Onconova hammered after top drug rigosertib flunks key PhIII study

A new wave of biotech investors is learning just how risky the drug development game can be. Onconova, which went public last year with the big class of 2013, says that its late-stage study of rigosertib for high-risk myelodysplastic syndromes failed to achieve a statistically significant improvement in overall survival compared to standard supportive care. Management of the Newton, PA-based biotech failed to switch the focus to a subgroup analysis that did highlight an improvement, and the biotech's shares cratered, plunging 37% in after-market trading.

This Phase III program was Onconova's ($ONTX) big selling point when the biotech went out to tout its prospects to institutional investors last year, winning a strong response that drove its share price above its range. The company reported a failure for its key drug just a few months ago, when rigosertib failed against pancreatic cancer. But this was the big show.

Investigators compared the drug with best supportive care in a population of MDS patients who had failed, progressed or relapsed on hypomethylating agents. The syndrome is a blood disorder characterized by a plunge in healthy blood cell counts. Median OS for the drug patients was 8.2 months compared to 5.8 months for best supportive care, falling short of the improvement the biotech was looking for. A subgroup analysis--always controversial in drug research--demonstrated a better response for patients who had not responded to earlier therapy, taking out the relapsed patients.

Post-hoc analysis wasn't the point of the study, though, and investors were routed by the bad news. The verdict also counts against Baxter ($BAX), which inlicensed the drug's European rights for $50 million upfront in a $500 million-plus deal.

Onconova management doesn't have a lot of options to turn to now. And they're sticking with rigosertib.

"While we are disappointed that the ONTIME trial did not meet its primary endpoint, we are encouraged by the significant treatment benefit seen in the subset of patients who had progressed on or failed HMAs i.e., patients who had not responded to prior HMA treatment. We look forward to presenting additional information after data analysis is completed," said Ramesh Kumar, the CEO of Onconova, in a statement. "We are working closely with our partners, Baxter and SymBio, as we evaluate the results of this study. We plan to engage with the U.S. Food and Drug Administration and European regulatory agencies with the goal of determining the next steps in advancing development of rigosertib for this underserved patient population. We remain committed to advancing rigosertib to address important medical needs in MDS and solid tumors. Ongoing efforts include trials of oral rigosertib in transfusion-dependent lower risk MDS patients, where, after consultation with regulatory agencies, we are planning to initiate a Phase III trial as soon as possible."

- here's the release

Suggested Articles

Fifteen of the 22 patients in a gene therapy trial no longer needed transfusions, while the remainder needed fewer transfusions.

Argos Therapeutics is ending its kidney cancer trial and mulling options, including a merger or sale, to stay alive.

CNS Pharma says berubicin is the first anthracycline drug to cross the blood-brain barrier and could transform treatment of the highly invasive brain tumor.