AstraZeneca 2021: Not just a vaccine

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Tagrisso

AstraZeneca produced one of the global vaccines to treat COVID-19, but the company’s growth in the future will still rely on the oncology and respiratory areas.

By Christiane Truelove • [email protected]

 

 

 

 

AstraZeneca

1 Francis Crick Avenue, Cambridge Biomedical Campus

Cambridge CB2 0AA, UK

Telephone: +44 (0)20 3749 5000

Website: astrazeneca.com

 

OUTCOMES CREATIVITY INDEX SCORE: 39

Manny Awards — 2

Cannes Lions — 4

Clio Health — 4 

Creative Floor Awards — 20  

MM+M Awards — 3 

One Show — N/A 

 

Financial Performance

(All figures are in millions of dollars, except EPS.)

2020 

Revenue $26,617  

Net income $3,144  

Diluted EPS $2.44  

R&D expense $5,991  

1H 2021  

Revenue $15,540  

Net income $2,112  

Diluted EPS $1.61  

R&D expense $3,542  

 

Best-Selling Products

2020

(All sales are in millions of dollars.)

Tagrisso $4,328 

Symbicort $2,721  

Imfinzi $2,042  

Farxiga $1,959 

Lynparza $1,776  

Brilinta $1,593  

Nexium $1,492 

Crestor $1,180  

Pulmicort $996  

Fasenra $949  

Zoladex $888  

Toprol-XL/Seloken $821  

Faslodex $580  

Calquence $522  

1H 2021  

Tagrisso $2,454  

Symbicort $1,371       

Farxiga $1,359  

Vaxzevria $1,169  

Imfinzi $1,160  

Lynparza $1,131  

Brilinta $749  

Nexium $739  

Fasenra $580  

Crestor $539  

Toprol-XL/Seloken $515  

Pulmicort $497  

Calquence $490 

Zoladex $466  

 

 

AstraZeneca achieved many of its goals in 2020, and continues to mark milestones in 2021, according to the company’s leadership team.

“I am proud of everyone in AstraZeneca who achieved so much in the face of the biggest health crisis the world has encountered in more than a generation. I am even more proud of the fact that, despite the pandemic, employees worked tirelessly to ensure the safety of patients, and their continued access to care and medicines.” — CEO Pascal Soriot

“Despite the impact of the COVID-19 pandemic, our performance in 2020 ensured that we were able to continue delivering value for patients and shareholders as well as for society,” states CEO Pascal Soriot.

According to Soriot, the value the company delivered in 2020 was made possible through the progress it made against all its strategic priorities and across the whole organization. “I am proud of everyone in AstraZeneca who achieved so much in the face of the biggest health crisis the world has encountered in more than a generation,” Soriot says. “I am even more proud of the fact that, despite the pandemic, employees worked tirelessly to ensure the safety of patients, and their continued access to care and medicines.” 

Soriot continues, “We also focused on protecting our staff and critical operations. Working with partners across the world, we played a leading role in the process of scientific innovation to combat the virus and contributed more broadly to society, including with emergency relief.”

AstraZeneca and COVID-19

AstraZeneca teamed with the University of Oxford’s spinout company, Vaccitech, to produce a COVID-19 vaccine. In January the vaccine, now known as Vaxzevria, was recommended for conditional marketing authorization (CMA) in the European Union for active immunization to prevent COVID-19 caused by SARS-CoV-2, in individuals 18 years of age and older.

Following review of the application, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on data from a rolling review of trial data from the primary analysis of the Phase III program led by the University of Oxford. 

The vaccine uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

In February, the vaccine was authorized for emergency use by the World Health Organization. AstraZeneca committed to making the vaccine available to as many countries as possible and at no profit during the pandemic period. In June 2020, the company announced a sub-licensing agreement with the Serum Institute of India (SII) to manufacture and supply up to 1 billion doses of the vaccine to low and middle-income countries. The WHO approval was based on pooled analysis for efficacy from 11,636 participants aged 18 years and older, accruing 131 symptomatic COVID-19 infections from the UK and Brazil Phase III trials conducted by Oxford University.

By March, however, there were reports of blood clotting in some of the recipients of the vaccine two weeks after vaccination. 

In April, EMA’s safety committee (PRAC) concluded that unusual blood clots with low blood platelets should be listed as very rare side effects of Vaxzevria, and that the benefits of vaccination outweighed the risks.

The vaccine was further vindicated in July when in a large real-world study – data published as a pre-print on The Lancet server from more than 1 million individuals – assessed the incidence rates of blood clotting disorders of thromboembolism and thrombocytopenia, including the very rare thrombosis with thrombocytopenia (TTS) following vaccination with an mRNA vaccine or Vaxzevria, and compared them with expected rates in a general population and in people with COVID-19.

The study found that safety profiles of Vaxzevria and the mRNA-based vaccine were similar and overall favorable. Although very rare clotting disorders (TTS) were observed with both vaccines, these were in line with what would be expected in the general population and lower than in those diagnosed with COVID-19. 

Regardless of the vaccine used, the increase in rates of thrombosis among persons infected with COVID-19 was far higher than among those vaccinated, AstraZeneca stated. The rates of venous thromboembolism were eight times higher after a diagnosis of COVID-19 infection compared with the expected rate.

“This real-world study offers further evidence of the favorable benefit:risk profile of Vaxzevria and demonstrates the critical role all COVID-19 vaccines are playing in combating the pandemic,” says Sir Mene Pangalos, executive VP, BioPharmaceuticals R&D, AstraZeneca.

In September, AstraZeneca and the European Commission reached an agreement that ends legal proceedings over the execution of the Advance Purchase Agreement for the delivery of Vaxzevria. This brought to an end legal proceedings that were initiated in April.

Under the agreement, AstraZeneca commits to deliver 60 million doses of the vaccine by the end of third-quarter 2021, 75 million by the end of fourth-quarter 2021 and 65 million by the end of first-quarter 2022. EU Member States will be provided with regular delivery schedules, and capped rebates will apply in the event of any delayed doses.

“I’m very pleased that we have been able to reach a common understanding which allows us to move forward and work in collaboration with the European Commission to help overcome the pandemic,” says Ruud Dobber, executive VP, BioPharmaceuticals Business Unit, AstraZeneca. “We are fully committed to manufacture Vaxzevria for Europe following the release for supply of more than 140 million doses to date at no profit. We are also looking forward to working with the European Commission in a joint effort to further support COVAX.”

By the end of the first half of 2021, sales of Vaxzevria were $1.17 billion. 

In September, the company announced that it had joined the European Respiratory Society (ERS), the Global Allergy and Airways Patient Platform (GAAPP), Amgen and leading respiratory clinicians to launch the International Respiratory Coalition, a new partnership to transform post-pandemic respiratory healthcare.

The Coalition aims to support governments and healthcare systems in their recovery from COVID-19 by strengthening respiratory care, and will seek to improve outcomes for people living with respiratory diseases by supporting the creation of ambitious national-level respiratory strategies and by building resilience in managing pandemics. 

According to the group’s organizers, prior to the pandemic, progress to improve chronic respiratory diseases care was slow, and in some countries had stagnated over the past decade. During the pandemic, some patients with chronic respiratory diseases who contracted COVID-19 were shown to be at greater risk of hospitalizations. In addition, patients with chronic respiratory diseases faced disruptions to healthcare services and quality care, demonstrating new approaches to enable patients to better control their condition, reduce hospitalizations, and ultimately decrease pressure on healthcare systems, are needed.

“The International Respiratory Coalition has an important opportunity to reduce morbidity and mortality in respiratory disease while building healthcare system resilience,” Dobber says. “AstraZeneca has been committed to advancing respiratory science and care for more than 50 years and we are excited to contribute to this important initiative to support patients who are underserved today.”

Alexion Acquisition

The company announced in December 2020 that AstraZeneca and Alexion had entered into a definitive acquisition agreement. 

“Alexion has established itself as a leader in complement biology, bringing life-changing benefits to patients with rare diseases,” Soriot stated at the time. “This acquisition allows us to enhance our presence in immunology.”

Executives say the acquisition will help AstraZeneca establish a presence in rare diseases, which represent a high-growth area with rapid innovation and significant unmet medical need. Alexion has five marketed products: Soliris, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS); Ultomiris, a humanized monoclonal antibody complement inhibitor medication designed for the treatment of PNH and aHUS; Strensiq, for treating perinatal/infantile-onset and juvenile-onset hypophosphatasia (HPP); Kanuma, a recombinant form of the enzyme lysosomal acid lipase that is used as a medication for the treatment of lysosomal acid lipase deficiency; and Andexxa, an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. 

AstraZeneca received U.S. clearance for the acquisition in April, and shareholders voted in favor of the deal during May. The UK’s Competition and Markets Authority gave authorization during July, and the acquisition was completed during that month. The total consideration paid to Alexion’s shareholders amounted to $13.3 billion in cash and 236,321,411 new AstraZeneca shares (94 percent of which will be represented by new AstraZeneca American Depositary Shares).  

AstraZeneca executives say total revenue for full-year 2021 is expected to increase by a low-twenties percentage, accompanied by a faster growth in Core EPS to $5.05 to $5.40.

The acquisition also caused some shifts in management. In August, Aradhana Sarin, previously executive VP and chief financial officer of Alexion, was appointed executive director and chief financial officer of AstraZeneca. In addition, Marc Dunoyer stepped down as chief financial officer of AstraZeneca, retiring from the company’s board, and becoming CEO of Alexion and chief strategy officer of AstraZeneca. Dunoyer continues to report to Soriot and remains a member of AstraZeneca’s senior executive team.

As this magazine was going to press, AstraZeneca’s Alexion on Sept. 29 exercised the option to acquire all remaining equity in Caelum Biosciences for CAEL-101, a potentially first-in-class fibril-reactive monoclonal antibody for the treatment of light chain amyloidosis.

Performance & Outlook

“We delivered strong results in 2020, despite the adverse impact of the pandemic,” Soriot says. Revenue last year amounted to $26.62 billion, 9.2 percent more than in 2019. Profit after tax was $3.14 billion compared with $1.23 billion in the prior year, and earnings per share were $2.44 compared with $1.03.

The company’s financial performance continued strongly in the first half of 2021, with revenue of $15.54 billion, 23 percent higher than in the same period last year. Net income was $2.11 billion, an increase of 42 percent, and earnings per share were $1.61, 37 percent more compared with the same period in 2020. Soriot attributed the growth to strong performances across all regions and disease areas, particularly Oncology, New CVRM, and Fasenra in Respiratory.

Tagrisso is AstraZeneca’s top-selling medicine, with first-half 2021 sales coming in at $2.45 billion. Tagrisso has received regulatory approval for the first-line treatment of patients with epidermal growth factor receptor-mutated non-small cell lung cancer in 91 countries and as an adjuvant treatment for EGFRm NSCLC patients in 56 countries.

AstraZeneca’s leading product in 2020 was Tagrisso, a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor approved in lung cancer. The drug achieved sales of $4.33 billion, 36 percent more than in 2019. In first-half 2021, Tagrisso sales were $2.45 billion, 22 percent more than in first-half 2020.

No. 2 in sales was the asthma drug Symbicort, which generated $2.72 billion in 2020, an increase of 9 percent from 2019. First-half 2021 sales were $1.37 billion, 5 percent less than in the comparable period last year.

Third in 2020 product sales is the cancer drug Imfinzi, which generated $2.04 billion compared with $1.47 billion in 2019. Sales in the first half of 2021 totaled $1.16 billion, 22 percent more than in first-half 2020.

Farxiga was approved in the United States during April 2021 for the treatment of chronic kidney disease in patients at risk of progression with and without type 2 diabetes. According to AstraZeneca, the approval of the sodium-glucose cotransporter 2 (SGLT2) inhibitor is the most significant advancement in the treatment of chronic kidney disease in more than 20 years.

No. 4 in sales is the cardiovascular drug Farxiga, which had sales of $1.96 billion, 27 percent more than in 2019. Sales in first-half 2021 also showed growth, at $1.36 billion, 60 percent more than in first-half 2020.

Lynparza, the first-in-class PARP inhibitor approved in ovarian, breast, prostate and pancreatic cancers, was the company’s fifth best-selling drug. Sales reached $1.78 billion in 2020, 48 percent more than in 2019. First-half 2021 sales were recorded at $1.13 billion, an increase of 39 percent compared with same-period 2020.

AstraZeneca’s sixth best-selling drug in 2020 was the blood thinner Brilinta, which generated $1.59 billion, about the same as in 2019. In the first half of 2021 sales were $749 million, 11 percent less than in the same period last year.

Nexium sales during 2020 totaled $1.49 billion, up 1 percent year-over-year. First-half 2021 sales for the proton pump inhibitor for treating acid-related diseases amounted to $739 million, increasing 4 percent versus the 2020 first half.

Sales for the cholesterol drug Crestor declined 10 percent in 2020 to $1.18 billion. Crestor’s sales in first-half 2021 also declined in comparison with first-half 2020, down 7 percent to $539 million.

Sales in 2020 for the asthma drug Pulmicort declined 32 percent from 2019 to $996 million. Sales in the first half of this year were $497 million, 4 percent more than in the same period of 2020.

The respiratory drug Fasenra generated $949 million compared with $704 million in 2019. The product continued the sales climb in first-half 2021 with $580 million, 36 percent more than in the first six months of 2020.

The oncology drug Zoladex produced 2020 sales of $888 million compared with $813 million the previous year. Sales in the first half of 2021 were $466 million, 5 percent more than in first-half 2020.

AstraZeneca’s blood pressure medication Toprol-XL/Seloken posted $821 million in 2020 sales, climbing 8 percent from 2019. First-half 2021 sales amounted to $515 million, 30 percent more than in the same period during 2020.

AstraZeneca’s cancer drug Faslodex recorded $580 million for 2020 compared with $892 million in 2019. First-half 2021 sales were $227 million, 27 percent less than in the first half of last year.

2020 sales for Calquence, a chronic lymphocytic leukemia treatment, grew to $522 million compared with $164 million in 2019. In the first half of 2021, sales were $490 million. The drug received FDA approval in November 2019.

R&D Progress

Despite the occasional setback, which is to be expected, we also had 14 data or regulatory designations for accelerated, priority or other expedited review in major markets,” Soriot says. “We had remarkable pipeline and regulatory performances in 2020, with 29 approvals of new medicines or life-cycle management indications in major markets.”

In 202o, AstraZeneca spent $5.99 billion on R&D, decreasing 1 percent versus the 2019 period. Reported first-half 2021 R&D expenses were $3.54 billion, 28 percent more than in first-half 2020.

Saphnelo (anifrolumab) was approved by the U.S. Food and Drug Administration during July 2021 for treating moderate-to-severe systemic lupus erythematosus. Saphnelo is a first-in-class type I interferon receptor antibody and the first new medicine in more than a decade for patients with systemic lupus erythematosus.

AstraZeneca announced several pipeline successes in the first half of 2021. One of the most recent approvals, in August, was for Saphnelo in the United States for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.

Saphnelo (anifrolumab-fnia) is a fully human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, blocking the activity of type I IFNs.4 Type I IFNs such as IFN-alpha, IFN-beta and IFN-kappa are cytokines involved in regulating the inflammatory pathways implicated in SLE.

The FDA approval was based on efficacy and safety data from the Saphnelo clinical development program, including two 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 use compared to placebo, with groups receiving standard therapy.

This marks the first regulatory approval for a type I interferon (type I IFN) receptor antagonist and the only new treatment approved for SLE in more than 10 years. Type I IFN plays a central role in the pathophysiology of lupus and increased type I IFN signaling is associated with increased disease activity and severity.

AstraZeneca acquired global rights to Saphnelo through an exclusive license and collaboration agreement with Medarex Inc. in 2004. The option for Medarex to jointly promote the product expired on its acquisition by Bristol Myers Squibb in 2009. Executives say under the agreement, AstraZeneca will pay Bristol Myers Squibb a low-to-mid-teens royalty for sales dependent on geography.

Ultomiris was approved in September in the European Union for expanded use to include children (with a body weight of 10 kg or above) and adolescents with PNH, an ultra-rare and severe blood disorder characterized by the destruction of red blood cells that can cause thrombosis and result in organ damage and potentially premature death.

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

In May, Tagrisso received regulatory approval in the EU for the adjuvant treatment of adult patients with early-stage (IB, II and IIIA) EGFRm NSCLC after complete tumor resection with curative intent. Tagrisso is indicated for EGFRm patients whose tumors have exon 19 deletions or exon 21 (L858R) mutations.

The approval was based on positive results from the ADAURA Phase III trial in which 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. In addition, the trial showed a statistically significant and clinically meaningful improvement in DFS for Tagrisso in the overall trial population, a key secondary endpoint.

In July 2021, Imfinzi received regulatory approval in China for the first-line treatment of adult patients with 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 (NMPA) was based on positive results from the CASPIAN Phase III trial, which showed that Imfinzi plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone.

In May 2021, the company announced positive high-level results from the final analysis of the POSEIDON Phase III trial, which showed the combination of Imfinzi, tremelimumab, and chemotherapy demonstrated a statistically significant and clinically meaningful OS benefit versus chemotherapy alone. This immunotherapy combination also demonstrated a statistically significant improvement in progression-free survival (PFS) versus chemotherapy alone, as previously reported in October 2019. 

In June, Lynparza was granted conditional approval in China to treat adults with germline (inherited) or somatic (spontaneous) BRCAm Stage IV, castration-resistant prostate cancer who have progressed following treatment that included a new hormonal agent (abiraterone, enzalutamide).

The approval by China’s NMPA was based on a subgroup analysis of the PROfound Phase III trial, which showed that Lynparza demonstrated a substantial improvement in radiographic progression-free survival and OS versus abiraterone or enzalutamide in men with BRCA1/2 mutations. Continued approval is contingent upon verification and description of clinical benefit in a planned bridging trial with Chinese patients.

In August, Farxiga was approved in Japan for the treatment of chronic kidney disease (CKD) in adults with and without type 2 diabetes. The approval by Japan’s Ministry of Health, Labour and Welfare (MHLW) is based on positive results from the DAPA-CKD Phase III trial. The decision follows the Priority Review designation granted by the MHLW earlier this year. The drug is marketed in Japan as Forxiga.

The drug was also approved in August in the European Union and in April in the United States for the treatment of CKD in adults with and without type 2 diabetes and is under review in several other countries around the world.

Recent notable clinical trial results include August’s announcement of positive high-level results from the FoCus Phase III trial in Wilson disease showing ALXN1840 met the primary endpoint with a statistically significant improvement in daily mean copper mobilization from tissues, demonstrating superiority compared with standard-of-care (SoC) treatments.

The primary endpoint gauged the daily mean Area Under the Effect Curve (AUEC) for directly measured non-ceruloplasmin-bound copper (dNCC) over 48 weeks. This novel measure assesses the daily mean copper mobilized from tissues, reflecting the underlying burden of the copper accumulation.

Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised. Damage from toxic copper build-up in tissues and organs leads to liver disease, psychiatric and/or neurological symptoms. ALXN1840, a potential new once-daily, oral medicine, demonstrated approximately three times greater copper mobilization than SoC.

The company in September announced detailed positive results from the head-to-head DESTINY-Breast03 Phase III trial showing that Enhertu, an HER2-directed antibody drug conjugate (ADC), demonstrated superior PFS versus trastuzumab emtansine (T-DM1), a HER2-directed ADC approved to treat patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The drug is being by AstraZeneca and Daiichi Sankyo Co. 

Also in September, the company announced positive results from the POSEIDON Phase III trial showing Imfinzi and tremelimumab, when added to platinum-based chemotherapy, demonstrated a statistically significant and clinically meaningful improvement in OS and PFS compared to chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).

According to Susan Galbraith, executive VP, Oncology R&D, “The POSEIDON data offer patients further benefit from Imfinzi and are an important validation of our development strategy to explore novel combinations. Adding a short course of tremelimumab to Imfinzi for those patients already receiving chemotherapy, reduced the risk of cancer progressing or death by 28 percent compared to chemotherapy alone. The results also showed the significant survival improvement did not compromise tolerability in the 1st-line treatment of patients with metastatic non-small cell lung cancer. We look forward to discussing these data with regulatory authorities.”

Dr. Galbraith was appointed to her post in June, following the passing of José Baselga earlier this year. She is on the company’s senior executive team and reports to Soriot.

Dr. Galbraith previously led early-stage Oncology R&D, overseeing the successful progression of seven programs into Phase III trials, with four new medicines now approved in countries around the world. Executives say during this time, she played a pivotal role in the evolution of AstraZeneca’s Oncology strategy, supporting pioneering research, embracing cutting-edge technologies and forging successful partnerships to transform productivity and scientific output.

“Susan is an outstanding oncologist with a track record of delivering breakthrough science,” Soriot says. “Over the past decade at AstraZeneca, she has developed new medicines that have transformed care and improved the lives of patients around the world. She is also an exceptional leader who, together with her high-performing team, will continue to rapidly advance our exciting Oncology pipeline and execute the strategy that Susan helped to devise with José Baselga. Susan’s experience, energy, and passion for investing in the next generation of scientists will be invaluable to AstraZeneca’s next chapter of growth.”

Dr. Galbraith joined AstraZeneca in 2010 and led the development of some of the company’s most innovative cancer therapies. 

Before this appointment, Dr. Galbraith was senior VP and head of Research and Early Development, Oncology R&D, and had overseen the progression of seven programs into Phase III clinical studies, with four new medicines now approved around the world: Lynparza; Tagrisso; Orpathys (savolitinib), an oral, potent and highly selective MET TKI approved in China for treating non-small cell lung cancer patients with MET exon 14 skipping alterations; and Koselugo (selumetinib), an inhibitor of mitogen-activated protein kinase approved in pediatric patients with neurofibromatosis type 1 with plexiform neurofibromas.