The rare disease field is undergoing a period of great upheaval, caught between a fickle FDA and competition for investor attention from mainstream blockbusters such as obesity drugs. However, despite the “rough waters”, global sales of orphan drugs are expected to increase and exceed $400 billion by 2032, according to Evaluate’s new 2026 Orphan Drug Report.
Rare disease drugs generate a whopping $409 billion in annual revenue, representing more than 21% of global prescription drug sales of approximately $1.9 trillion by 2032, according to a new report released Thursday, March 12. This is up from 15% in 2022.
While the outlook is bullish, the path to $400 billion likely won’t be a straight line. Despite some recent policy successes, such as updating the Inflation Control Act (IRA) exemption and reauthorizing the Pediatric Rare Disease Priority Review Voucher Program, the market remains vulnerable to stringent FDA and potential pricing pressures.
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By 2032, 10 existing treatments are expected to lead the way as best-selling orphan drugs, with eight of these expected to each generate annual sales of more than $6 billion.
Johnson & Johnson is poised to take the orphan drug crown, both as a company and from a product standpoint.
The company’s multiple myeloma treatment Darzalex (daratumumab) is projected to become the best-selling orphan drug with sales of $11.8 billion. Although this is down from the drug’s $14.4 billion in sales in 2025, the market exclusivity for the subcutaneous formulation has increased and the commercial life of the franchise has effectively doubled.
J&J’s position is further strengthened by Carvykti, a multiple myeloma CAR-T treatment in partnership with Legend Biotech, which secures the No. 8 spot with projected sales of $6.3 billion.
Thanks to these drugs, J&J has earned the title of the largest company in sales of orphan drugs, with revenue from this category expected to reach nearly $31 billion in 2032, according to Evaluate.
Vertex is another company with two drugs in the top 10 list. Boston Biotech’s once-daily three-drug combination drug Ariftrec for the treatment of cystic fibrosis has become the world’s second-best-selling orphan drug, with sales expected to reach $9.3 billion by 2032. Meanwhile, the company’s older model, Trikafta, will take last place with sales of $4.9 billion.
Alnylam’s fast-growing transthyretin amyloidosis (ATTR) RNA interference drug Amvuttra (vutriciran) is likely to take third place with sales of $7.5 billion in 2032. The expected loss of market exclusivity for Pfizer’s first-in-class tafamidis has raised some questions about the potential for growth of the drug, and of the ATTR market as a whole.
Perhaps the most dramatic change in the rankings is the rise of argenx. Argenx, known as the “gate-busting” force, is expected to replace Pfizer in the orphan drug sales rankings in 2032, thanks to the successful launch of the autoimmune drug Vibgart (efgartigimod alfa). With estimated total orphan drug sales of $11.2 billion, the Dutch biotech company ranks eighth among companies, ahead of Merck & Co. ($9.9 billion) and Bristol-Myers Squibb ($9.7 billion). Argenx also has the distinction of being the only company on Evaluate’s list whose 2032 revenue came entirely from orphan drugs.
AstraZeneca’s complement inhibitor Ultomiris, Merck’s pulmonary arterial hypertension treatment Winreair, B-One Medicine’s blood cancer treatment Brukinsa and Roche’s hemophilia A treatment Hemlibra top the list of orphan drugs.
Among the 10 companies, Merck has the fastest growth in orphan sales, with a compound annual growth rate of 23% from 2025 to 2032, followed by Argenx at 22%.
In contrast to the increasing share of orphan drugs in the overall pharmaceutical market, the footprint of orphan drugs in the R&D pipeline is beginning to shrink. Valuation analysts expect the share of drug sales for rare disease candidates in development to decline from a projected peak of 30% in 2027 to 22% in 2032.
“This likely reflects increased interest in and investment in big therapeutics for big diseases, including most notably GLP-1-based therapies,” Evaluate analysts noted. With major pharmaceutical companies facing a total patent cliff of $300 billion by the end of 2010, the need to develop drugs for major indications remains high, the researchers added.
Push and pull policies
J&J’s Darzalex and argenx’s Vyvgart are able to protect their hefty sales prospects thanks to recent IRA revisions. Under the original IRA, only drugs with a single orphan indication were excluded from U.S. government price negotiations. As part of President Donald Trump’s One Big Beautiful Bill Act, this provision expanded the orphan exemption to drugs with multiple indications.
In another important industry-friendly amendment, the countdown to eligibility for price reductions under an IRA will not begin until the first non-orphan approval is completed.
But the regulatory environment has become increasingly unpredictable for rare disease drug developers these days, thanks to what Evaluate calls “mixed signals” from the FDA.
Although the FDA has introduced a “plausible mechanistic pathway” to facilitate personalized treatments targeting the genetic abnormalities behind rare diseases, the agency has also rejected several rare disease drugs, sparking an industry-wide outcry.
Notable among these rejections is UniQure’s Huntington’s disease gene therapy candidate, AMT-130. The one-time treatment regimen was shown to reduce Huntington’s disease progression by 75% three years after treatment when compared to external controls.
However, after uniQure announced in 2024 that it had reached an agreement with the FDA to use an external control design to seek accelerated approval, the FDA recently rejected that plan and instead required a sham internal control study to support the application.
In two other recent rejections of rare disease candidates that also involved the use of external controls, the agency denied approval for Regenxbio’s Hunter syndrome gene therapy and also rejected Biohaven’s troliluzole for spinocerebellar ataxia.
In a recent interview with Fierce Biotech, Biohaven CEO Dr. Vlad Choric blamed “systemic problems” at the FDA and warned that “devastating times” are ahead for rare disease patients.
Following the FDA’s controversial move, Republican Sen. Ron Johnson (Wisconsin) launched an investigation into the FDA’s rejection of rare disease drugs. And Dr. Vinay Prasad, the FDA official who heads the FDA’s Center for Biologics Evaluation and Research, which oversees gene therapy, will resign at the end of April.
Despite the regulatory uncertainty, Evaluate analysts argue that the fundamentals of the orphan drug sector remain “stable” and that “the core drivers of orphan drug research and development remain strong.” These incentives include legally mandated tax credits and market exclusivity.
Furthermore, the assessment report notes that the rare disease market remains largely untapped, as today’s orphan drugs address only approximately 5% of all rare diseases.
That doesn’t mean there won’t be more volatility down the road. Payers face increasing pressure to control costs as more rare disease treatments enter the market at higher prices.
China’s rise as a biotech powerhouse could exacerbate pricing pressures if molecules licensed from China face increased competition, Evaluate warns.
“Resurgent investor interest in biopharmaceuticals after several years of economic weakness could ease pricing and policy uncertainty surrounding orphan drugs,” the analysts said in their conclusion. “But these questions can cause investors to flock to what they know: proven methods in much larger markets.”
