Shares tumble as trials fail

Several Phase II and III trials have recently produced disappointing data, resulting in the failure to meet primary and secondary endpoints. The impact of this can be huge for some of the smaller companies, causing share prices to drop considerably.

Of particular note, Curis, Roche and Genentech's Phase II trial of GDC-0449, a first-in-class Hedgehog pathway inhibitor, tested in combination with Avastin (bevacizumab) and FOLFOX or FOLFIRI chemotherapy in first-line metastatic colorectal cancer (MCRC) patients did not meet its primary endpoint of extending the time from randomisation to disease progression or death when compared to patients who received only the current standard-of-care treatment. As a result, Curis' share price sank by 48 per cent, whereas the company's stock had more than doubled during the past year until this point. Despite these disappointing results in MCRC, Curis remains encouraged that the clinical development of GDC-0449 in other cancers continues to make good progress.

Further disappointment arose for Bayer HealthCare and Onyx Pharmaceuticals, when a final analysis of the Phase III NExUS trial evaluating Nexavar (sorafenib) in patients with advanced non-squamous non-small cell lung cancer (NSCLC) showed that the study did not meet its primary endpoint of improving overall survival (OS) in the first-line setting, although a positive secondary endpoint of progression-free survival (PFS) was observed. The two companies are to further review the findings of this analysis to determine what, if any, impact these data might have on other ongoing clinical trials evaluating the safety and efficacy of sorafenib.

Marshall Edwards (Novogen) recently experienced a similar blow, when a final analysis of the company's Phase III OVATURE trial of orally-administered phenoxodiol in women with recurrent ovarian cancer determined that the study did not show a statistically significant improvement in its primary (PFS) or secondary (OS) endpoints. Following this news, the company's share price dropped by 50 per cent.

Also, in May, GTx reported top-line results of a Phase III trial evaluating toremifene 20mg for the prevention of prostate cancer (PCA) in men with high-grade prostatic intraepithelial neoplasia, which showed that the incidence of PCA was lower in men receiving the drug compared to placebo, but not statistically significantly different (p=0.385). A 10.2 per cent relative risk reduction at three years was observed. Following these results, the company's share price dropped by over 33 per cent. Dr Mitchell S Steiner, CEO of GTx, commented: "We designed the Phase III trial based upon the successful outcome of our Phase IIb clinical trial. Toremifene 20mg did also reduce prostate cancer in our Phase III study, but based on our review of the top-line data, there is not a sufficient reduction in cancers compared to placebo over a three-year period to demonstrate the statistical significance required for this study."

Alice Rossiter
Editor, Cancer Drug News