Modalities’ Mixed Fortunes

Three new gene therapies were approved in 2024: PTC Therapeutics’ Kebilidi for a rare neurological disorder, AADC; Orchard Therapeutics’ Lenmeldy for lysosomal storage disorder MLD and Pfizer’s Beqvez for hemophilia B. These, with the trio of new cell therapies, mean there are now more than two dozen cell and gene therapies on the US market. Yet investors have gone cool on the category, because of manufacturing and administrative complexity, high prices, and a shortage of clinical expertise. What is hot, though, is bispecific antibodies – alone, or, increasingly, as part of antibody-drug-conjugates (ADCs). Three new standalone bispecifics were approved in 2024, including Jazz Pharmaceuticals’ HER-2 bispecific Ziihera for biliary tract cancer and Merus’ Bizengri (HER2/HER3) for non-small cell lung cancer. The pair of new oligo-based drugs – Ionis’ Tryngolza and Geron’s Rytelo for blood cell cancer myelodysplastic syndrome – also underscore continued momentum in this category.There were no new ADCs or radio-ligand therapies (RLTs) in 2024, although dealmaker and investor enthusiasm remains high (see Avenzo’s latest ADC licensing deal, and purchases by RLT players Telix and Lantheus Holdings, for instance). This year may prove more fruitful, with four potential ADC approvals: AstraZeneca/Daiichi Sankyo’s TROP2 directed Dato-Dx, slated for an end-January decision; Merck/Daiichi’s HER3-DXd, delayed last year by manufacturing issues; AbbVie’s Teliso-V (submitted) and GSK’s Blenrep, withdrawn in 2023 as a multiple myeloma monotherapy but re-submitted last year for use in combination. In the RLT space, BMS’ actinium-225-based RYZ101 (from its $4.1 billion RayzeBio buy in early 2024) is among the leaders slated to soon join Novartis’ marketed Lutathera and Pluvicto; it’s in Phase 3 testing for gastroenteropancreatic neuroendocrine tumors, the same indication as Lutathera.

There are now more than two dozen cell and gene therapies
on the US market.