Ono chases Takeda in polycythemia

Takeda looks increasingly likely to reach the market by the end of this year with rusfertide in polycythemia vera, giving it first-mover advantage in a space that might offer limited room for multiple entrants. But Ono Pharmaceutical is nevertheless pressing ahead with its own contender, sapablursen, acquired from Ionis last year. 

Ono plans to launch a pivotal trial of sapablursen in mid-2026, according to a recently posted study on clinicaltrials.gov. This will enrol patients with polycythemia vera who are dependent on phlebotomy, a procedure in which blood is periodically removed from the body to reduce the excess red blood cells that characterise the disease, and to lower the risk of blood clots. 

The study's primary endpoint will be response rate, defined as the absence of phlebotomy eligibility. Its start marks the next step for the antisense therapy that Ono licensed from Ionis Pharmaceuticals in a deal worth $280m up front just over a year ago.

Still, Ono is running behind Takeda's rusfertide in a disease that affects only about 100,000 US patients per year. Rusfertide is already awaiting approval for polycythemia vera on the strength of the Verify trial, where it delivered a 77% response rate compared with 33% in the control cohort. 

The filing has a PDUFA date in the third quarter, and if the therapy is approved it could establish itself in what Protagonist, rusfertide's originator, estimated to be a relatively constrained $1-2bn market. Takeda licensed rusfertide from Protagonist in 2024 for $300m up front, and Protagonist stands to receive $400m if, as expected, it opts out of a profit-share deal.

Mimetic vs antisense

Even so, sapablursen could still have a place in the market. 

While rusfertide works as a hepcidin mimetic and requires weekly administration, Ono's candidate is an antisense oligonucleotide targeting TMPRSS6, a protease that negatively regulates hepcidin. Sapablursen is administered once every four weeks, a potential convenience advantage for patients.

For now, however, the programme remains behind rusfertide. In the phase 2 Imprssion study sapablursen met its primary endpoint, significantly reducing weekly phlebotomy rates from baseline between weeks 17 and 37. 

Whether that signal can translate into success and challenge Takeda's apparent head start will depend on the results of the pivotal trial, which has a completion date in 2028.  

Selected pivotal trials in polycythemia vera

Source: OncologyPipeline.