Tafamidis

By 2032, rare disease drug sales will account for more than 21% of all prescription drugs, up from 15% in 2022, according to Evaluate's 2026 Orphan Drugs Report. The rare disease field is navigating a period of significant turbulence, caught between a “temperamental” FDA and competition for investor attention from mainstream blockbusters like obesity treatments. Yet, despite the “stormy waters,” global sales of orphan drugs are projected to grow and exceed $400 billion by 2032, according to the newly released 2026 Orphan Drugs Report from Evaluate.The massive $409 billion that rare disease treatments are forecast to generate in annual revenue represent more than 21% of the nearly $1.9 trillion in global prescription medicines sales worldwide in 2032. That marks an increase from 15% in 2022, according to the new report published Thursday, March 12. While the outlook is bullish, the journey to $400 billion is likely anything but a straight line. Despite a few recent policy wins such as an updated Inflation Reduction Act (IRA) exception and the reauthorization of the rare pediatric disease priority review voucher program, the market remains vulnerable to a more scrutinizing FDA and potential pricing pressures. Charting the growthTen existing therapies are expected to lead the pack as the bestselling orphan drugs in 2032, with eight of them projected to rake in more than $6 billion in annual sales each. Johnson & Johnson is poised to wear the orphan drug crown both as a company and from a product perspective.The company’s multiple myeloma therapy Darzalex (daratumumab) is projected to be the top-selling orphan drug with $11.8 billion in sales. While that marks a decline from the drug’s $14.4 billion sales in 2025, a subcutaneous formulation is extending its market exclusivity, effectively doubling the franchise’s commercial lifespan.J&J’s position is further bolstered by Legend Biotech-partnered multiple myeloma CAR-T therapy, Carvykti, which secures the No. 8 spot with $6.3 billion in forecast sales.Thanks to those meds, J&J will claim the title as the biggest company by orphan drug sales, with nearly $31 billion in projected revenue from this category in 2032, according to Evaluate.  Vertex is the other company with two drugs on the top 10 list. The Boston biotech’s Alyftrek, a once-daily triple combination for the treatment of cystic fibrosis, is poised to become the second-highest-selling orphan drug globally, with $9.3 billion in projected sales by 2032. Meanwhile, the firm’s older Trikafta will take the final spot with $4.9 billion in sales. Alnylam’s fast-growing transthyretin amyloidosis (ATTR) RNA interference drug Amvuttra (vutrisiran) is tipped to take third place, with $7.5 billion in 2032 sales. There have been some questions around the growth potential of the drug—and the entire ATTR market—given the expected loss of market exclusivity for Pfizer’s first-in-class tafamidis.  Perhaps the most dramatic shift in the rankings is the rise of argenx. Dubbed a “gate-crashing” force, argenx is forecast to displace Pfizer in the orphan drug sales rankings in 2032, driven by the successful launch of the autoimmune drug Vyvgart (efgartigimod alfa). The $11.2 billion in projected total orphan drug sales put the Dutch biotech in 8th place among companies, ahead of Merck & Co. ($9.9 billion) and Bristol Myers Squibb ($9.7 billion). Argenx also holds the distinction of being the only firm on Evaluate’s list with 2032 revenue derived entirely from orphan drugs. AstraZeneca’s complement inhibitor Ultomiris, Merck’s pulmonary arterial hypertension med Winrevair, BeOne Medicines’ blood cancer drug Brukinsa and Roche’s hemophilia A therapy Hemlibra round out the top orphan drugs list.Among the 10 companies, Merck boasts the fastest orphan sales increases, at 23% compound annual growth rate between 2025 and 2032, followed by argenx’s 22%.In contrast to an overall share gain of orphan drugs in the entire pharmaceutical market, their footprint in the R&D pipeline is beginning to shrink. Evaluate analysts expect the percentage of rare disease candidates in development within overall drug sales to fall from a projected peak of 30% in 2027 to 22% in 2032. “This likely reflects growing interest and investment in big drugs for big diseases—including most prominently GLP-1 based therapies,” Evaluate analysts noted. As large pharmas face a collective $300 billion patent cliff by the end of the decade, the need to develop drugs for large indications remains high, the team added. Policy pushes and pullsJ&J’s Darzalex and argenx’s Vyvgart get to protect their hefty sales outlooks thanks, in no small part, to a recent IRA revision. Under the original IRA, only drugs with single orphan indications were exempt from U.S. government price negotiations. As part of President Donald Trump’s One Big Beautiful Bill Act, the provision has expanded the orphan exemption to cover drugs with multiple indications. In another significant amendment that favors the industry, the countdown toward eligibility for price reduction under the IRA won’t start until after the first non-orphan approval.However, the regulatory environment has recently become unpredictable for rare disease drug developers, no thanks to what Evaluate calls “mixed signals” from the FDA.While the FDA has introduced the “plausible mechanism pathway” to accelerate individualized therapies targeting genetic abnormalities behind rare diseases, the agency has also turned down several rare disease drugs, fueling industrywide outcry. Prominent among these rebuffs is uniQure’s Huntington’s disease gene therapy candidate, AMT-130. The one-time therapy showed a 75% reduction in Huntington’s disease progression three years after treatment when compared with external control. However, after uniQure said in 2024 that it had reached an agreement with the FDA to use the external control design to seek an accelerated approval, the agency has recently rejected that plan, demanding instead an internal sham-controlled study to support an application. In two other recent rebuffs against rare disease candidates that also involve the use of external controls, the agency declined to approve Regenxbio’s Hunter syndrome gene therapy and rejected Biohaven’s troriluzole in spinocerebellar ataxia.In a recent interview with Fierce Biotech, Biohaven CEO Vlad Coric, M.D., decried a “systemic problem” at the FDA and warned of a “dire time” for rare disease patients.Following the FDA’s controversial moves, Republican Sen. Ron Johnson of Wisconsin has launched an investigation into the agency’s rejections for rare disease drugs. And FDA official Vinay Prasad, M.D., who leads the agency’s Center for Biologics Evaluation and Research overseeing gene therapies, is stepping down at the end of April. Despite the regulatory uncertainties, Evaluate analysts argue the fundamentals of the orphan drug sector remain “steady,” and that the “core drivers of orphan drug R&D remain strong.” These incentives include law-encoded tax credits and market exclusivities. Besides, the rare disease market remains largely untapped, as today’s orphan drugs only address roughly 5% of all rare conditions, the Evaluate report noted. That doesn’t mean there is no additional volatility ahead. As more rare disease drugs reach the market at high prices, payers face increased pressure to control costs.China’s rise as a biotech powerhouse might worsen the pricing pressure if molecules licensed from China add more competition, Evaluate warns. “Renewed investor interest in biopharma, after a multiyear downturn, may mitigate pricing and policy uncertainty around orphan drugs,” the analysts wrote in the concluding paragraph. “But those questions could just as likely send investors flocking to what they know: tried and tested modalities in much bigger markets.”