Introduction: Why Revenue-Loss Drugs Matter
As is the case every year, a handful of highly successful drugs lose their patents. Such pharmaceuticals have been the source of billions of dollars in sales in the annual revenue by the time they reach the end of their life cycle. The instant they lose their exclusivity, the market changes rapidly. There is a dramatic fall in prices, an increase in generic competition, and a reverse in demand for APIs.
For manufacturers of API, generic pharmaceutical firms, CDMOs, exporters, and distributors, these loss-of-revenue drugs provide the largest commercial potential in the drug industry.
This piece of writing focuses on the most profitable drugs that are going to face patent expiry during 2025-2030, together with their API and market potential.
1. What Happens When a Blockbuster Loses Patent Protection?
When a patented drug becomes generic-eligible:
- The originator's revenue declines significantly, usually between 50 and 80% in the first year.
- The generic companies introduce their products at lower prices.
- The demand for APIs increases because there are more producers about to start the production.
- Buyers switch to cheaper options to cut down healthcare costs.
- The competition in the tenders is particularly intense in the United States, Europe, Latin America, Africa, and Southeast Asia.
This scenario creates a time-limited opportunity for the manufacturers to gain a market share.
2. Top Revenue-Losing Drugs After Patent Expiry (2025–2030)
A selection of drugs that will likely lose large amounts of revenue because of the expiration of exclusivity (LOE) and their possible API potential is shown below.
A. Keytruda (Pembrolizumab)
Revenue before LOE: ~$25–30 billion/year
LOE window: 2028
Therapeutic area: Oncology (PD-1 inhibitor)
Type: Biologic (no traditional API)
The reason for loss of revenue:
Huge sales in the Oncology; biosimilars will gradually lose revenue in all parts of the world after 2028.
API / market potential:
- No small-molecule API
- Greatest potential for biosimilar development, collaboration with CDMO and fill–finish
- Huge demand from oncology hospitals and specialty centers
- Attractive for companies with biologics capability
B. Eliquis (Apixaban)
Revenue: ~$12–15 billion/year
LOE window: 2026–2029
Therapy: Anticoagulant
Type: Small molecule
API / market potential:
- One of the most sought-after APIs ahead of 2026
- High-volume demand in tablets/capsules
- Global tenders (cardiology, stroke prevention)
- Strong export opportunity for India & China
- Ideal for manufacturers with robust DMFs
C. Xarelto (Rivaroxaban)
Revenue: ~$8–9 billion/year
LOE window: 2026
Therapy: Anticoagulant
Type: Small molecule
API / market potential:
- Large-volume cardiac API
- Used widely in EU, LATAM, SEA
- Great ROI for early birds
- Good option for raising the generic portfolio
D. Trulicity (Dulaglutide)
Revenue: ~$7–12 billion/year
LOE window: 2027
Therapy Area: Diabetes
Product Type: Biologic (GLP-1 analog)
Market Potential for API:
- There is no classical API since this is a biologic peptide
- The demand for biosimilar products in weight loss and diabetes is increasing rapidly, and thus the need for fill/finish partnerships will increase
- There will be significant growth potential for CDMOs that focus on providing services related to peptides.
E. Imbruvica (Ibrutinib)
Revenue: ~$7–9 billion/year
LOE window: 2028
Therapeutic Area: Hematology/oncology
Product Type: Small molecule
Market potential for API:
- A substantial amount of high-quality oncology APIs are needed and for an ideal ANDA (Abbreviated New Drug Application) for a regulated market
- A product with oncology indications would have the unique opportunity for potentially high-margin generic products
F. Ozempic (Semaglutide)
Revenue: ~$15–20 billion/year (combined with Wegovy)
LOE window: 2028–2029 (varies by region)
Therapeutic Area: Diabetes & Weight Loss
Product Type: Peptide biologic
Market potential for API:
- The commercial interest is enormous
- Firms need to have the capabilities to produce peptide APIs for this compound
- There is considerable global demand for treatment of obesity with high barriers to entry but potentially high margins
G. Eylea (Aflibercept)
Revenue: ~$9–11 billion/year
LOE window: 2025–2026
Therapeutic Area: Ophthalmology (AMD, DME)
Product Type: Biologic
Market potential for API:
- The growing number of biosimilars on the market will likely capture a large market share
- There is increasing demand from hospitals and surgical centers
H. Januvia / Janumet (Sitagliptin)
Revenue: ~$5–7 billion/year
LOE window: 2026
Therapeutic Area: Diabetes
Product Type: Small molecule
Market potential for API:
- The volume of API produced for these products is significantly higher than almost any other therapeutic area due to the significant demand for these products from India, Brazil, Thailand, and the Philippines
- These APIs can be manufactured as generics and marketed to a wide audience
I. Xtandi (Enzalutamide)
Revenue: ~$5–6 billion/year
LOE window: 2026–2027
Therapeutic Area: Oncology
Product Type: Small molecule
Market potential for API:
- Attractive and high-value oncology API
- Priority for generic companies seeking oncology expansion
3. API Market Potential – Molecule by Molecule
Here is a simplified view of API potential for each class:
Small-Molecule APIs (High Opportunity)
- Apixaban
- Rivaroxaban
- Ibrutinib
- Sitagliptin
- Enzalutamide
Why:
- Easier to scale
- Heavy demand from developing markets
- Regulatory filings straightforward
- Excellent export potential
Biologics / Peptide Molecules (Moderate to High Opportunity)
- Pembrolizumab
- Dulaglutide
- Semaglutide
- Aflibercept
Why:
- Very large market sizes
- Fewer competitors
- High-margin opportunity
- Requires strong biotech capability
Generic Formulations (FDF) Opportunity
Big winners in FDF manufacturing:
- Eliquis
- Xarelto
- Sitagliptin
- Ibrutinib
- Enzalutamide
4. Therapeutic Area Opportunities
A. Oncology
Keytruda, Opdivo, Imbruvica, Xtandi
- High value
- Strong hospital-driven demand
- Biosimilars + oncology APIs will dominate
B. Metabolic & Weight Loss
Ozempic, Trulicity, Januvia
- Fastest-growing global market
- High-volume API and peptide demand
C. Cardiology
Eliquis, Xarelto
- Essential therapy area
- Great for high-volume generic production
D. Ophthalmology
Eylea, Lucentis
- Biosimilar uptake increasing
- High cost-saving potential for hospitals
5. How API and Generic strategy effectively benefit Manufacturers
1. Early Start to Drug Master File (DMF) and Regulatory Submission
- Preparation of DMFs should begin 12–24 months prior to being able to market product after expiration
- Profiles should provide the full range of technical support
2. Develop Cost Advantage
- Batch size and process optimization
- COGS must be lowered in order to be competitive during a tender/bid process
3. Partner with CDMOs and Regional Manufacturers
- This is critical for biopharmaceuticals (biologics) and peptide products
- Allows smaller competitors to spread capital outlay over multiple areas
4. Obtain Multi-Region Regulatory Approvals
- US ANDA
- EU DCP
- Explore opportunities in emerging markets such as Brazil, Mexico, Thailand, and South Africa
5. Early Collaboration with Distributors
- Ensure that marketing materials, and hospital outreach are available at the time the patent expires to provide the fastest route to market
- Prepare promotional material and hospital outreach
6. Global Market Impact (US, EU, India, Emerging Markets)
United States
- Most rapid erosion of price; in addition, entered through the first biosimilars and launches of generic products.
Europe
- Major growth has occurred with the increase in the number of biosimilar products and rapid switching to therapeutic equivalents.
India
- A very robust market exists for API exports. There is also a very large internal market for specialty therapies such as diabetes, cardiology and oncology.
Emerging Markets (LATAM, Africa, SEA)
- Generic launches typically occur 2 to 3 years after expiration and can provide a long-term opportunity for sales growth.
7. Risks & Challenges
- Secondary patents and litigation can prolong the launch of biosimilars
- The cost of developing a biosimilar is very high
- Regulatory expectations for injectables/peptides is very high
- There is already significant market saturation with common diabetes and cardiology therapies
