Merck's Keytruda: A Blockbuster with an Orphan Heart
While the definition of the highest grossing orphan drug is debated, Merck's Keytruda (pembrolizumab) is a leading contender based on its massive sales coupled with numerous orphan designations. As the world's best-selling drug overall, Keytruda's total revenue reached an astonishing $29.48 billion in 2024. This performance highlights a key dynamic in the pharmaceutical industry: drugs initially designated for rare diseases can become commercial titans through expanded indications in larger patient populations.
Keytruda, a PD-1 inhibitor, first received an orphan drug designation in 2014 for specific, rare indications. Today, it is approved for treating over 40 indications across more than a dozen different types of cancer, from non-small cell lung cancer to melanoma. Its success is a prime example of the lucrative potential unlocked by the U.S. Orphan Drug Act (ODA), passed in 1983 to incentivize the development of drugs for rare conditions.
The Paradox of High-Earning Orphan Drugs
The commercial success of drugs like Keytruda has spurred debate over whether the ODA, intended for public health needs, is being exploited for profit. The process involves leveraging initial orphan status and its benefits—such as tax credits and a period of marketing exclusivity—to fund and fast-track research that later expands to broader, more profitable applications. For instance, a 2017 report found that a significant portion of prescriptions for some top-selling orphan-designated drugs, such as Humira and Remicade, were for non-orphan use.
Incentives Driving the Orphan Drug Market
Drug manufacturers are drawn to the orphan drug market due to several key incentives:
- Market Exclusivity: Companies receive seven years of marketing exclusivity in the U.S. for an orphan indication, effectively shielding them from competition.
- Financial Benefits: Tax credits of up to 50% for qualified clinical trial expenses and waivers for certain FDA application fees significantly reduce development costs.
- Accelerated Pathway: The designation can lead to assistance and faster regulatory reviews from the FDA, bringing products to market more quickly.
- Premium Pricing: The smaller patient population often justifies a high per-patient treatment cost, leading to substantial profits even with limited sales volume.
Comparison of Top-Selling Orphan-Designated Drugs
While Keytruda leads in overall sales, other drugs with orphan designations also generate significant revenue. The table below compares Keytruda with some of the other high-grossing orphan-designated medications, based on recent data and projections.
| Drug (Company) | Primary Therapeutic Area | Key Indications (Orphan/Non-Orphan) | Reported 2024 Sales | Projected 2030 Sales (Orphan-Designated) |
|---|---|---|---|---|
| Keytruda (Merck) | Immuno-Oncology | Melanoma, NSCLC, Head and Neck Cancer, various other cancers (multiple orphan designations) | ~$29.5 Billion | N/A (Projected decline due to patent expiry) |
| Darzalex (Janssen/J&J) | Hematology | Multiple Myeloma, AL Amyloidosis (Orphan-designated) | ~$11.67 Billion | ~$16 Billion |
| Trikafta (Vertex) | Cystic Fibrosis | Cystic Fibrosis (Orphan-designated) | ~$7.68 Billion (2022) | N/A (Continues strong sales) |
| Revlimid (Bristol Myers Squibb) | Hematology | Multiple Myeloma, Myelodysplastic Syndromes (Orphan-designated) | ~$9 Billion (2022) | N/A (Sales impacted by generic entry) |
Market Dynamics and Future Trends
The orphan drug market is dynamic, with oncology treatments being a dominant segment due to the large number of rare cancer subtypes. The high cost of treatment and potential for significant revenue attract major pharmaceutical players and a growing number of specialized firms. However, the market is not without its challenges. The high prices of some orphan therapies, like Zolgensma for spinal muscular atrophy at over $2 million, spark public debate and scrutiny.
Looking ahead, the landscape will continue to shift. While Keytruda faces looming patent expirations around 2028, analysts predict new leaders will emerge. According to one projection, Johnson & Johnson's Darzalex is expected to become the top-selling orphan drug by 2030, driven by its success in treating multiple myeloma. The market is also seeing rapid growth in new modalities like gene and RNA-based therapies, which often target specific, rare conditions. The increasing focus on personalized and precision medicine further fuels the growth of the orphan drug sector, promising a continuous stream of innovative, albeit costly, treatments for rare diseases.
Conclusion
While many drugs have received orphan designations, the title of "highest grossing" is a moving target, often belonging to a product that successfully transitions into a blockbuster treatment for broader applications. Merck's Keytruda is a prime example, dominating overall sales figures in recent years despite its initial orphan status. However, market dynamics and pending patent expirations suggest new leaders, such as Darzalex, are on the horizon. The ongoing evolution of the orphan drug market, driven by powerful incentives and rapid innovation, underscores a future where therapies for rare diseases will continue to have a disproportionate impact on pharmaceutical revenue.
For more information on the incentives and regulations governing the orphan drug market, see the FDA's guidance on the Orphan Drug Act.
