AstraZeneca PLC (AZN)

[idpickering]

Ultomiris approved in EU for gMG.

Ultomiris (ravulizumab) has been approved in Europe as an add-on to standard therapy for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.

This decision marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of gMG in Europe. gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.1 The diagnosed prevalence of gMG in the EU is estimated at approximately 89,000.2-8

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the CHAMPION-MG Phase III trial, which were published online in NEJM Evidence. In the trial, Ultomiris was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients' abilities to perform daily activities.9 Additionally, in prolonged follow-up results from the open-label extension, clinical benefit of Ultomiris was observed through 60 weeks.

https://www.investegate.co.uk/astrazene ... 00084292A/

Ian.

[idpickering]

Tezspire approved in Japan for severe asthma.

AstraZeneca's Tezspire (tezepelumab) has been approved in Japan for the treatment of bronchial asthma in patients with severe or refractory disease in whom asthma symptoms cannot be controlled with mid- or high-dose inhaled corticosteroids and other long-term maintenance therapies.1

The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was based on efficacy and safety results from the PATHFINDER clinical trial programme. The application included results from the pivotal NAVIGATOR Phase III trial in which Tezspire demonstrated superiority across every primary and key secondary endpoint in patients with severe asthma, compared to placebo, when added to standard therapy.2

https://www.investegate.co.uk/astrazene ... 00076973A/

Ian.

[idpickering]

Koselugo approved in Japan for NF1.

Koselugo (selumetinib) has been approved in Japan for the treatment of paediatric patients three years of age and older with plexiform neurofibromas (PNs) in neurofibromatosis type 1 (NF1) with clinical symptoms, such as pain and disfigurement, and PNs which cannot be completely removed by surgery without risk of substantial morbidity. 1

The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) is based on positive results from the SPRINT Stratum 1 Phase II trial sponsored by the National Institutes of Health's National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP). The trial showed Koselugo, an oral treatment option, reduced the size of inoperable tumours in children.1,2 Additionally, a Phase I trial in Japanese paediatric NF1 patients with symptomatic and inoperable PNs was also evaluated as a basis for the approval, with the trial showing tumour reduction.

https://www.investegate.co.uk/astrazene ... 05058019A/

Ian.

[idpickering]

Covid: hopes for Oxford nasal vaccine dealt blow after poor trial results.

Scientists ditch plans to develop nasal spray version of Oxford/AstraZeneca vaccine in its current form.

Hopes of distributing the Oxford/AstraZeneca Covid vaccine as a nasal spray have been dealt a blow after researchers said it performed poorly in its first clinical trial.

The underwhelming results have led scientists to abandon plans to develop the spray in its current form, with hopes now resting on different formulations of the vaccine and more complex delivery devices, such as nebulisers that can deliver medicines deep into the lungs.

“The nasal spray did not perform as well in this study as we had hoped,” said Dr Sandy Douglas, the chief investigator on the trial at Oxford’s Jenner Institute. “Delivery of vaccines to the nose and lungs remains a promising approach, but this study suggests there are likely to

https://www.theguardian.com/world/2022/ ... neca-trial

nb. I haven't seen a RNS from AZN on this as yet?

Ian.

[idpickering]

Imfinzi + Imjudo approved in advanced liver cancer.

AstraZeneca's Imjudo (tremelimumab) in combination with Imfinzi (durvalumab) has been approved in the US for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer. The novel dose and schedule of the combination, which includes a single dose of the anti-CTLA-4 antibody Imjudo 300mg added to the anti-PD-L1 antibody Imfinzi 1500mg followed by Imfinzi every four weeks, is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).

The approval by the US Food and Drug Administration (FDA) was based on positive results from the HIMALAYA Phase III trial. In this trial, patients treated with the combination of Imjudo and Imfinzi experienced a 22% reduction in the risk of death versus sorafenib (based on a hazard ratio [HR] of 0.78, 95% confidence interval [CI] 0.66-0.92 p=0.0035).1 Results were also published in theNew England Journal of Medicine Evidenceshowing that an estimated 31% of patients treated with the combination were still alive after three years, with 20% of patients treated with sorafenib still alive at the same duration of follow-up.2

Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.3,4 It is the fastest rising cause of cancer-related deaths in the US, with approximately 36,000 new diagnoses each year.5,6

https://www.investegate.co.uk/astrazene ... 00098408D/

Ian.

[idpickering]

Update on the MESSINA Phase III trial for Fasenra in eosinophilic esophagitis.

MESSINA did not meet one of the two dual-primary endpoints, demonstrating a statistically significant improvement in histological disease remission with Fasenra, but not in dysphagia symptoms, compared to placebo.

https://www.investegate.co.uk/astrazene ... 00069492D/

Ian.

[idpickering]

Capivasertib Phase III trial met primary endpoints.

Positive high-level results from the CAPItello-291 Phase III trial showed that AstraZeneca's capivasertib in combination with Faslodex (fulvestrant) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus placebo plusFaslodexin patients with hormone receptor (HR)-positive,human epidermal growth factor receptor 2 (HER2)-low or negative locally advanced or metastatic breast cancer,following recurrence or progression on or after endocrine therapy (with or without a CDK4/6 inhibitor).

https://www.investegate.co.uk/astrazene ... 00051531E/

Ian.

[idpickering]

Beyfortus (nirsevimab) approved in EU.

AstraZeneca and Sanofi's Beyfortus (nirsevimab) has been approved in the European Union (EU) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season.1Beyfortus is the first and only single-dose RSV passive immunisation for the broad infant population, including those born healthy, at term or preterm, or with specific health conditions.

RSV is a common and highly contagious seasonal virus, infecting nearly all children by the age of two.2,3

The European Commission is the first regulatory body to grant approval to Beyfortus.1 The approval was based on results from the Beyfortus clinical development programme, including the MELODY Phase III, MEDLEY Phase II/III and Phase IIb trials,1,4-11and follows the recommendation by The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency in September 2022.12

https://www.investegate.co.uk/astrazene ... 00032942F/

Ian.

[idpickering]

FDA Advisory Committee recommends PT027 in asthma.

The Food and Drug Administration's (FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) has voted 16 to 1 that the data support a favourable benefit risk assessment for the use of PT027 (albuterol/budesonide) for the treatment of asthma in people aged 18 years and older. In adolescents aged 12 to 17 years, the Committee voted 9 to 8 that the data do not support a favourable benefit risk assessment for the use of PT027 for the treatment of asthma. In children aged 4 to 11 years, the Committee voted 16 to 1 that the data do not support a favourable benefit risk assessment for the use of PT027 for the treatment of asthma.

https://www.investegate.co.uk/astrazene ... 00088048F/

Ian.

[idpickering]

YTD and Q3 2022 Results.

‒ Total Revenue increased 37% to $33,144m, with growth coming from all disease areas, and from the addition of Alexion, which was incorporated into the Group's results from 21 July 2021

‒ Oncology Total Revenue increased 24%, inclusive of milestone payments from MSD[6] for Lynparza. Oncology Product Sales increased 20%. Total Revenue from R&I[7] increased 4%, CVRM[8] increased 19%[9] and Rare Disease increased 10%9

‒ Core Gross Margin of 81%, up six percentage points at CER, reflecting the lower revenue from initial Vaxzevria contracts and the increased share of specialty care medicines

‒ Core Total Operating Expense increased 26%, reflecting the addition of Alexion, continued investment in new launches and the pipeline, to deliver sustainable long-term growth

‒ Core Operating Margin of 32%, up six percentage points at CER, benefitting from favourable phasing and product mix

‒ Core EPS increased 52% to $5.28

‒ FY 2022 Core EPS at constant exchange rates now expected to increase by a high twenties to low thirties percentage, vs previous guidance of a mid-to-high twenties increase. At actual exchange rates, FY 2022 Core EPS growth is anticipated to be impacted by a currency headwind[10] of a mid-to-high single-digit percentage, versus previous guidance of a mid single-digit headwind

Key milestones achieved since the prior results

‒ Key data: Positive Phase III read-outs for danicopan in PNH-EVH[11] (ALPHA) and for capivasertib in 2nd-line HR-positive, metastatic breast cancer (CAPItello-291)

‒ Key regulatory approvals: 19 approvals in major markets since H1 2022 results, including US approvals for Enhertu in HER2[12]-low breast cancer (DESTINY-Breast04) and advanced NSCLC[13] (DESTINY-Lung02), Imjudo and Imfinzi in advanced liver cancer (HIMALAYA), Imfinzi in advanced biliary tract cancer (TOPAZ‑1); EU approval for Beyfortus for the prevention of RSV[14] lower respiratory tract disease (MELODY/MEDLEY); EU and Japan approvals for Ultomiris in gMG[15] (CHAMPION-MG), Tezspire in severe asthma (NAVIGATOR) and Lynparza in early breast cancer (OlympiA)

‒ Other regulatory milestones: US Priority Review for Lynparza for 1st-line metastatic castration-resistant prostate cancer (PROpel)

Pascal Soriot, Chief Executive Officer, AstraZeneca, said:

"AstraZeneca continues to see the benefit of our sustained investment in R&D, with 19 major regulatory approvals since our last earnings call.

After a strong performance in the year to date, we have increased our Core EPS guidance for the full year 2022. Additionally, recent encouraging data for several of our pipeline programmes have given us the confidence to proceed with additional late-stage clinical trials as we maintain our focus on delivery of our growth ambitions.

I would also like to highlight the announcement at COP27 to accelerate the delivery of our net zero strategy. Our company intends to lead by example on this increasingly important objective for the world."

https://www.investegate.co.uk/astrazene ... 00069054F/

Ian.

[idpickering]

Imfinzi and Imjudo with chemotherapy approved in the US for patients with metastatic non-small cell lung cancer.

AstraZeneca's Imfinzi (durvalumab) in combination with Imjudo (tremelimumab) plus platinum-based chemotherapy has been approved in the US for the treatment of adult patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).

https://www.investegate.co.uk/astrazene ... 00060665G/

Ian.

[idpickering]

Lynparza combo recommended in the EU for mCRPC.

Lynparza in combination with abiraterone recommended for approval
in the EU by CHMP as 1st-line treatment for patients
with metastatic castration-resistant prostate cancer.

https://www.investegate.co.uk/astrazene ... 00062233G/

Ian.

[idpickering]

Imfinzi recommended for approval in the EU for BTC.

Imfinzi plus chemotherapy recommended for approval in the EU by CHMP
as first immunotherapy regimen for advanced biliary tract cancer

https://www.investegate.co.uk/astrazene ... 05052234G/

Ian.

[idpickering]

Enhertu recommended for EU approval in gastric cancer.

Enhertu recommended for approval in the EU by CHMP for patients with previously treated HER2-positive advanced gastric cancer.

https://www.investegate.co.uk/astrazene ... 10052237G/

Ian.

[idpickering]

AstraZeneca to acquire Neogene Therapeutics.

AstraZeneca today announced an agreement to acquire Neogene Therapeutics Inc. (Neogene), a global clinical-stage biotechnology company pioneering the discovery, development and manufacturing of next-generation T-cell receptor therapies (TCR-Ts) that offer a novel cell therapy approach for targeting cancer.

With a shared goal of bringing cell therapies to patients with solid tumours, Neogene's expertise in TCR-T discovery, development and manufacturing will strengthen AstraZeneca's ambition to transform outcomes for patients.

TCR-Ts are emerging as a promising therapeutic modality in cancer treatment. Most current cell therapy approaches in oncology focus on modifying the immune system's T cells to recognise proteins expressed on the surface of cancer cells. In contrast, TCR-Ts can recognise intracellular targets, including cancer-specific mutations, thereby potentially unlocking targets previously inaccessible using cell therapies.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "This acquisition represents a unique opportunity to bring innovative science and leading experts in T-cell receptor biology and cell therapy manufacturing together with our internal oncology cell therapy team, unlocking new ways to target cancer. Neogene's leading TCR discovery capabilities and extensive manufacturing experience complement the cell therapy capability we have built over the last three years and allow us to accelerate the development of potentially curative cell therapies for the benefit of patients."

Carsten Linnemann, PhD, Chief Executive Officer, Neogene, said: "We are excited to work together with AstraZeneca towards our shared mission of transforming the treatment options for patients with solid tumours using next-generation T-cell receptor therapies. Our expertise, clinical portfolio and platform technologies in this area combined with AstraZeneca's leadership in oncology and global footprint mean we are well-positioned to translate pioneering science into novel treatments for hard-to-treat cancers."

Neogene will operate as a wholly owned subsidiary of AstraZeneca, with operations in Amsterdam, the Netherlands and California, US.

Financial considerations

AstraZeneca will acquire all outstanding equity of Neogene for a total consideration of up to $320m, on a cash and debt free basis. This will include an initial payment of $200m on deal closing, and a further up to $120m in both contingent milestones-based and non-contingent consideration.
The transaction is expected to close in the first quarter of 2023, subject to customary closing conditions and regulatory clearances. The transaction does not impact AstraZeneca's financial guidance for 2022.

https://www.investegate.co.uk/astrazene ... 00069010H/

Ian.

[idpickering]

AstraZeneca announces sale of its West Chester, Ohio (US) manufacturing site.

AstraZeneca today announces the sale of its West Chester site in Ohio, US, to National Resilience, Inc. (Resilience), a technology-focused manufacturing company dedicated to broadening access to complex medicines.

Andrew Wirths, Senior Vice President, Americas Supply Region, AstraZeneca, said: "As part of our long-term strategy to ensure our global supply network remains fit for the future, we are continuously optimising our manufacturing footprint to meet the evolving needs of our pipeline and portfolio. The transfer of our West Chester site to Resilience will enable the continued supply of AstraZeneca medicines to patients, as well as the continued employment for more than 500 people working at the West Chester site. I'm encouraged by Resilience's plans to transform the site into their drug product centre of excellence."

"The West Chester site will play an important role in the delivery of our mission to broaden access to complex medicines, protect biopharmaceutical supply chains, and strengthen domestic preparedness," said Rahul Singhvi, Sc.D, Chief Executive Officer of Resilience. "I'm confident that West Chester's premier capabilities, including the talented employees who are joining Resilience, will help us expand our business in new directions."

AstraZeneca expects to complete the sale in the first quarter of 2023, with a phased transition of services.

https://www.investegate.co.uk/astrazene ... 05019775H/

Ian.

[idpickering]

Update on US review of Lynparza PROpel sNDA.

AstraZeneca and MSD today announced that the US Food and Drug Administration (FDA) has informed AstraZeneca that it will extend the Prescription Drug User Fee Act (PDUFA) dateby three months to provide further time for a full review ofthe supplementary new drug application (sNDA) for Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone for the treatment ofmetastatic castration-resistant prostate cancer (mCRPC). The companies will continue to work with the FDA to facilitate the completion of the agency's review.

The sNDA is based on results from thepivotal PROpel Phase III trial, which were published in June 2022 in NEJM Evidence. In August 2022, the sNDA was granted Priority Review and AstraZeneca and MSD are committed to working with the FDA to bring this treatment option to patients with mCRPC.

In November, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of Lynparza in combination with abiraterone and prednisone or prednisolone in the EU for the treatment of adult patients with mCRPC for whom chemotherapy is not clinically indicated. This combination is also undergoing regulatory reviews in other countries.

Lynparza is approved in the US based on results from the PROfound Phase III trial as monotherapy for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan, and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent.

https://www.investegate.co.uk/astrazene ... 00027574J/

Ian.

[idpickering]

Imfinzi + Imjudo recommended for approvals in EU.

AstraZeneca's Imfinzi (durvalumab) and Imjudo (tremelimumab) combinations have been recommended for marketing authorisation in the European Union (EU) for advanced liver and lung cancers.

The concurrent positive opinions recommend authorising Imfinzi in combination with Imjudofor 1st-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC); andImfinzi in combination with Imjudoand platinum-based chemotherapy for the treatment of adult patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinions on results from theHIMALAYAPhase III trial, which was published intheNew England Journal of Medicine Evidence, and results from thePOSEIDON Phase III trial, which was published in theJournal of Clinical Oncology.

Bruno Sangro, MD, PhD, Director of the Liver Unit at Clínica Universidad de Navarra, Professor of Internal Medicine at the University of Navarra School of Medicine and a lead investigator in the HIMALAYA trial, said: "Liver cancer is a leading cause of cancer death in Europe, and patients with advanced disease face an especially grim prognosis with limited treatment options in the 1st-line setting. The combination of Imjudo and Imfinzi demonstrated a meaningful improvement in overall survival with no increase in severe liver toxicity or bleeding risk, which are important considerations for these patients who often have advanced disease."

https://www.investegate.co.uk/astrazene ... 10040761K/

I hold.

Ian.

[idpickering]

Update on Imfinzi PEARL trial.

The PEARL Phase III trial for AstraZeneca's Imfinzi (durvalumab) did not achieve statistical significance for the primary endpoints of improving overall survival (OS) versus platinum-based chemotherapy as a monotherapy treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC) whose tumour cells express high levels (25% or more) of PD-L1, or in a subgroup of patients at low risk of early mortality. There was an improvement in OS with Imfinzi monotherapy, which was clinically meaningful in the subset of patients with PD-L1 tumour expression greater than 50%, a secondary endpoint. The trial was conducted primarily in Asia.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "With PEARL, we set out to answer important scientific questions in the treatment of metastatic non-small cell lung cancer at a time when patient selection for immune checkpoint inhibitors was still evolving. We are encouraged to see patients in the metastatic setting at a higher level of PD-L1 tumour expression demonstrate the most benefit with Imfinzi monotherapy treatment, as is commonly seen in this class. We remain steadfast in our dedication to developing new and improved medicines and regimens for patients with lung cancer across our diverse portfolio."

https://www.investegate.co.uk/astrazene ... 05030760K/

I hold.

Ian.

[idpickering]

Forxiga recommended for approval in the EU by CHMP for symptomatic chronic heart failure.

AstraZeneca's Forxiga (dapagliflozin) has been recommended for approval in the European Union (EU) to extend the indication for heart failure with reduced ejection fraction (HFrEF) to cover patients across the full spectrum of left ventricular ejection fraction (LVEF) including HF with mildly reduced and preserved ejection fraction (HFmrEF, HFpEF).

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the DELIVER Phase III trial, published in The New England Journal of Medicine 1 and results from a pre-specified, patient level, pooled analysis of the DAPA-HF and DELIVER Phase III trials published in Nature Medicine 2 . The pooled analysis showed Forxigato be the first HF medication to demonstrate mortality benefit across the full ejection fraction range3.

HF is a life-threatening chronic disease in which the heart cannot pump enough blood around the body4, affecting 15 million people in the EU5 . Patients with HFmrEF or HFpEF experience an especially high burden of symptoms and physical limitations, and a poor quality of life, which is why improving health status is a key goal of management6.

https://www.investegate.co.uk/astrazene ... 00060759K/

I hold.

Ian.