The pharmaceutical blockbuster model is wobbling. And no single franchise is safe.
While king Keytruda, Merck’s stalwart oncology drug, continues to rule the first half of 2025 with $15.2B in sales (Q1 $7.2B, Q2 $8.0B), its U.S. patent expiry in 2028 the single biggest loss of exclusivity event on the horizon. In the U.S., Medicare price setting begins January 1, 2028, and the compound patent expires Dec 2028, making KEYTRUDA’s loss of exclusivity arguably the largest single LOE by revenue on the near-term horizon. Merck discloses expected EU market exclusivity loss in 2031 following compound patent expiry.
While GLP-1s continued their ascent in H1 2025, investor sentiment has cooled. Lilly’s stock is down 2% year-to-date while Novo Nordisk has fallen 36%. Morgan Stanley’s late-September downgrade of Novo Nordisk cited stagnant U.S. Rx trends and potential price pressure, even as demand remains high.
Beyond GLP-1s, AbbVie’s immunology bet on Skyrizi is paying off: the IL-23 inhibitor posted over 60% growth in both quarters on expanded use in inflammatory bowel disease and ongoing strength in psoriasis.
Based on H1 2025 sales of the top 10 pharmaceutical products. Categories are simplified: “Diabetes” includes GLP-1/GIP drugs for type 2 diabetes; “Obesity” includes GLP-1/GIP weight-loss drugs; “Immunology” consolidates IL-23, IL-4/13, and other immune-targeted therapies; “Oncology” includes PD-1 and other cancer treatments.
Another piece of context: COVID vaccines topped sales in 2021–22, cementing Pfizer’s status as the top pharma company, temporarily. But by mid-2025 Comirnaty has faded to weak blockbuster status: still above $1B annually but far from the top tier. Pfizer reported 95% operational growth for Comirnaty in Q2, but off a much smaller base than the pandemic peak. Pfizer now trails Merck & Co. in terms of overall revenue.
The pattern: blockbusters now cycle faster: shorter dominance windows, steeper cliffs, quicker replacements. Companies that rode one drug for a decade (think Lipitor, Humira) can’t do that anymore. The new reality: survival depends on building the next franchise before the current one craters. AbbVie executed early, pivoting from Humira to Skyrizi and Rinvoq. Merck is prepping subcutaneous Keytruda ahead of 2028. Lilly and Novo are fighting to sustain GLP-1 pricing and growth. By 2028, today’s top ten will look very different.
| Drug | Manufacturer | Indication | H1 2025 Sales (M USD) | Notes |
|---|---|---|---|---|
| Keytruda | Merck | Oncology (PD-1) | 15161.0 | |
| Ozempic | Novo Nordisk | GLP-1 (T2D) | 9456.0 | H1 total of DKK 64.5B. |
| Mounjaro | Eli Lilly | GLP-1 (T2D) | 9041.0 | |
| Dupixent | Sanofi/Regeneron | Immunology (IL-4/13) | 8026.0 | H1 sales align with Sanofi’s global figure of €7.31B. Regeneron records collaboration revenue / profit share from Sanofi (not a second set of product sales). |
| Skyrizi | AbbVie | Immunology (IL-23) | 7848.0 | |
| Eliquis | BMS/Pfizer | Anticoagulant | 7245.0 | H1 sales reflect BMS’s reported global figure of $7.245B. BMS books global net product sales of Eliquis. Pfizer books “alliance revenues” (its share of the economics), not a second set of product sales. |
| Darzalex | J&J | Oncology (Myeloma) | 6776.0 | |
| Zepbound | Eli Lilly | GLP-1 (Obesity) | 5693.0 | |
| Wegovy | Novo Nordisk | GLP-1 (Obesity) | 5421.0 | H1 total of DKK 36.9B ($5.42B). |
| Opdivo | BMS | Oncology (PD-1) | 4825.0 | |
| Jardiance | Lilly/Boehringer | SGLT2 (T2D/HF) | 4702.0 | H1 sales reflect Boehringer Ingelheim’s global figure of €4.3B ($4.7B). Boehringer Ingelheim reports global net sales for Jardiance. Lilly generally reports royalties/profit-share related to the drug. |
| Entresto | Novartis | Cardiovascular | 4618.0 | |
| Farxiga/Forxiga | AstraZeneca | SGLT2 (T2D/HF) | 4209.0 | |
| Ocrevus | Roche | Neurology (MS) | 3900.0 | H1 sales of CHF 3.506B confirmed. USD value updated to $3.9B to reflect a more accurate H1 2025 CHF-to-USD conversion rate. |
| Rinvoq | AbbVie | Immunology (JAK) | 3746.0 | |
| Tagrisso | AstraZeneca | Oncology (NSCLC) | 3489.0 | |
| Stelara | J&J | Immunology (IL-12/23) | 3278.0 | Steep YoY decline due to biosimilar entry |
| Cosentyx | Novartis | Immunology (IL-17) | 3163.0 | |
| Prevnar | Pfizer | Vaccine | 3043.0 | Represents the combined ‘Prevnar family’ as reported by Pfizer. |
| Verzenio | Eli Lilly | Oncology (CDK4/6) | 2648.0 | |
| Gardasil | Merck | Vaccine (HPV) | 2453.0 | |
| Shingrix | GSK | Vaccine | 2336.0 | H1 sales of £1.72B (~$2.3B). |
| Humira | AbbVie | Immunology (TNF) | 2301.0 | Significant YoY decline due to biosimilar competition confirmed as accurate. |
| Vabysmo | Roche | Ophthalmology | 2250.0 | H1 sales of CHF 2.067B confirmed. USD updated to ~$2.25B reflecting H1 CHF-to-USD conversion. |
| Tremfya | J&J | Immunology (IL-23) | 2142.0 | Q1, Q2, and H1 sales and growth rates confirmed per J&J product-level disclosures. |
Filed Under: Biologics, Dermatology, Immunology, Infectious Disease, Metabolic disease/endicrinology, Oncology
