Top Ten Orphans In 2028: Shake Up

The ten most valuable orphan drugs will collectively generate over $57 billion in 2028. The top three are unchanged: Johnson & Johnson’s blood cancer drug Darzalex, Vertex’s Trikafta for cystic fibrosis and Roche’s haemophilia A treatment Hemlibra. But, in the last year, there has been a shake-up further down the ranks due to greater competition in some rare diseases and the Inflation Reduction Act.

Over the past year, growing competition and the IRA have shaken up rankings beneath top three Darzalex, Trikafta and Hemlibra

Top 10 Selling Orphan Drugs in 2028 by Worldwide Sales

BRUKINSA EDGES OUT IMBRUVICA, CALQUENCE
AbbVie’s blood cancer behemoth Imbruvica has been edged out by a newer Bruton’s tyrosine kinase (BTK) inhibitor, Beigene’s Brukinsa. Brukinsa beat Imbruvica in a 2022 head-to-head trial in previously treated chronic lymphocytic leukaemia and small lymphocytic lymphoma patients, perhaps due to its greater BTK specificity. New top-ten lister Brukinsa may also have a pharmacokinetic edge over AstraZeneca’s same-class drug Calquence, whose forecast 2028 sales ranking has slipped from fifth to seventh over the past year.

Worldwide Top 10 Selling Orphan Drugs in 2028
Rank	Product	Therapeutic Category	Worldwide Product Sales ($bn)	Company
1	Darzalex	Oncology	17,022	Johnson & Johnson
2	Trikafta	Respiratory	8,753	Vertex Pharmaceuticals
3	Hemlibra	Blood	6,203	Roche & Chugai Pharmaceutical
4	Ultomiris	Immunomodulators	5,184	AstraZeneca
5	Carvykti	Oncology	4,406	Johnson & Johnson & Legend Biotech
6	Jakafi	Oncology	4,235	Incyte & Novartis
7	Calquence	Oncology	4,016	AstraZeneca
8	Brukinsa	Oncology	3,835	BeiGene
9	Lynparza	Oncology	3,451	AstraZeneca
10	Venclexta	Oncology	3,344	AbbVie
Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. Worldwide sales represent sales for all indications. All sales analysis based on Evaluate Pharma’s ‘Orphan’ sub-set of products, as defined in the Appendix.

VYVGART SLIPS AMID COMPETITION
Argenx’s efgartigimod alfa (Vyvgart) drops to 14^th with $3 billion in forecast 2028 sales. It treats generalized myasthenia gravis (MG), a neuromuscular disease, and faces growing competition. UCB Pharma had two new MG drugs approved in 2023, Zylbrysq (zilucoplan), a targeted complement 5 inhibitor, and neonatal Fc receptor-targeting antibody Rystiggo (rozanolixizumab). And Johnson & Johnson’s pipeline contender nipocalimab, which works similarly to Rystiggo, in early February 2024 delivered positive Phase 3 results in MG. With its host of further designations – across Sjogren’s disease, autoimmune hemolytic anemia, inflammatory demyelinating polyneuropathy, and more – nipocalimab features in the top five orphans by net present value (NPV).Roche’s spinal muscular atrophy therapy Evrysdi also slips out of the top ten, to 18^th, despite gaining additional US and EU approvals in 2023 for infants under two months and posting positive one-year data in pre-symptomatic babies. Evrysdi (risdiplam), given orally, competes on convenience with Biogen’s antisense drug Spinraza (nusinersen) which is injected into the spinal cord, and Novartis’ gene therapy Zolgensma, given as a one-time IV infusion. Alongside Brukinsa, there were two other top-ten newcomers. Incyte/Novartis’ JAK inhibitor Jakafi’s sales forecasts were boosted by a delay to anticipated patent expiry (from 2027 to 2028), moving the myelofibrosis drug up from 11^th to 6^th. Johnson & Johnson’s Carvykti became the first CAR-T cell therapy to feature on the top ten 2028 list as this modality finds its feet. Carvykti’s 2028 sales are expected to top $4.4 billion despite an FDA class-wide safety review that led to mandatory label changes.