Ono takes on Takeda in polycythemia vera
The Japanese group licenses sapablursen from Ionis for $280m.
The Japanese group licenses sapablursen from Ionis for $280m.
Takeda recently bagged a phase 3 win with rusfertide in the rare blood cancer polycythemia vera, and now its Japanese rival Ono has decided that it wants a piece of this market, licensing sapablursen from Ionis for $280m up front.
The fee echoes the $300m that Takeda paid to get its hands on rusfertide, originally developed by Protagonist. However, rusfertide was already in pivotal development when that deal was struck, while sapablursen is still in phase 2.
Polycythemia vera involves the overproduction of red blood cells, and the two projects have the same ultimate goal: to increase levels of hepcidin, a key regulator of homeostasis, thereby lowering red blood cell production.
However, rusfertide is a straightforward hepcidin mimetic, while sapablursen is an antisense oligonucleotide designed to block expression of TMPRSS6, a protease that negatively regulates hepcidin.
Silence Therapeutics is also attempting to hit TMPRSS6, with divesiran, although this project is a small interfering RNA rather than an ASO. Agios also has a TMPRSS6-targeting siRNA, AG-236, in preclinical development; it licensed the asset from Alnylam in 2023.
Novel agents in clinical development for polycythemia vera
| Project | Company | Description | Key trial(s) | Note |
|---|---|---|---|---|
| Jakafi | Novartis/ Incyte | JAK inhibitor | Ph3 Response | FDA approved post-hydroxyurea Dec 2014 |
| Rusfertide | Takeda/ Protagonist | Hepcidin mimetic | Ph3 Verify | Toplined positive Mar 2025 |
| Givinostat | Italfarmaco | HDAC inhibitor | Ph3 GIV-IN PV | Completes Jul 2026 |
| Bomedemstat | Merck & Co (via Imago) | LSD1 inhibitor | Ph2 MK-3543-004 | Completes Mar 2025; lead indication is essential thrombocythemia |
| Sapablursen | Ono/Ionis | Anti-TMPRSS6 antisense oligonucleotide | Ph2 Imprssion | Completes Jun 2025 |
| Divesiran (SLN124) | Silence Therapeutics | Anti-TMPRSS6 siRNA | Ph1/2 Sanreco | Ph1 data reported Jun 2024; ph2 portion under way |
| PPMX-T003 | Perseus Proteomics | Anti-TfR1 MAb | Ph1 | Data at ASH 2023 |
| MWTX-003 | Disc Medicine/ Mabwell | Anti-TMPRSS6 MAb | China ph1 | Completes Aug 2025 |
Source: OncologyPipeline.
One potential advantage with the RNA-targeting therapies could be convenience. All three projects are given subcutaneously: rusfertide once weekly, sapablursen every four weeks, and divesiran every six weeks.
Whether this will be enough to make a difference is another question. And with rusfertide heading to regulators by the end of this year, sapablursen and divesiran are well behind.
First Imprssion
Sapablursen is in the phase 2 Imprssion trial, with data expected this year. Like the phase 3 Verify study of rusfertide, Imprssion recruited patients dependent on phlebotomy (blood removal), the current mainstay of therapy.
Imprssion, which is uncontrolled, will primarily measure the change in frequency of phlebotomy. Ionis remains responsible for Imprssion, while Ono will take over subsequent development.
Silence’s divesiran, meanwhile, is in a phase 1/2 study called Sanreco, which showed promising phlebotomy reduction in its phase 1 portion last year, and has moved into phase 2, with full enrolment expected by year end.
One big question for Takeda and its rivals is the size of the market. Polycythemia vera affects around 100,000 patients in the US, and Protagonist has previously estimated that rusfertide could generate peak sales of $2bn.
This seems like a limited pie to share between three players, but Ono clearly sees promise here – and it’s spending much less than it did on another recent deal, the $2.4bn purchase of Deciphera. Meanwhile, for Ionis the deal makes sense given that group’s extensive pipeline, much of which is already partnered.
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