On April 14, 2021 AstraZeneca reported that Tagrisso (osimertinib) has been approved in China for the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumour resection with curative intent, with or without adjuvant chemotherapy as recommended by the patient’s physician (Press release, AstraZeneca, APR 14, 2021, View Source [SID1234578011]). Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

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The approval by China’s National Medical Products Administration (NMPA) was based on positive results from the ADAURA Phase III trial. In the trial, Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC. The ADAURA trial also showed a statistically significant and clinically meaningful improvement in DFS in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.

While up to 30% of all patients with NSCLC may be diagnosed early enough to have surgery with curative intent, recurrence is still common in early-stage disease. Historically, nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, have experienced recurrence within five years.1-3 More than a third of the world’s lung cancer patients are in China and among those with NSCLC, approximately 40% have tumours with an EGFR mutation.4-6

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "The expedited approval of Tagrisso in China as part of a curative-intent regimen for early-stage EGFR-mutated lung cancer underscores the high unmet need in this setting and our commitment to improving outcomes in a country with one of the highest rates of EGFR mutations in the world. This approval reinforces the importance of EGFR testing across all stages of lung cancer, prior to treatment decisions, to ensure as many patients as possible can benefit from targeted therapies like Tagrisso and live cancer-free longer."

In the ADAURA trial, adjuvant treatment with Tagrisso reduced the risk of disease recurrence or death by 83% in patients with Stage II and IIIA disease (hazard ratio [HR] 0.17; 99.06% confidence interval [CI] 0.11-0.26; p<0.001) and by 80% in the overall trial population of patients with Stage IB-IIIA disease (HR 0.20; 99.12% CI 0.14-0.30; p<0.001).

Consistent DFS results were seen regardless of prior adjuvant chemotherapy use and across all prespecified subgroups, including in Asian and non-Asian patients. The safety and tolerability of Tagrisso in this trial was consistent with previous trials in the metastatic setting. The ADAURA results were published in The New England Journal of Medicine.

Tagrisso is approved to treat early-stage lung cancer in more than a dozen countries, including the US, and additional global regulatory reviews are ongoing. Tagrisso is also approved for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in China, and in the US, Japan, the EU and many other countries.

This approval follows a priority review designation by the NMPA’s Center for Drug Evaluation. It marks the third approved indication for Tagrisso in China following previous approvals in 2nd-line T790M and 1st-line EGFRm NSCLC, which are both included on the National Reimbursement Drug List.

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.4 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.7 The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-2 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.8-9

For patients with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.3

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.10-12 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.13

ADAURA
ADAURA is a randomised, double-blind, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II and IIIA EGFRm NSCLC following complete tumour resection and adjuvant chemotherapy as indicated. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial enrolled patients in more than 200 centres across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients.

The data readout was originally anticipated in 2022. In April 2020, an Independent Data Monitoring Committee recommended for the trial to be unblinded two years early based on a determination of overwhelming efficacy. Investigators and patients continue to participate and remain blinded to treatment. The trial will continue to assess overall survival.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat approximately 250,000 patients across indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

In Phase III trials, Tagrisso is being tested in the Stage III locally advanced unresectable setting (LAURA), in the neoadjuvant resectable setting (NeoADAURA) and in combination with chemotherapy (FLAURA2). AstraZeneca is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, which test Tagrisso given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, stages of disease, lines of therapy and modes of action. These medicines include Tagrisso, Imfinzi (durvalumab), Enhertu (trastuzumab deruxtecan), datopotamab deruxtecan and savolitinib.

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 April 14, 2021 Wugen Inc., a clinical stage biotechnology company developing a pipeline of allogeneic, off-the-shelf cell therapies, reported the appointment of Daniel M. Kemp Ph.D., as the company’s Chief Executive Officer (Press release, Wugen, APR 14, 2021, View Source [SID1234578030]). Dr. Kemp is an accomplished researcher with over 30 publications and built his career at Novartis, Merck and Takeda over 20 years leading pipeline initiatives from early discovery through to the clinic. More recently, he was responsible for transacting Takeda’s key strategic partnerships in the CAR-NK and CAR-T cell therapy space.

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As CEO of Wugen, Kemp will initially focus on propelling the company’s allogeneic memory NK and CAR-T cell therapy platforms through mid-stage clinical development and continue to build on Wugen’s current strategic partnerships. Dr. John McKearn, the founding Chief Executive Officer of Wugen and a managing director at RiverVest Venture Partners, will remain as Chairman of the Board of Directors.

"We welcome Dan as an experienced strategist with invaluable knowledge of cell therapy development and strong research background. We look forward to him leading the company’s rapid growth and innovative pipeline of cell therapies to treat both hematologic and solid organ malignancies," said John McKearn. "His leadership experience and ability to make good strategic business decisions will be critical to Wugen’s path forward."

Dr. Kemp added, "I am thrilled to be joining such an exceptional team at Wugen. I’m incredibly impressed with how rapidly the company has leveraged its foundational partnerships with Washington University, HCW Biologics and Alpha Biopharma to advance its lead Memory NK cell therapy through clinical proof of concept for relapsed/refractory AML, in addition to advancing its "off-the-shelf" fratricide-resistant CAR-T cell therapy for clinical testing later this year to treat T-cell cancers. I thank John for his trust in me and in the strong foundation that he has created for Wugen."

During his tenure at Takeda, Dr. Kemp was a formative member of the company’s oncology cell therapy leadership team where he transacted a series of cornerstone collaborations that established a pipeline of CAR-NK, CAR-T and gdT cell programs. Notably, Dan spearheaded the in-licensing of Takeda’s flagship allogeneic NK cell program from MD Anderson Cancer Center in late 2019, which consolidated the emergence of NK cell therapies as an important therapeutic platform in the immuno-oncology space. He served on the Boards of GammaDelta Therapeutics and Adaptate Biotherapeutics, both companies that he was instrumental in creating in 2017 and 2019, respectively. Previously, Dr. Kemp was Senior Vice President at Beryllium (acquired by UCB) where he was responsible for directing drug discovery partnerships, and prior to that he directed drug discovery programs at Merck Research Labs ranging from target validation to clinical proof of concept. At Novartis Institutes for BioMedical Research, he led an early discovery team in diabetes and metabolic diseases.

Dr. Kemp received his BSc and Ph.D. in molecular pharmacology from the University of Kent at Canterbury, UK. He was awarded an HHMI Fellowship at Harvard Medical School and carried out his postdoc research on pancreatic beta-cell biology at Massachusetts General Hospital.

On April 14, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported data from an independent, prospective study published in the American Journal of Surgery demonstrating DecisionDx-Melanoma’s utility for prediction of outcomes in patients with cutaneous melanoma (Press release, Castle Biosciences, APR 14, 2021, View Source [SID1234578049]). DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors.

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The publication, titled "Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy," describes a study comparing tumor features, sentinel node biopsy (SLNB) results, and patient outcomes from a prospective database of 383 patients with cutaneous melanoma who both underwent SLNB and had their primary tumor assayed with DecisionDx-Melanoma. Groups were compared by univariate and multivariate analyses, and relapse-free and distant metastasis-free survival (RFS, DMFS) were estimated by Kaplan-Meier method.

The study’s results demonstrated that a Class 2 (high-risk) DecisionDx-Melanoma result was significantly associated with higher rates of SLNB positivity compared to Class 1 (low risk). With respect to risk prognoses, patients who received a Class 2B DecisionDx-Melanoma result and were SLNB-positive experienced the highest recurrence rates (38%), compared to only a 2% recurrence rate for patients who were Class 1A and SLNB-negative. DecisionDx-Melanoma Class 2 results were significantly associated with poorer RFS and DMFS rates compared to Class 1 results, both in the entire cohort of 383 cases and in patients staged as "low risk" (IA-IIA) according to American Joint Committee on Cancer (AJCC) staging criteria.

"We sought to study the utility of this 31 gene expression profile (31-GEP) test in the largest, independent, prospective study to date," said corresponding author John T. Vetto, M.D., FACS, Professor of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland. "Current staging parameters in melanoma are invaluable but also imperfect. We were encouraged to find that, like AJCC stage, the 31-GEP results were independently associated with patient outcomes, including recurrence and distant metastasis, and that the 31-GEP results added prognostic information when incorporated with existing features to evaluate patient risk."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through December 31, 2020, DecisionDx-Melanoma has been ordered more than 68,920 times for use in patients with cutaneous melanoma.

On April 14, 2021 Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that it was notified that CK Hutchison Holdings Limited ("CK Hutchison") shareholding[1] in HUTCHMED remains unchanged, at 332,478,770 ordinary shares of par value US$0.10 each in the capital of HUTCHMED ("Shares") (Press release, Hutchison China MediTech, APR 14, 2021, View Source [SID1234578012]).

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Each American Depositary Share ("ADS") represents five Shares. As announced on April 8, 2021, HUTCHMED issued a total of 16,393,445 Shares (equivalent to 3,278,689 ADSs) to funds affiliated with Baring Private Equity Asia. HUTCHMED was notified on April 14, 2021 that this issuance diluted CK Hutchison’s holding[1] to 44.66 per cent of the total number of voting rights of HUTCHMED. The date on which the notification threshold was crossed was April 14, 2021.

[1] Held through CK Hutchison’s indirect wholly-owned subsidiary Hutchison Healthcare Holdings Limited.

On April 14, 2021 BioAge Labs, Inc. a biotechnology company developing medications that target the molecular causes of aging to extend healthy human life, reported that it has entered into an exclusive worldwide license agreement with Amgen, Inc. [Head Office: Thousand Oaks; CEO: Robert Bradway] to develop and commercialize Amgen’s clinical-stage APJ agonist, BGE-105 (named AMG 986 by Amgen) to ameliorate muscle aging (Press release, BioAge Labs, APR 14, 2021, View Source [SID1234578031]). In older people, muscle aging causes loss of strength, mobility, and function, driving mortality and multiple age-related diseases and decreasing overall quality of life.

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APJ and its natural agonist apelin are components of a signaling pathway that regulates multiple aspects of muscle metabolism, growth, and repair.

BGE-105 is a potent APJ agonist that can be administered orally or intravenously. Phase 1 clinical trials completed in 2019 in 198 subjects who received the drug for up to 21 days showed that BGE-105 had a tolerable safety profile, with acceptable pharmacokinetics (PK) supporting once-daily administration. BioAge’s first clinical trial of BGE-105, planned for initiation in the first quarter of 2022 under the existing IND, will be a Phase 1 study comparing the pharmacodynamic (PD) effects of BGE-105 in humans with those seen in previous trials examining the effects of the apelin peptide.

"BioAge’s advanced proprietary platform comprehensively analyzes longitudinal human data to identify key molecular drivers of aging, which we then validate in preclinical experiments," said Kristen Fortney, PhD, BioAge’s Chief Executive Officer. "Using this robust approach, we found that higher levels of apelin signalling in older people are associated with increased lifespan and reduced symptoms of frailty. Our human-first analysis suggests that the apelin-mimicking drug BGE-105 could recapitulate these positive effects in older patients."

In mice, deficiency in apelin or APJ accelerates loss of muscle function. Consistent with the key roles of apelin–APJ signaling in muscle physiology, BioAge showed in preclinical experiments that BGE-105 increases running wheel activity and other measures of frailty, improves regeneration, and decreases muscle atrophy due to immobilization in old mice.

"Maintaining muscle mass and strength is key to maintaining physical function in the elderly," said Dr. Cedric Dray, an Associate Professor and BioAge collaborator. In 2018, Dr. Dray’s research group discovered that apelin reverses age-associated sarcopenia, and since then has collaborated with BioAge to evaluate BGE-105 in murine models of muscle regeneration. "It is tremendously exciting to trial in humans an oral APJ agonist that recapitulates the positive effects of apelin peptide."

"As with all of BioAge’s clinical assets, BGE-105 is de-risked in two key ways," Fortney said. "First, data from a previous clinical trial show that the molecule was well tolerated in human patients. Second, our human-centric approach reveals that the drug target is physiologically relevant to human aging — in this case, showing that enhancing apelin signaling is compatible with a long and healthy lifespan. This approach maximizes our potential for success and our ability to efficiently deliver solutions to patients for broader, more impactful outcomes."

Under the terms of the license agreement, which covers all indications, BioAge will make an upfront payment to Amgen, who is entitled to receive development and regulatory milestone payments plus royalties based on annual net sales. Amgen will also receive BioAge shares. BioAge will be responsible for all development, manufacturing, and commercialization of BGE-105 worldwide.

"Because it targets a fundamental mechanism of muscle aging, BGE-105 could be used to treat multiple acute and chronic indications, potentially improving muscle strength in frail elderly people, shortening rehabilitation time after hip fracture, or increasing mobility after extended bed rest," Fortney said. "The licensing agreement represents a major milestone toward our vision of developing a pipeline of treatments that separate growing older from disability and disease, dramatically improving the quality of life as we age."