldwide, and by 2030, this is predicted to rise to 643 million. Eighty percent live in low-and middle-income countries, and of the total, more than 60% live in Asia, with almost one-third in China. This strategic partnership combines the strengths of the two companies to bring a natural solution to the consumers who actively seek to live a healthier life through better control of their blood sugar. Stephane Ducroux, CEO at Phynova, said: "We are delighted to have a Strategic Partnership with Nutraconnect. Phynova’s strategy is to partner with market focused experts such as Nutraconnect who have a proven track record of introducing and developing opportunities for ingredients with a strong science like Reducose to certain key marquee brands in the APAC region. "The aim of Nutraconnect is to bring innovative, safe and science backed natural solutions to brand customers in the APAC region. We guide our clients through the regulatory, language, cultural and distribution labyrinth using our experience, reach and knowledge so that we can successfully bring products like Reducose to the market. We are proud of our association with Phynova Group Limited" adds Nikhil Sawant, CEO and Co-founder of Nutraconnect. "To develop formulations that comply to the local regulations, brand customers expect great service and rapid responses, Nutraconnect is based in Asia and in the same time zone as its customers enabling us to meet and exceed the expectations of our customers. The services provided by Nutraconnect is an added competitive advantage for our client to win in the APAC region" adds Rohit Noronha, Chief Growth Officer, and Co-founder of Nutraconnect.

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