Oxigene designed a wrong positive control in the phase II study of fosbretabulin

On November 10, Oxigene (NASDAQ: OXGN) disclosed positive results from the GOG 186I (phase II) study of fosbretabulin combined with bevacizumab in recurrent ovarian cancer. However, shares of Oxigene slumped.

Median progression-free survival (PFS) was 7.3 months for bevacizumab plus fosbretabulin (n=54) compared to 4.8 months with bevacizumab (n= 53). The benefit was just barely statistically significant because the p value is 0.049. In the post-hoc subgroup analysis, for 27 platinum-resistant patients, median PFS was 6.7 months for bevacizumab plus fosbretabulin compared to 3.4 months for bevacizumab alone (p=0.01, HR=0.57). Patients in the combination arm experienced an increased incidence of Grade 3 hypertension compared to bevacizumab alone (31.5% vs. 18.9%).

The phase II data were positive. However, an analysis from Adam Feuerstein crushed investors’ positiveness. Bevacizumab monotherapy hasn’t been approved for the treatment of ovarian cancer. Oxigene’s phase II study doesn’t make sense.

Roche has completed the AURELIA study (phase III)[1] which demonstrated that adding bevacizumab to chemotherapy (liposomal doxorubicin, paclitaxel, topotecan) led to a statistically significant improvement in PFS over chemotherapy alone (6.7 vs. 3.4 months), but there was no overall survival benefit (16.6 vs. 13.3 months). The FDA has accepted Roche’s supplemental Biologics License Application (sBLA) and granted Priority Review.

Accurately, fosbretabulin, also known as Combretastatin A-4 phosphate, belongs to chemotherapy. The median PFS results from Oxigene’s GOG 186I study and Roche’s AURELIA study are exactly the same. Now, Oxigene has the wolf by the ear. If bevacizumab plus chemotherapy is approved by the FDA, Oxigene might try to conduct a non-inferiority study which requires huge numbers of patients; and if Roche’s sBLA is rejected, game over.

Several Chinese pharmaceutical companies have submitted INDs for Combretastatin derivatives (康普立停, 康普瑞丁磷酸二钠, C118P, etc.). However, the proof of concept has not been established.

[1] J Clin Oncol. 2014, 32(13), 1302-1308.

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