Onconova reports PhIII flop, putting high-risk MDS program on the chopping block
Beleaguered biotech Onconova ran into another setback Monday morning as a Phase III for its lead program flopped once again.
The trial results for rigosertib, which blocks cellular signaling by targeting RAS effector pathways, in high-risk myelodysplastic syndrome patients did not meet its primary endpoint of improved survival. In individuals who had tried and failed treatment with a hypomethylating agent, rigosertib plus best supportive care achieved overall survival of 6.4 months, compared to 6.3 months for patients on physician’s choice.
“Onconova would like to thank the MDS community for its participation in the INSPIRE trial,” president and CEO Steven Fruchtman said in a morning call with investors. “We report these results with great disappointment.”
Monday’s news sent Onconova $ONTX shares, which had already been nearing penny-stock territory, spiraling almost 70% in early trading.
The final results came as a bit of a shock to the company, as rigosertib’s MDS program indicated positive interim results in early 2018 — enough to cause Onconova to expand its trial from 225 to 360 patients.
But an unexpected shift occurred in the physician’s choice arm following the interim readout, causing a “dramatic” improvement in survival. Given that there were no new outside developments in the high-risk MDS field that might have caused the increase, Fruchtman said it remained unclear what sparked such a spike in survival.
“The physician’s choice has been consistent for the last decade,” Fruchtman said, “so we do not understand why there was a marked improvement in survival on the physician’s choice arm compared to historical studies. We will continue to try to explore that to gain additional understanding.”
Fruchtman added that, in regards to potential additional agents associated with MDS, the company has already taken a look at things like bone marrow transplants and after “preliminary review” use of such agents appear to be “quite equal” in both trial arms.
This marks the second time rigosertib has sputtered in the Phase III stage, with the last occurrence in 2014, and the third time overall it’s suffered a clinical setback. Collaborations with Baxalta and HanX also broke apart over the years, with the former causing a company restructuring and the latter coming after the Chinese company failed to make required payments.
The newest failure will result in Onconova axing the rigosertib program for MDS treatments, though the company will continue to pursue efforts in other areas. Currently, Onconova is researching the compound in a Phase I/IIa study in KRAS-positive lung adenocarcinoma and hopes to expand efforts in other solid tumor types.
Moving forward, Onconova is preparing an IND submission for the ON 123300 program to treat CDK4/6 overactive tumors sometime before the end of the year.