The Lemon Fool

AstraZeneca and MSD's Lynparza (olaparib) has been granted conditional approval in China to treat adult patients with germline or somatic BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following treatment that included a new hormonal agent (abiraterone, enzalutamide).

In China, prostate cancer is the sixth most prevalent cancer in men, with approximately 115,000 new patients diagnosed each year and about 7% have germline BRCA mutations.1,2 Prostate cancer patients with these mutations are more likely to have poorer outcomes than those without the mutations.3 Around 70% of prostate cancer patients in China have advanced disease at the time of diagnosis, and for those with mCRPC, the median survival is less than two years.

AstraZeneca's Biologics License Application (BLA) for tezepelumab has been accepted and granted Priority Review for the treatment of asthma from the US Food and Drug Administration (FDA). Tezepelumab is being developed by AstraZeneca in collaboration with Amgen.

The Food and Drug Administration's (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) has voted 13 to 1 that the benefit-risk profile of roxadustat does not support approval for the treatment of anaemia in chronic kidney disease (CKD) in non-dialysis dependent (NDD) adult patients, and 12 to 2 that the benefit-risk profile of roxadustat does not support approval for the treatment of anaemia in CKD in dialysis-dependent (DD) adult patients.

The FDA will consider the vote, independent opinions and recommendations from experts as it reviews the new drug application (NDA) and is not bound by the Committee's recommendation.

AstraZeneca's Imfinzi (durvalumab) has been approved in China for the 1st-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with standard of care platinum chemotherapy (etoposide plus a choice of either carboplatin or cisplatin).

The approval by China's National Medical Products Administration was based on positive results from the CASPIAN Phase III trial. The trial showed that Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone. In addition, results from the China cohort of patients were consistent with the global results.

Small cell lung cancer (SCLC) is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy.1,2Prognosis is particularly poor, as only 7% of all SCLC patients and 3% of those with extensive-stage disease will be alive five years after diagnosis.3

Opinion based on results from Ultomiris Phase III trial that showed an established efficacy and safety profile with reduced treatment burden for children with PNH and their families

Positive high-level results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), demonstrated superiority over trastuzumab emtansine (T-DM1).

At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that DESTINY-Breast03 met the primary endpoint of progression-free survival (PFS) showing a highly statistically significant and clinically meaningful improvement for patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

Positive high-level results from the PROVENT Phase III pre-exposure prophylaxis trial showed AstraZeneca's AZD7442 achieved a statistically significant reduction in the incidence of symptomatic COVID-19, the trial's primary endpoint.

AZD7442, a combination of two long-acting antibodies (LAAB), reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo. The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis.

There were no cases of severe COVID-19 or COVID-19-related deaths in those treated with AZD7442. In the placebo arm, there were three cases of severe COVID-19, which included two deaths.

Alexion is discontinuing CHAMPION-ALS, the global Phase III clinical trial of Ultomiris (ravulizumab) in adults with amyotrophic lateral sclerosis (ALS).

This decision is based on the recommendation of the Independent Data Monitoring Committee (IDMC), following their review of data from a pre-specified interim analysis. The IDMC recommended that the trial be discontinued due to lack of efficacy. No new safety findings were observed and the data were consistent with the established safety profile of Ultomiris .

ALS is a rare, fatal neurodegenerative disease that affects motor neurons (a type of nerve cell that controls voluntary movements) in the brain and spinal cord.

ALXN1840 FoCus Phase III trial in Wilson disease met primary endpoint demonstrating improvement in copper mobilisation from tissues

ALXN1840 demonstrated approximately three times greater copper mobilisation from tissues than standard-of-care treatments

Positive high-level results from the FoCus Phase III trial in Wilson disease showed ALXN1840 met the primary endpoint with a statistically significant improvement in daily mean copper mobilisation from tissues, demonstrating superiority compared with standard-of-care (SoC) treatments.

Wilson disease is a rare and progressive genetic condition in which the body's pathway for removing excess copper is compromised.1 Damage from toxic copper build-up in tissues and organs leads to liver disease, psychiatric and/or neurological symptoms.1

Forxiga approved in Japan for the treatment of chronic kidney disease in patients with and without type-2 diabetes

Approval marks an important transformation in the treatment of more than 13 million people suffering from chronic kidney disease in Japan

AstraZeneca's Forxiga (dapagliflozin), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been approved in Japan for the treatment of chronic kidney disease (CKD) in adults with and without type-2 diabetes (T2D).

Ultomiris (ravulizumab) has been approved in the European Union for expanded use to include children (with a body weight of 10 kg or above) and adolescents with paroxysmal nocturnal haemoglobinuria (PNH), an ultra-rare and severe blood disorder characterised by the destruction of red blood cells that can cause thrombosis (blood clots) and result in organ damage and potentially premature death.1-4

The approval by the European Commission was based on interim results from the Phase III clinical trial in children and adolescents with PNH that demonstrated the safety and efficacy of Ultomiris in these patients.

Fixed-dose combination of albuterol and budesonide (PT027) demonstrated significant benefits for asthma patients in MANDALA and DENALI Phase III trials

PT027 significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma in MANDALA trial when used as a rescue medicine in response to symptoms

PT027 significantly improved lung function compared to individual components in mild to moderate asthma in DENALI trial.

Detailed positive results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), demonstrated superior progression-free survival (PFS) versus trastuzumab emtansine (T-DM1), a HER2-directed ADC currently approved to treat patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. Results were presented today in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2021.

idpickering wrote:Enhertu reduced risk of disease progression by 72%

Detailed positive results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), demonstrated superior progression-free survival (PFS) versus trastuzumab emtansine (T-DM1), a HER2-directed ADC currently approved to treat patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. Results were presented today in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2021.

https://www.investegate.co.uk/astrazene ... 00082734M/

Bouleversee wrote:

idpickering wrote:Enhertu reduced risk of disease progression by 72%

Detailed positive results from the head-to-head DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), demonstrated superior progression-free survival (PFS) versus trastuzumab emtansine (T-DM1), a HER2-directed ADC currently approved to treat patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. Results were presented today in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2021.

https://www.investegate.co.uk/astrazene ... 00082734M/

According to articles in the Sunday Times, AZ is set to make billions from this cancer cure. However, it can only be used for patients whose cancer produces a protein, Her2, which accelerates the growth of the disease but apparently only about a 5th of women with breast cancer have this mutation. This is probably why the s.p. has only gone up about 3% this morning, still some way short of what I paid for my last top up some months ago.

Positive high-level results from the PROpel Phase III trial showed AstraZeneca and MSD's Lynparza (olaparib) in combination with abiraterone demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) versus standard-of-care abiraterone as a 1st-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations.

At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that the trial met the primary endpoint of rPFS in men with mCRPC who had not received treatment in the 1st-line setting including with new hormonal agents (NHAs) or chemotherapy.

The trial also showed a trend at this interim analysis towards improved overall survival (OS). However, the data are still immature and the trial will continue to assess OS as a key secondary endpoint. The safety and tolerability were consistent with the known profiles of each medicine.

AstraZeneca's Saphnelo (anifrolumab) has been approved in Japan for the treatment of adult patients with systemic lupus erythematosus (SLE), a serious autoimmune disease, who show insufficient response to currently available treatment.

The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was based on efficacy and safety data from the Saphnelo clinical development programme, including the TULIP Phase III trials and the MUSE Phase II trial. In these trials, more patients treated with Saphnelo experienced a reduction in overall disease activity across organ systems, including skin and joints, and achieved sustained reduction in oral corticosteroid (OCS) use compared to placebo, with both groups receiving standard therapy.1,2,3

AstraZeneca's Alexion has exercised its option to acquire all remaining equity in Caelum Biosciences for CAEL-101, a potentially first-in-class fibril-reactive monoclonal antibody (mAb) for the treatment of light chain (AL) amyloidosis.

AL amyloidosis is a rare disease in which misfolded amyloid proteins build up in organs throughout the body, including the heart and kidneys, causing significant organ damage and failure that may ultimately be fatal. 1,2 Approximately 20,000 people across the US, France, Germany, Italy, Spain and the UK live with AL amyloidosis classified as Mayo stage IIIa or IIIb disease.3

The Food and Drug Administration (FDA) has granted Enhertu (trastuzumab deruxtecan), Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens. Enhertu is a HER2-directed antibody drug conjugate (ADC) jointly developed by AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo).

The FDA granted BTD based on data from the DESTINY-Breast03 Phase III trial presented during the European Society for Medical Oncology (ESMO) Congress 2021. This is the second BTD for Enhertu in breast cancer and now brings the total number of BTDs to four for this medicine.

Positive high-level results from the TACKLE Phase III COVID-19 treatment trial showed AstraZeneca's AZD7442, a long acting antibody (LAAB) combination, achieved a statistically significant reduction in severe COVID-19 or death compared to placebo in non-hospitalised patients with mild-to-moderate symptomatic COVID-19.

The trial met the primary endpoint, with a dose of 600mg of AZD7442 given by intramuscular (IM) injection reducing the risk of developing severe COVID-19 or death (from any cause) by 50% compared to placebo in outpatients who had been symptomatic for seven days or less. The trial recorded 18 events in the AZD7442 arm (18/407) and 37 in the placebo arm (37/415). The LAAB was generally well tolerated in the trial.

In a prespecified analysis of participants who received treatment within five days of symptom onset, AZD7442 reduced the risk of developing severe COVID-19 or death (from any cause) by 67% compared to placebo, with nine events in the AZD7442 arm (9/253) and 27 in the placebo arm (27/251).

AZD7442 is the first LAAB with Phase III data to demonstrate benefit in both prophylaxis and treatment of COVID-19 and is easily administered by IM injection.

AstraZeneca will be discussing the data with health authorities. On 5 October 2021, the Company announced that it had submitted a request to the US Food and Drug Administration for Emergency Use Authorisation for AZD7442 for prophylaxis of COVID-19.