AEterna Zentaris Inc.'s stock-punishing Phase III blowup with cetrorelix for benign prostatic hyperplasia may have dampened some hopes for another late-stage trial under way in Europe, though AEterna cautioned against drawing any conclusions.
A bigger-than-expected placebo response registered not only higher than the company saw in Phase II trials, but beyond what's been noted in the literature describing other studies, said Paul Blake, AEterna's chief medical officer. That could mean the European results will be more encouraging.
"We hope that's the case," Blake said, adding that the firm is "still trying to understand the data" from the just-reported study, and stands behind cetrorelix.
News of the failure sent the Quebec-based firm's stock (NASDAQ:AEZS) down 60 percent Monday to close at $1.14, a drop of $1.69, less than six months after the deal with Paris-based Sanofi's U.S. affiliate put $30 million of up-front money in AEterna's pocket and boosted the stock by 33 percent to 95 cents. (See BioWorld Today, March 9, 2009.)
In the 667-patient, one-year North American trial, the drug - a reformulated injectable of AEterna's marketed product, Cetrotide, the gonadotropin-releasing hormone antagonist for in vitro fertilization - turned up no clear difference in efficacy from placebo with regard to the primary endpoint: a change in severity and stability of voiding symptoms based on the International Prostate Symptom Score.
The drug provided hints of improvement, at least. "The clearest separations we saw were at weeks 38 and 46, but by week 52 that difference was gone and it was virtually back to where the placebo is," Burke told BioWorld Today. A separate trial showed cetrorelix was safe and well tolerated.
In November, a second Phase III efficacy study in Europe is due to report data. AEterna has no plans to start another study in the meantime, but instead will analyze data from the North American research while waiting for the second set of results. "It would be premature to start anything else," Burke said.
Some patients try herbal remedies such as saw palmetto for BPH, while doctors often prescribe alpha blockers and 5 alpha reductase inhibitors. In the former category, Boehringer Ingelheim GmbH, of Ingelheim, Germany, has the strong-selling Flomax (tamsulosin). Big names in the latter category include Proscar (finasteride), from Whitehouse Station, N.J.-based Merck & Co. Inc., and Avodart (dutasteride), from GlaxoSmithKline plc, of London.
Alpha blockers, though, can cause cardiovascular side effects, especially postural hypotension (low blood pressure upon standing up), as well as erectile dysfunction and abnormal ejaculations. The 5 alpha reductase inhibitors are relatively well tolerated, though some patients notice a decrease in libido and breast enlargement.
Available therapies are daily pills. With cetrorelix - two shots given 14 days apart, to provide six months' worth of therapy - AEterna is shooting for better efficacy and fewer side effects as well as improved patient convenience.
Another BPH player is Nymox Pharmaceutical Corp., of Hasbrouck Heights, N.J., which is pushing NX-1207 through a Phase III program. Injected directly into the prostate, the compound so far has shown no cardiovascular or sexual side effects of the two popular classes of therapy, and follow-up studies of available subjects from trials suggested durable benefits for up to five years.
AEterna has more than cetrorelix in its hopper, including perifosine, an inhibitor of the PI3K/Akt pathway, partnered with Keryx Biopharmaceuticals Inc., of New York, in the U.S., Canada and Mexico. Keryx recently disclosed a special assessment protocol for its study in multiple myeloma. At the American Society of Clinical Oncology, Keryx reported positive Phase II results with perifosine in advanced metastatic colon cancer and advanced kidney cancer. (See BioWorld Today, June 2, 2009, and Aug. 4, 2009.)
At the Phase II stage, AEterna has AEZS-108, a cytotoxic peptide conjugate that yielded positive early results at ASCO. Continued expression of luteinizing hormone-releasing hormone receptors in prostate cancer specimens after prolonged use of LHRH agonists supports investigating the compound in hormone-refractory prostate cancer, the company said.