2000–2006

In 2002, its drug Iressa (gefitinib) was approved in Japan as monotherapy for non-small cell lung cancer.^[15] On 3 January 2004 Dr Robert Nolan, a former director of AstraZeneca, formed the management team of ZI Medical.^[16]

In 2005, the company acquired KuDOS Pharmaceuticals, a UK biotech company, for £120 million.^[17] and entered into an anti-cancer collaboration agreement with Astex^[18] It also announced that it had become a Diamond Member of the Pennsylvania Bio commerce organisation.^[19]

In 2006, following a collaborative relationship begun in 2004, AstraZeneca acquired Cambridge Antibody Technology for £702 million.^[20]

2007–2012: The patent cliff and subsequent acquisitions

In February 2007, AstraZeneca agreed to buy Arrow Therapeutics, a company focused on the discovery and development of anti-viral therapies, for US$150 million.^[21] AstraZeneca's pipeline, and "patent cliff", was the subject of much speculation in April 2007 leading to pipeline-boosting collaboration and acquisition activities.^[22] A few days later AstraZeneca acquired US company MedImmune for about US$15.2 billion to gain flu vaccines and an anti-viral treatment for infants;^[23] AstraZeneca subsequently consolidated all of its biologics operations into a dedicated biologics division called MedImmune.^[24]

In 2010, AstraZeneca acquired Novexel Corp, an antibiotics discovery company formed in 2004 as a spin-off of the Sanofi-Aventis anti-infectives division. Astra acquired the experimental antibiotic NXL-104 (CEF104) (CAZ-AVI) through this acquisition.^[25][26]

In 2011, AstraZeneca acquired Guangdong BeiKang Pharmaceutical Company, a Chinese generics business.^[27]

In February 2012, AstraZeneca and Amgen announced a collaboration on treatments for inflammatory diseases.^[28] Then in April 2012, AstraZeneca acquired Ardea Biosciences, another biotechnology company, for $1.26 billion.^[29] In June 2012, AstraZeneca and Bristol Myers Squibb announced a two-stage deal for the joint acquisition of the biotechnology company Amylin Pharmaceuticals.^[30][31] It was agreed that Bristol Myers Squibb would acquire Amylin for $5.3 billion in cash and the assumption of $1.7 billion in debt, with AstraZeneca then paying $3.4 billion in cash to Bristol Myers Squibb, and Amylin being folded into an existing diabetes joint venture between AstraZeneca and Bristol Myers Squibb.^[31]

2013 restructuring and beyond

The road to authorisation by the European Medicines Agency

In March 2020, the company announced that it would be donating PPE, including 9 million face masks, to help support various international health organisations mitigating the COVID-19 pandemic.^[99]

In April 2020, Chief Executive Pascal Soriot, reported that the company was working with GlaxoSmithKline and the University of Cambridge to develop a new laboratory capable of conducting 30,000 COVID-19 tests per day.^[100] The company also announced plans for a clinical trial to assess the potential use of Calquence in the treatment of COVID-19.^[101]

In June 2020, the National Institute of Allergy and Infectious Diseases (NIAID) confirmed that the third phase of testing for potential vaccines developed by Oxford University and AstraZeneca would begin in July 2020.^[102] One of them, AZD1222, reached phase III trials.^[103]

On 23 November 2020, Oxford–AstraZeneca announced the vaccine's successful trial, preventing 70% of people developing symptoms.^[104] The researchers thought that the figure might be as high as 90% if they tweaked the dose.^[105]

In January 2021, India approved the use of the Oxford–AstraZeneca vaccine, paving the way for a mass immunisation campaign in the world's second most populous country. It was announced that the Oxford–AstraZeneca shot would be made locally by the Serum Institute of India (SII) with a brand name COVISHIELD.^[106]

Side-effects

On 29 January 2021, the European Medicines Agency (EMA) recommended granting a conditional marketing authorisation for AZD1222 in people from 18 years of age.^[107] By mid-March 2021, The Netherlands, Denmark, Norway, Iceland, Bulgaria and Ireland had suspended the use of the AstraZeneca vaccine due to worries over six cases of a "rare combination" of blood clots with lowered blood platelets, see embolic and thrombotic events after COVID-19 vaccination. The temporary halt was against the advice of the European Union's medicines regulator who said the benefits of the vaccine still outweigh any potential risks.^[108]

EMA issued a statement on 18 March 2021 stating that no association between vaccination with AstraZeneca vaccines and clot-related cases had been found, but this could not be ruled out and further investigations were being carried out. The EMA also stressed that the benefits of AstraZeneca vaccine outweigh the risks of possible side effects.^[109]

Name change

On 30 March 2021, the Swedish Medicines Agency, Läkemedelsverket, announced that following the prior approval of the EMA^[110] it would change the name of the vaccine to Vaxzevria, stressing that only the name of the vaccine would change, not the composition.^[111][112]

Side-effects

On 6 April 2021, EMA head of vaccines Marco Cavaleri announced that it could be declared that there was a link between the Oxford–AstraZeneca COVID-19 (Vaxzevria) vaccine and rare blood clots associated with low platelet counts.^[113][114] In a statement the following day, the EMA confirmed the link, but continued to recommend the vaccine, saying the benefits of the vaccine far outweigh the risks.^[115][116] Later, a Scottish vaccine efficacy study confirmed the validity of this statement, showing an 88 percent reduction in the risk of hospitalization after the first dose of Vaxzevria from the fourth week onwards.^[117] The European Medicines Agency also identified, over time, the development of the rare neurological disease Guillain-Barré syndrome (GBS) as a possible side effect of Vaxzevria. By the time of the EMA's decision in September 2021, Guillain-Barré syndrome was unlikely to have occurred, with only 833 cases of GBS reported in 8 months following the administration of 592 million doses of the vaccine.^[118] In December 2021, the scientists from Arizona State University and Cardiff University identified “the trigger” behind blood clots. Professor Alan Parker said: “Our data confirms PF4 can bind to adenoviruses, an important step in unravelling the mechanism underlying VITT.^{[lower-alpha 1]} Establishing a mechanism could help to prevent and treat this disorder.”^[119][120]

Lawsuits

In April 2021, the European Commission announced that it would sue Astra Zeneca for delaying the timely delivery of Vaxzevria at a time when "every vaccine counts, because every vaccine can save lives".^[121][122] In September 2021, the lawsuit was finally settled with AstraZeneca agreeing to deliver 60 million doses of vaccines to EU member states by October, 75 million by the end of the year, and 65 million more by April 2022.^[123]

Political lobbying

AstraZeneca is a member of the Personalized Medicine Coalition, a medical research advocacy group that lobbies on behalf of the pharmaceutical industry.^[136]

Following 2008 Sichuan earthquake

AstraZeneca's reputation in China was tarnished following the failure of its Chinese subsidiary to timely donate to relief efforts following the 2008 Sichuan earthquake.^[137]: 121 Typically, donations for disaster relief in China are made through funds established through the Chinese Ministry of Civil Affairs and its subordinate organization the Red Cross Society of China.^[137]: 121 AstraZeneca had a corporate rule prohibiting foreign subsidiaries from making donations to local governments and the company construed this rule as prohibiting donations for Sichuan earthquake relief efforts.^[137]: 121 AstraZeneca's Chinese subsidiary received major backlash for its failure to donate.^[137]: 121 While corporate approval was ultimately given for the Chinese subsidiary to donate, the approval came after long delay.^[137]: 121

Seroquel

In April 2010, AstraZeneca settled a qui tam lawsuit brought by Stefan P. Kruszewski for US$520 million to settle allegations that the company defrauded Medicare, Medicaid, and other government-funded health care programs in connection with its marketing and promotional practices for the blockbuster atypical antipsychotic, Seroquel. According to the settlement agreement, AstraZeneca targeted its illegal marketing of the anti-psychotic Seroquel towards doctors who do not typically treat schizophrenia or bipolar disorder, such as physicians who treat the elderly, primary care physicians, pediatric and adolescent physicians, and in long-term care facilities and prisons.^[138]

In March 2011, AstraZeneca settled a lawsuit in the United States totalling US$68.5 million to be divided up to 38 states.^[139]

Nexium

The company's most commercially successful medication is esomeprazole (Nexium). The primary uses are treatment of gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by Helicobacter pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohn's disease. When it is manufactured the result is a mixture of two mirror-imaged molecules, R and S. Two years before the omeprazole patent expired, AstraZeneca patented S-omeprazole in pure form, pointing out that since some people metabolise R-omeprazole slowly, pure S-omeprazole treatment would give higher dose efficiency and less variation between individuals.^[140] In March 2001, the company began to market Nexium, as it would a brand new drug.^[141]

The (R)-enantiomer of omeprazole is metabolized exclusively by the enzyme CYP2C19, which is expressed in very low amounts by 3% of the population. Treated with a normal dose of the enantiomeric mixture, these persons will experience blood levels five-times higher than those with normal CYP2C19 production. In contrast, esomeprazole is metabolized by both CYP2C19 and CYP3A4, providing less-variable drug exposure.^[142] While omeprazole is approved only at doses of up to 20 mg for the treatment of gastroesophageal reflux,^[143] esomeprazole is approved for doses up to 40 mg.^[144]

In 2007, Marcia Angell, former editor-in-chief of the New England Journal of Medicine and a lecturer in social medicine at the Harvard Medical School, said in Stern, a German-language weekly newsmagazine, that AstraZeneca's scientists had misrepresented their research on the drug's efficiency, saying: "Instead of using presumably comparable doses [of each drug], the company's scientists used Nexium in higher dosages. They compared 20 and 40 mg Nexium with 20 mg Prilosec. With the cards having been marked in that way, Nexium looked like an improvement – which however was only small and shown in only two of the three studies."^[145]

Bildman fraud, sexual harassment and faithless servant clawback

On 4 February 1998, Astra USA sued Lars Bildman, its former president and chief executive officer, seeking US$15 million for defrauding the company.^[146] The sum included US$2.3 million in company funds he allegedly used to fix up three of his homes, plus money the company paid as the result of the EEOC investigation. Astra's lawsuit alleged Bildman sexually harassed and intimidated employees, used company funds for yachts and prostitutes, destroyed documents and records, and concocted: "tales of conspiracy involving ex-KGB agents and competitors. This was in a last-ditch effort to distract attention from the real wrongdoer, Bildman himself." Bildman had already pleaded guilty in US District Court for failing to report more than US$1 million in income on his tax returns.^[147] In addition, several female co-workers filed personal sexual-harassment lawsuits against Bildman.^[148] In April 1998, Bildman was sentenced to 21 months in prison three months after he pled guilty to filing false Federal tax returns.^[149][147]

In February 1998, AstraZenaca's U.S. affiliate Astra U.S.A. agreed to a $10 million settlement after an Equal Employment Opportunity Commission investigation which started in May 1996 found that sexual harassment against female employees.^[150] 120 former female employees of Astra were interviewed during the inquiry, with about 80 of them being identified as able to file claims.^[150] Astra U.S.A. also issued a statement of apology for the hostile work environment.^[150]

In Astra USA v. Bildman, 914 N.E.2d 36 (Mass. 2009), applying New York's faithless servant doctrine, the court held that a company's employee who had engaged in financial misdeeds and sexual harassment must "forfeit all of his salary and bonuses for the period of disloyalty".^[151] The court held that this was the case even if the employee "otherwise performed valuable services", and that the employee was not entitled to recover restitution for the value of those other services.^[151][152] The decision attracted a good deal of attention by legal commentators.^[153]

CAFÉ study

In 2004, University of Minnesota research participant Dan Markingson took his own life while enrolled in an industry-sponsored pharmaceutical trial comparing three FDA-approved atypical antipsychotics: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone). University of Minnesota Professor of Bioethics Carl Elliott noted that Markingson was enrolled in the study against the wishes of his mother, Mary Weiss, and that he was forced to choose between enrolling in the study or being involuntarily committed to a state mental institution.^[154] A 2005 FDA investigation cleared the university. Nonetheless, controversy around the case has continued. A Mother Jones article^[154] resulted in a group of university faculty members sending a public letter to the university Board of Regents urging an external investigation into Markingson's death.^[155]

Transfer mispricing

In 2010, AstraZeneca agreed to pay £505 million to settle a UK tax dispute related to transfer mispricing.^[156]

Conflicting commitments to the UK and the EU

In August 2020 AstraZeneca declared towards the European Commission and the EU member states:

"13.1. AstraZeneca represents, warrants and covenants to the Commission and the Participating Member States that: [...] (e) it is not under any obligation, contractual or otherwise, to any Person or third party in respect of the Initial Europe Doses or that conflicts with or is inconsistent in any material respect with the terms of this Agreement or would impede the complete fulfilment of its obligation under this Agreement;"^[157]

However, the UK Secretary of State for Health and Social Care, Matt Hancock, declared in March 2021 that the United Kingdom had been given "exclusivity" and that the EU's treaty was "inferior".^[158][159] After placing the order for AstraZeneca's vaccine, the European Commission mistakenly assumed that it had enough vaccines and initially ordered only 200 million doses from Pfizer–BioNTech when the manufacturers offered 500 million doses to the EU in November 2020.^[160]

However, the contract that AstraZeneca reached with the UK was very similar to that it reached with the EU, and it also contained the phrase "best reasonable efforts"; the UK contract was signed on 28 August 2020, a day after the contract with the EU.^[161] The key difference seems to be that AstraZeneca entered into a preliminary agreement with the U.K. back in May 2020 which arranged for "the development of a dedicated supply chain for the U.K."^[162] The failure to produce the vaccine in the anticipated quantities contributed to the low vaccination rates of vulnerable populations of the European Union at the beginning of the outbreak of more virulent variants of SARS-CoV-2 in early 2021.^[163]

China comments

In May 2023, AstraZeneca's China president said that the company aims to be a "patriotic" company in China that "loves the Communist Party."^[164]