Top R&D Candidates
Figure 6: Top 5 Orphan Drugs in 2032 (Phase III/ Filed) by NPV
The risks – in particular regulatory risks – inherent in orphan drug development are evident across the top ten most valuable pipeline orphans.
Until December 2025, the frontrunner orphan was relacorilant, a glucocorticoid receptor antagonist developed by Corcept Therapeutics for Cushing syndrome (hypercortisolism) and platinum-resistant ovarian cancer (PROC). Then FDA rejected the drug’s Cushing application due to insufficient evidence of efficacy and ongoing concerns over liver-related safety. (Another FDA change in 2025 was the decision to publish redacted copies of Complete Responses Letters promptly, rather than much later (or never), leaving developers with no room to cover up submission shortcomings.)The setback pushed relacorilant out of the top ten, but positive Phase 3 survival data published early this year in PROC, and an anticipated FDA decision for this indication in July 2026 continue to prop up overall sales forecasts for the drug, which is also being investigated in earlier-stage ovarian cancer and other solid tumors.
Daraxonrasib, a small molecule pan-RAS inhibitor developed by Revolution Medicines, uses several mechanisms to target multiple RAS mutations, including those found in most pancreatic tumors. The Phase 3 candidate’s $4 billion 2032 sales projection reflects the considerable unmet need in pancreatic cancer, due in part to the ineffectiveness of immunotherapy in this setting.
Gilead Sciences’ recently filed autologous CAR-T cell therapy anito-cel hits the same target (BCMA) as J&J’s top ten bestselling myeloma orphan Carvykti, helping reduce that drug’s risk profile. Gilead in February 2026 announced a $7.8 billion deal to acquire anito-cel originator and partner Arcellx, ostensibly to accelerate the drug’s reach across multiple myeloma and potentially into inflammation, and to leverage Arcellx’s technology to develop in vivo cell therapy (which does not involve cumbersome cell extraction and re-infusion processes).
In general, investment in first-generation (autologous) CAR-T therapies has cooled off over the last four years, due to the administrative and commercial challenges facing the category.
No such challenges face bispecific antibodies. AbbVie’s CD3xBCMA targeted multiple myeloma drug etentamig is worth $7 billion (in net present value (NPV) of projected worldwide sales), making it the fifth most valuable pipeline orphan. These dual-targeted antibodies, which direct T-cells to tumor-associated antigens, are fast-growing across oncology and– like CAR-T cell therapies - are also showing promise in autoimmune and inflammatory diseases, where they can deplete disease-causing B-cells.
Bispecific antibodies have been a major focus of dealmaking involving Chinese originator companies. Chinese biotechs are generating potentially best-in-class molecules at a fraction of the cost – and time – required in many Western countries. China’s rise is impacting most therapy areas and modalities and is reflected in the share of FDA orphan designations assigned to China-based sponsors, which rose from less than 5% in 2020 to 15% in 20254.
Chinese biotechs are generating potentially best-in-class molecules at a fraction of the cost – and time – required in many Western countries.
