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Correction: The ongoing phase III study of rigosertib, known as ONTIME, does not allow the use of Celgene's Vidaza.
NEWTOWN, Pa. (
(ONTX - Get Report)
is unique among the recent spate of biotech initial public offerings in that its lead drug development program is only months away from phase III study results.
Rigosertib is a dual PI3K (alpha and beta) and PLK1 inhibitor. Onconova is conducting a phase III study in patients with high-risk myelodysplastic syndrome (MDS) that no longer responds to prior therapy. The company expects results in the fourth quarter or first quarter of 2014. [A separate phase II/III study of rigosertib in pancreatic cancer may read out in the same time frame.]
In addition, the company has ongoing phase II trials of rigosertib in low risk MDS and head and neck cancer. The depth of the rogsertib clinical program provides Onconova multiple shots on goal and is a good risk/reward at these levels.
Onconova's near-term prospects will be driven by expectations of the phase III trial in high-risk MDS. The so-called ONTIME trial compares rigosertib infusion plus best supportive care versus best supportive care alone. The trial is being conducted under a Special Protocol Assessment reached with FDA. The study's primary endpoint is overall survival.
The control group is best supportive care simply because there is no approved drug for this indication, which in some ways creates a very low hurdle for rigosertib. The most important question: What is the expected survival for high-risk MDS patients treated with best supportive care?
Prebet et al (2011) is one of the few studies that looks at high-risk MDS after Vidaza failures and finds a median overall survival of 5.6 months (22 weeks), although patients were treated with various regimens. For the sub-set of patients receiving best supportive care, the median overall survival was 4.1 months, or 16 weeks. The study found three treatment regimes that produced a statistically significant benefit to best supportive care: Intensive chemotherapy (median overall survival 8.9 months), combination of various investigational treatments (median overall survival 13.2 months), and allogenic transplant (median overall survival 19.5 months.)
The Onconova phase III trial is powered to detect a 10-13 week benefit in median overall survival. If we assume best supportive care patients will live for 16 weeks, this means rigosertib has to demonstrate a median overall survival of 26 weeks for the study to be a success.
A more conservative assumption would be to assume control-arm patients live 22 weeks, which means rigosertib has to deliver 35 weeks of overall survival in the study.
The phase I/II trial of rigosertib in MDS showed a median overall survival of 10.1 months, or 40 weeks, but this result needs further clarification because the analysis encompassed only those patients who responded to treatment and not the overall intent-to-treat population. The "real" or intent-to-treat median overall survival in the phase I/II study was approximately 35 weeks.