Where are we?

In 2023, the pharmaceutical market saw several products leading in revenues, dominated by treatments for cancer, diabetes, and immunological conditions. The clear top-selling drug was Keytruda (pembrolizumab) from Merck, generating approximately $25 billion in revenue. Keytruda is an immunotherapy used to treat various cancers, including melanoma, lung cancer, and head and neck cancer.

Another significant product was Ozempic (semaglutide) by Novo Nordisk, which had a strong performance treating type 2 diabetes and obesity, reflecting the growing demand for metabolic therapies. This drug saw sales of around $15.4 billion [Best-selling pharmaceuticals of 2023: Metabolic drugs shine].

Humira (adalimumab) by AbbVie, despite facing competition from biosimilars, continued to perform well, bringing in about $14.2 billion. It is used to treat a range of autoimmune conditions like rheumatoid arthritis and Crohn's disease [Top companies and drugs by sales in 2023] [Pharma giants in 2023: Revenue insights by top product categories].

Other notable drugs included Eliquis (apixaban) from Bristol-Myers Squibb and Pfizer, with sales of about $11.5 billion. Eliquis is an anticoagulant used to prevent blood clots in patients with atrial fibrillation and those at risk of stroke.

Additionally, Dupixent (dupilumab) from Sanofi, used for conditions like eczema and asthma, and Skyrizi (risankizumab-rzaa) from AbbVie, for psoriasis and Crohn's disease, were among the top earners, showcasing significant growth in their respective markets.

These figures reflect a continuing trend in the pharmaceutical industry towards specialty medications, particularly those treating chronic and complex conditions.

Is Keytruda’s $25bn unprecedented?

Several drugs have surpassed $25 billion in annual sales. Here are some notable examples:

1. Humira (adalimumab) by AbbVie:

- Humira has consistently been one of the top-selling drugs globally for several years. In 2022, it generated sales of approximately $21.2 billion, and in previous years, it has exceeded $20 billion annually. Although exact figures for 2023 may vary slightly by source, it continued to be a high-revenue product even as it faced biosimilar competition.

2. Keytruda (pembrolizumab) by Merck:

- In 2023, Keytruda set a new record with sales exceeding $25 billion, driven by its broad application in treating various cancers. This made it the highest-grossing pharmaceutical product last year.

3. Comirnaty (Pfizer-BioNTech COVID-19 vaccine):

- In 2021, Pfizer's COVID-19 vaccine Comirnaty generated approximately $37 billion in sales. This exceptional figure was due to the global demand for COVID-19 vaccinations amid the pandemic.

4. Spikevax (Moderna COVID-19 vaccine):

- Moderna’s COVID-19 vaccine, Spikevax, also saw unprecedented sales during the pandemic. In 2021, it brought in around $18.5 billion, and although it did not surpass $25 billion in a single year, it was among the highest annual revenues ever recorded for a pharmaceutical product.

Where did Humira come from?

Humira (adalimumab) has achieved extraordinary cumulative sales since its launch. As of early 2024, the drug has generated over $240 billion in total revenue. This makes Humira one of the best-selling pharmaceuticals of all time.

- Launch Year: 2003

- Cumulative Sales by 2023: Approximately $214.2 billion.

- Projected Cumulative Sales by 2024: Expected to exceed $240 billion.

Humira’s success has been driven by its use in treating a variety of autoimmune conditions and its dominance in the market despite the introduction of biosimilars.

Origins and Launch of Humira (adalimumab)

Humira (adalimumab) is a monoclonal antibody used to treat various autoimmune conditions.

Development:

1. Concept and Research:

- The concept behind Humira dates back to the early 1990s. Researchers aimed to create a fully human monoclonal antibody that could target and neutralize tumor necrosis factor-alpha (TNF-α), a cytokine involved in systemic inflammation.

- TNF-α is implicated in several autoimmune diseases, including rheumatoid arthritis, Crohn's disease, and psoriasis.

2. Biotechnology and Collaboration:

- The biotechnology firm Cambridge Antibody Technology (CAT), based in the UK, played a crucial role in developing the phage display technology used to create fully human monoclonal antibodies.

- Collaboration with BASF Bioresearch Corporation (later acquired by Abbott Laboratories) was instrumental in advancing the research and development of Humira.

Clinical Trials and FDA Approval:

1. Clinical Trials:

- Extensive clinical trials were conducted in the late 1990s and early 2000s to evaluate the safety and efficacy of adalimumab in treating rheumatoid arthritis.

- Trials demonstrated significant improvements in patients’ symptoms, leading to robust evidence supporting its use.

2. FDA Approval:

- Humira received FDA approval on December 31, 2002, for the treatment of rheumatoid arthritis. This approval marked it as the first fully human monoclonal antibody approved by the FDA.

- Subsequent approvals followed for other conditions such as Crohn's disease, ulcerative colitis, psoriasis, and ankylosing spondylitis, based on further clinical trials.

Launch and Market Introduction:

1. Branding and Marketing:

- Abbott Laboratories (now AbbVie, following a spinoff in 2013) launched Humira with a strong marketing campaign highlighting its efficacy and safety profile.

- The name "Humira" stands for "Human Monoclonal Antibody in Rheumatoid Arthritis," reflecting its targeted mechanism of action and primary initial indication.

2. Adoption and Growth:

- The launch was successful due to the significant unmet need for effective treatments for rheumatoid arthritis and other autoimmune conditions.

- Humira’s efficacy, coupled with aggressive marketing and educational campaigns, led to rapid adoption by healthcare providers.

Post-Launch Success and Expansion:

1. Global Expansion:

- Humira quickly expanded its reach globally, gaining approvals in Europe, Japan, and other major markets.

- Its use was expanded to a broad range of autoimmune diseases, significantly increasing its market potential.

2. Sales Milestones:

- By the mid-2000s, Humira was generating billions in annual sales, eventually becoming the world’s top-selling drug.

- AbbVie continued to invest in clinical trials and post-marketing studies, which helped maintain its market leadership despite competition from other biologics and biosimilars.

Was all of this because it was first in class?

No, Humira was not the first drug in its class. It belongs to a class of drugs known as TNF inhibitors, which target and neutralize tumor necrosis factor-alpha (TNF-α), a cytokine involved in systemic inflammation.

Predecessors to Humira:

1. Infliximab (Remicade):

- Approval Year: 1998

- Manufacturer: Initially developed by Centocor (now part of Johnson & Johnson).

- Details: Remicade was the first monoclonal antibody to target TNF-α. It is a chimeric (mouse-human) antibody and was initially approved for the treatment of Crohn's disease and later for rheumatoid arthritis and other autoimmune conditions.

2. Etanercept (Enbrel):

- Approval Year: 1998

- Manufacturer: Developed by Immunex (now part of Amgen and Pfizer).

- Details: Enbrel is a fusion protein that combines the TNF receptor with the Fc portion of the human IgG1 antibody, effectively acting as a TNF inhibitor. It was approved for treating rheumatoid arthritis, psoriatic arthritis, and other inflammatory conditions.

Humira’s Unique Position:

While Humira was not the first TNF inhibitor, it was the **first fully human monoclonal antibody** against TNF-α. This distinction provided several advantages:

- Reduced Immunogenicity: As a fully human antibody, Humira was expected to have a lower risk of inducing an immune response against the drug itself compared to chimeric or fusion proteins.

- Broad Indication Spectrum: Humira was approved for a wide range of autoimmune diseases, expanding its utility and market reach.

Humira’s Launch and Competitive Landscape:

When Humira was launched in 2003, it entered a competitive market with established TNF inhibitors like Remicade and Enbrel. However, its fully human composition and the extensive clinical evidence supporting its efficacy across multiple indications helped it gain a strong foothold and eventually become the best-selling drug globally.

Summary:

Although Humira was not the first TNF inhibitor, its development as the first fully human monoclonal antibody targeting TNF-α provided significant clinical and commercial advantages. This innovation, along with its broad therapeutic applications, contributed to its unprecedented success in the pharmaceutical market.

**Humira (adalimumab)** has generated approximately **$240 billion** in total revenue since its launch. Here's a more detailed breakdown of its sales trajectory over its life cycle:

Sales Milestones:

1. Early Years (2003-2010):

- Launched in 2003, Humira quickly gained traction in the market for rheumatoid arthritis and other autoimmune diseases.

- By 2010, annual sales had reached around $6.5 billion.

2. Growth Period (2011-2015):

- Humira's sales continued to grow significantly, driven by new indications and expanding global markets.

- By 2015, annual sales had surpassed $14 billion, making it the top-selling drug worldwide.

3. Peak Sales (2016-2020):

- Humira maintained its leading position with sales peaking around $19.9 billion in 2018.

- During these peak years, Humira consistently generated annual revenues in the range of $18-$20 billion.

4. Recent Years (2021-2023):

- Despite facing competition from biosimilars, Humira remained a major revenue generator for AbbVie.

- Annual sales slightly declined but still remained robust, contributing around $21.2 billion in 2022.

- Total cumulative revenue by early 2024 is estimated to be approximately $240 billion.

Factors Contributing to Sales:

- Broad Indications: Approved for numerous autoimmune conditions, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and psoriasis.

- Global Reach: Available in more than 60 countries, with significant sales in the U.S., Europe, and emerging markets.

- Strong Marketing: Aggressive marketing and educational campaigns by AbbVie helped maintain its market dominance.

- Continued Research: Ongoing clinical trials and post-marketing studies supported expanded uses and long-term safety data.

Summary:

Humira’s ability to generate around $240 billion in cumulative revenue is a testament to its effectiveness, broad therapeutic applications, and strategic market positioning by AbbVie. It stands as one of the most successful drugs in pharmaceutical history.

Who’s second to Humira?

The drug second to Humira in cumulative revenues is Lipitor (atorvastatin) by Pfizer. Since its launch in 1997, Lipitor has accumulated approximately $160 billion in total sales.

- Launch Year: 1997

- Peak Annual Sales: Lipitor’s peak sales year was 2006, when it generated over $13 billion.

- Cumulative Sales: By the time it lost patent protection in 2011, Lipitor had reached cumulative sales close to $125 billion. Continuing sales post-patent expiry and generics have pushed its cumulative total to around $160 billion.

Lipitor was the best-selling drug for many years due to its effectiveness in lowering cholesterol and reducing the risk of heart disease, making it a staple in cardiovascular treatment.

If we adjust the Lipitor and Humira revenues in 2024 dollars?

To compare the cumulative revenues of Humira and Lipitor in inflation-adjusted figures, we need to account for the varying values of money over time. Here's a step-by-step approach:

1. Humira's Cumulative Revenues (2003-2024):

- Nominal cumulative revenue: $240 billion.

- Most of its sales occurred from 2003 onwards, with significant increases in the 2010s and 2020s.

2. Lipitor's Cumulative Revenues (1997-2024):

- Nominal cumulative revenue: $160 billion.

- The peak sales years were in the early 2000s, with the highest in 2006.

To make a fair comparison, we'll adjust these revenues to a common year, say 2024, using average annual inflation rates.

Steps for Inflation Adjustment:

1. Identify relevant inflation rates for the years involved.

2. Adjust each year's revenue to 2024 dollars using the cumulative inflation factor.

Calculations:

Using average U.S. inflation rates (approximately 2-3% annually):

1. Humira’s Inflation-Adjusted Cumulative Revenues:

- Adjusting from 2003 to 2024.

- Assuming an average annual inflation rate of 2.5%:

- $240 billion in nominal terms would be roughly $280 billion in 2024 dollars.

2. Lipitor’s Inflation-Adjusted Cumulative Revenues:

- Adjusting from 1997 to 2024.

- Early years (1997-2003) see the most significant inflation impact.

- Assuming an average annual inflation rate of 2.5%:

- $160 billion in nominal terms would be approximately $250 billion in 2024 dollars.

Summary of Inflation-Adjusted Figures:

- Humira: Approximately $280 billion in 2024 dollars.

- Lipitor: Approximately $250 billion in 2024 dollars.

Conclusion:

Even after adjusting for inflation, Humira remains ahead in cumulative revenues compared to Lipitor. However, Lipitor’s inflation-adjusted cumulative revenues still highlight its historical significance as a blockbuster drug.

How does $240 billion compare in the consumer world?

While individual consumer products rarely generate as much as $240 billion in cumulative sales, there are several notable examples of product lines and franchises that have achieved or surpassed this milestone. Here are some examples:

1. iPhone by Apple:

- Cumulative Revenue: The iPhone, since its launch in 2007, has generated well over $1 trillion in sales. It remains one of the most successful consumer electronics products ever.

- Key Points: Continuous innovation, yearly new models, and a loyal customer base have driven its massive sales.

2. PlayStation by Sony:

- Cumulative Revenue: The PlayStation brand, encompassing multiple generations of consoles since its debut in 1994, has generated over $450 billion in sales.

- Key Points: Strong gaming ecosystem, popular exclusive titles, and hardware sales.

3. Toyota Corolla:

- Cumulative Revenue: The Toyota Corolla, the best-selling car model in history, has sold over 44 million units since its introduction in 1966. This translates to revenue far exceeding $240 billion.

- Key Points: Reliability, affordability, and global availability.

4. Star Wars Franchise:

- Cumulative Revenue: Including movies, merchandise, and related products, the Star Wars franchise has generated over $70 billion. While not a single product, the combined revenue from the franchise's various elements is significant.

- Key Points: Strong fan base, extensive merchandise, and continuous content production.

5. Harry Potter Franchise:

- Cumulative Revenue: The Harry Potter books, movies, and related merchandise have collectively generated around $30 billion. While not as high as $240 billion, it remains one of the most lucrative franchises.

- Key Points: Best-selling books, blockbuster films, and extensive merchandise.

Conclusion:

Most individual consumer products do not reach $240 billion in cumulative sales. However, product lines and franchises with multiple related products, continuous innovation, and a strong brand presence can achieve or even surpass this milestone.