COVID-19 has not only changed the global healthcare landscape, but also the old world order for drug developers. In 2021, governments and healthcare systems spent US$36.9 billion on Pfizer’s COVID-19 vaccine Comirnaty (tozinameran), making it the best-selling drug of the year and catapulting Pfizer to the top of the biggest companies list (Fig. 1). A predicted further $33.6 billion of Comirnaty sales this year will help Pfizer remain the biggest pharma company by sales and Comirnaty 2022’s biggest drug. The sheer pace of Comirnaty’s growth since launch means it has become the fastest-selling drug in pharma history. Pfizer’s dominance should be further cemented in 2022 by expected sales of the COVID-19 antiviral Paxlovid (nirmatrelvir and ritonavir), which Pfizer guided could sell $22 billion this year.

Fig. 1 | Top companies and drugs by sales in 2021. a | Top ten companies by sales of prescription and over-the-counter drugs. b | Top ten drugs by sales globally. Source: EvaluatePharma.

While Pfizer has created a gap of over $16 billion between it and nearest rival AbbVie in 2021, sales of Comirnaty and other vaccines are expected to fall sharply in the coming years. Most western countries have now double, if not triple, vaccinated their citizens, and less virulent strains of SARS-CoV-2 are lessening the need for fourth vaccinations for now.

Despite no COVID-19-related products AbbVie rose by one to its second-place spot in 2021, thanks to cash cow Humira (adalimumab), the continued success of the BTK inhibitor Imbruvica (ibrutinib) for blood cancers and sales of psoriasis treatment Skyrizi (risankizumab) rising by 85% in 2021. However, the company will start slipping down the rankings, as biosimilars of Humira enter the market in 2023.

The gains seen by Pfizer and AbbVie have been to the detriment of Novartis and Roche, which dropped two and three places down the rankings since 2020, respectively. Neither company has COVID-19-related products, and the pandemic has resulted in lower-than-expected sales of Ocrevus (ocrelizumab), Roche’s biggest product, due to fears around its immunosuppressive effects. Roche is also still feeling the effects of the biosimilar erosion of some of its biggest products such as Avastin (bevacizumab). Novartis, on the other hand, is struggling with a relatively lacklustre pipeline, which might be remedied through acquisitions using the $20.7 billion it received by selling its 33% stake in Roche last year.

In more normal times, Merck & Co. might have moved up the rankings due to continued strong sales of Keytruda (pembrolizumab), the fourth best-selling drug in 2021. Instead, it remains at number seven. However, the PD1 inhibitor could bank $20 billion of sales this year, as it continues one of pharma’s most successful expansion strategies — a strategy that, barring a shift in the expected need for COVID-19 vaccines, could see Keytruda become the biggest-selling drug in 2023, with revenues of $21.6 billion.

AstraZeneca’s entrance into the top ten in 2021 is due to strong growth in oncology and its $39 billion purchase of Alexion last year bringing established blockbusters for several rare diseases. Growth is expected to come from Enhertu (trastuzumab deruxtecan), an antibody–drug conjugate for HER2+ breast cancer that has shown impressive efficacy.

Despite having three of the top 10 best-selling drugs, Bristol Myers Squibb has not advanced up the chart. Furthermore, sales of one of those best sellers, Revlimid (lenalidomide) are expected to dip this year as patents on the multiple myeloma blockbuster start to expire. While Opdivo (nivolumab), Bristol’s biggest product, is unlikely to catch Keytruda, it remains in the top 10, and growing peri-operative use could help it regain some of the ground it has lost to Merck’s checkpoint inhibitor in metastatic cancers.

Strong sales of the HIV combination therapy Biktarvy (bictegravir; emtricitabine; tenofovir alafenamide) are one thing Gilead can count on for a while, but sales of its COVID-19 antiviral Veklury (remdesivir), which contributed $5.6 billion in 2021, are set to plunge. There are concerns about over-reliance though; Biktarvy made up 33% of total sales in 2021. As such, Gilead is facing increasing pressure for the rest of its pipeline to perform, especially as it has spent over $38 billion on acquiring companies such as Immunomedics and Kite Pharma since 2017.

GlaxoSmithKline (GSK) is also no stranger to investor demands. With no drugs in the top 10 and sitting bottom of the top 10 company table, GSK faces a critical year. Delays to its and Sanofi’s COVID-19 vaccine have seen the two companies miss out on the riches Pfizer and Moderna have enjoyed and left Sanofi stagnating in its number eight position. The performance of GSK’s pharma division will be even more closely watched following the spin out of consumer health division Haleon in July.