Top 200 medicines report 2023: Keytruda’s reign begins

Top 200 medicines report 2023: Keytruda’s reign begins

By Andrew Humphreys

The Merck & Co. checkpoint inhibitor Keytruda has taken command of the No. 1 position among top-selling pharma products. Keytruda is on track to be the only medicine that will generate more than $20 billion in sales this year. During the first six months of 2023, worldwide sales for the product were reported at about $12.07 billion by Merck, representing a 20 percent year-over-year increase. Excluding the impact of foreign exchange, sales improved 23 percent versus Keytruda’s first-half 2022 performance.

The meteoric rise of Keytruda (pembrolizumab) has transformed Merck into a leading oncology player in the industry. Merck maintains the biopharma arena’s largest immuno-oncology clinical research program.

Merck had 48 approved indications across an oncology portfolio encompassing five brands as of June 2023, with the potential to secure more than 80 oncology approvals ranging from June 2022 through 2028, according to company officials. Keytruda had been approved for 35 uses across 16 types of cancer as of July 2023, the most of any oncology drug, and Merck has anticipated doubling that amount in the years ahead. There are more than 1,600 clinical studies evaluating Keytruda across a broad range of cancers and treatment settings.

An anti-programmed death receptor-1 (PD-1) therapy, Keytruda acts by increasing the ability of the body’s immune system to help detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes that may affect tumor cells and healthy cells.

Evaluate Vantage’s 2023 Preview projected that Keytruda would outsell the medicine’s “nearest rival” Comirnaty by nearly $4 billion during this year. The cancer product is additionally forecast to be 2023’s largest grower, with strong demand anticipated to add $3 billion in new sales this year, according to the Evaluate Vantage report.

Keytruda is poised to begin an annual run as the globe’s top-selling pharmaceutical product, as Evaluate Pharma has projected 2028 worldwide sales of $30.08 billion, with the next closest competitor that year predicted to be Sanofi’s eczema treatment Dupixent (dupilumab) at $18.83 billion. The sales-leading baton has been passed on to the Merck medicine from Comirnaty, which held the top spot during 2022 and 2021 due to the COVID-19 pandemic. During those two years combined, Pfizer reported global revenue of nearly $74.59 billion on account of Comirnaty alone. To put that massive number in perspective, only seven other companies in the industry generated more than that much revenue from their entire prescription product portfolio during that time span.

An mRNA-based coronavirus vaccine to help prevent COVID-19, Comirnaty is being jointly developed and commercialized with BioNTech. The two companies equally share the costs of development for the Comirnaty program.

As expected, Comirnaty total revenue in 2023 is experiencing a significant decline. First-half 2023 Comirnaty revenue reported by Pfizer totaled $4.55 billion, a decrease of about $17.52 billion (78 percent operationally) compared with same-period 2022. This result was largely driven by lower contracted deliveries and demand in international markets, as well as lower U.S. government contracted deliveries with anticipated transition to traditional commercial market sales during the last six months of 2023.

Pfizer’s revenue guidance as of August 2023 for Comirnaty was $13.5 billion for the full year, which would be a 64 percent fallout from the vaccine’s 2022 performance, but that would still represent a higher 2023 total than those projected to be generated by all other pharmaceutical products except for Keytruda and Humira (adalimumab).

Paxlovid became the fourth medicine and the first oral antiviral pill to receive U.S. marketing approval to treat COVID-19 in adults when the Food and Drug Administration gave the green light in May 2023. U.S. regulators cleared Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) for treating mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. Paxlovid was initially made available in the United States during December 2021 under Emergency Use Authorization (EUA).

Unlike Comirnaty, Paxlovid sales increased year-over-year during the first quarter 0f 2023, improving by $2.8 billion to a total of nearly $4.07 billion. This performance was primarily driven by favorable timing of final delivery associated with the U.S. government contract before expected transition to traditional commercial markets during second-half 2023; strong demand in China due to increased COVID-19 infections; and launch in certain international markets. The second quarter was a completely different story though, as Paxlovid sales plummeted 98 percent to $143 million compared to Q2 2022. First-half 2023 revenue amounted to $4.21 billion, down 54 operationally versus the first six months of 2022. Paxlovid revenue of $8 billion was projected for full-year 2023 by Pfizer in August, which would represent a 58 percent decline from the 2022 amount.

Moderna sales from COVID-19 products have also taken a strong downturn in 2023. Moderna reported COVID-19 product sales of almost $17.68 billion in 2021 and nearly $18.44 billion in 2022. On the other hand, the Cambridge, Mass.-based biotech company reported first-half 2023 revenue of about $2.21 billion, well off the pace from the previous two years. But as of August, Moderna was expecting full-year 2023 COVID-19 vaccine sales of $6 billion to $8 billion, dependent on U.S. vaccination rates. Company management said total expected 2023 sales consist of $4 billion from existing Advance Purchase Agreements and $2 billion to $4 billion from additional sales to the U.S., Japan, EU and other countries.

Moderna’s COVID-19 vaccine Spikevax was made available under EUA in the United States on Dec. 18, 2020, the second to be granted that authorization after Pfizer’s vaccine was cleared one week earlier. Moderna’s Omicron-containing bivalent COVID booster candidate mRNA-1273.214 and BA.4/BA.5 Omicron-targeting bivalent COVID-19 booster vaccine mRNA-1273.222 also have garnered EUA from the FDA.

Spikevax put Moderna on the map in terms of having a product generating blockbuster sales, but the company has been on the radar of industry analysts for years as one that will bring to market  promising messenger RNA products.

Moderna is preparing for a potential 2024 commercial launch of the company’s investigational RSV vaccine for older adults. Moderna began a Phase III study in July 2023 of mRNA-4157, the company’s individualized neoantigen therapy in combination with Keytruda, for melanoma. Management anticipates six major vaccine launches from Moderna’s respiratory franchise (COVID-19, RSV, flu, and combinations), with anticipated yearly sales of $8-15 billion by 2027.

That brings us to Humira, which before the ascent of Keytruda and the arrival of the COVID-19 combatants, represented the king of medicines. The AbbVie product succumbed to the loss of U.S. exclusivity in January 2023. As a result, AbbVie’s Humira net revenue for the first six months of 2023 totaled $7.55 billion, down 25.2 percent on a reported basis and 24.6 percent operationally.

The autoimmune drug debuted in the U.S. marketplace during January 2003, and by 2012 Humira had vaulted to the top of the leaderboard in terms of sales among all prescription pharmaceuticals. The fully human anti-TNFα monoclonal antibody would go on to become the top-selling pharma product of all-time. The biologic therapy represents the industry’s first brand to generate $20 billion in annual sales.

Evaluate Vantage projections for 2023 show that three of the top six largest new sales generators among drugs are set to benefit from rising obesity and type 2 diabetes rates: Lilly’s dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist Mounjaro (tirzepatide), and Novo Nordisk’s GLP-1 agonists Wegovy (semaglutide) and Ozempic (semaglutide). Evaluate Pharma has forecast global sales in 2028 of $17.88 billion for Ozempic and $17.17 billion for Mounjaro, which would rank those medicines third and fourth after Keytruda and Dupixent.

View the listing of the top 200 medicines based on global sales during 2022 in the Med Ad News August 2023 digital edition.

Andrew Humphreys is contributing editor of PharmaLive and Med Ad News.