Ionis gets a double whammy

On Friday Ionis touted positive mid-stage results with fesomersen, a member of a new class of anticoagulants. The data, in end-stage renal disease patients on dialysis, were clearly not enough to convince Bayer, however: Ionis’s erstwhile partner handed back rights, leaving the smaller group searching for a new collaborator. Bayer is more exposed than most to the factor XIs, a much-hyped class that threatens to disappoint after recent mid-stage failures for Bayer’s asundexian and Bristol Myers Squibb/Johnson & Johnson’s milvexian; the developers have pressed on into phase 3 regardless. Given the cost of these trials, it would not be surprising if Bayer opts to fully focus on asundexian – which could be bad news for another asset the two groups are partnered on, osocimab, due to yield data soon. Meanwhile, Ionis also expanded the phase 3 Cardio-TTRansform trial of eplontersen, its Astrazeneca-partnered amyloidosis project, in the cardiomyopathy disease subtype for a second time. Ionis pointed to earlier diagnosis, which could lead to lower numbers of cardiac events, but investors read the move as increasing the risk of a negative readout. The trial, which will now enroll 1,400 patients, is still set to report in the first half of 2025. Ionis’s stock closed down 7% on Friday.

Factor XI inhibitors in development
Project Company Description Trial details
Phase 3
Abelacimab (MAA868) Anthos Therapeutics (Novartis spin-out) Anti-factor XI & XIa MAb Cancer-associated VTEs: ph3 Aster vs Eliquis & Magnolia vs LMW heparin, both complete Sep 2023; ph2 Azalea-TIMI 71 vs Xarelto in AF, data due Q1 2023
Phase 2
Asundexian (BAY 2433334) Bayer Oral factor XIa inhibitor Pacific-AF vs Eliquis, data reported Apr 2022; Pacific-AMI & Pacific-Stroke failed to meet efficacy endpoints
Milvexian (BMS-986177) Bristol Myers Squibb/Johnson & Johnson Oral factor XIa inhibitor Axiomatic-TKR data positive; Axiomatic-SSP failed to meet efficacy endpoint
Fesomersen (BAY2976217/IONIS-FXI-LRx) Ionis Factor XI antisense RE-THINc ESRD, in ESRD pts on dialysis, met primary endpoint but Bayer handed back rights Nov 2022
Osocimab (BAY1213790) Bayer/Aronora Anti-factor XIa MAb Convert in ESRD pts on dialysis, data due H2 2022
MK-2060 Merck & Co Anti-Factor XI & XIa MAb MK-2060-007 in ESRD pts on dialysis, data due H1 2023
AB023 Aronora Anti-factor XI & XII MAb Ph2 data published in ESRD pts on dialysis; ph2 ongoing in cancer pts receiving chemo*
Phase 1
BMS-986209 Bristol Myers Squibb  Oral factor XIa inhibitor Completed ph1 Aug 2021
Ir-CPI Bioxodes Anti factor XI & XII protein Completed ph1 Jul 2020
*Investigator-sponsored. AF=atrial fibrillation; AMI=acute myocardial infarction; ESRD=end-stage renal disease; SSP=secondary stroke prevention; TKR=total knee replacement; Source: Evaluate Pharma &

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