Onconova Plunges As Phase-3 ONTIME Trial Of Rigosertib Fails To Meet Main Goal

(RTTNews) - Onconova Therapeutics Inc. (ONTX), a clinical-stage biopharmaceutical company, said Wednesday that the Phase 3 ONTIME trial of intravenous rigosertib in patients with higher risk myelodysplastic syndromes who had progressed on, failed or relapsed after prior therapy with hypomethylating agents did not meet the primary endpoint of overall survival compared to best supportive care.

Following the announcement, Onconova shares tumbled 45 percent in after-hours trade on the Nasdaq.

The ONTIME trial enrolled 299 patients including 199 patients in the intravenous (IV) rigosertib plus best supportive care (BSC) arm. Median overall survival in the IV rigosertib plus BSC arm was 8.2 months compared to 5.8 months in BSC only arm, the company said.

Treatment with IV rigosertib plus BSC did not demonstrate a statistically significant improvement in median overall survival when compared to BSC only.

However, a post-hoc analysis showed a statistically significant increase in median overall survival in the subset of patients who had progressed on or failed previous treatment with hypomethylating agents (HMAs) (i.e., had not responded to HMAs), thus demonstrating potential activity of rigosertib in these myelodysplastic syndromes (MDS) patients.

In this subset of patients (184 of 299 enrolled patients), the median overall survival was 8.5 months in the IV rigosertib plus BSC arm compared to 4.7 months in BSC only arm. Additional analysis is underway to identify potential survival benefit in other subsets of patients, the company said.

Preliminary safety analysis indicates that rigosertib was generally well tolerated in the study population. Severe adverse events were uncommon, with a similar profile of serious adverse events in both study arms.

Grade 3/4 treatment-related hematologic and non-hematologic adverse events were reported in less than 7% and 3% of patients, respectively. Incidence of all grades of treatment-related nausea, diarrhea, fatigue and constipation were 22%, 17%, 17%, and 15%, respectively.

The company said additional details will be presented at the 2014 ASCO Annual Meeting.

"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," said CEO Ramesh Kumar.

"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," said Kumar.

Onconova stock closed Wednesday at $13.86, down $0.01 or 0.07%, on a volume of 92 thousand shares on the Nasdaq. In after hours, the stock plunged $6.76 or 48.77% at $7.10.