About a year after regaining rights to cetrorelix in benign prostate hyperplasia, AEterna Zentaris Inc. received the rest of the rights to the luteinizing hormone-releasing hormone antagonist back from former partner Solvay Pharmaceuticals Inc.
"This is not something I anticipated when I joined the company a month ago, but I'm not particularly dissatisfied or unhappy with the result," said David Mazzo, president and CEO of Quebec City, Quebec-based AEterna Zentaris.
Shares of the company (NASDAQ:AEZS) dipped a scant 17 cents on Tuesday to close at $3.82. The absence of a knee-jerk sell-off in the wake of Solvay's decision to drop the product indicates that, like Mazzo, investors saw some positive aspects to the deal.
For starters, AEterna Zentaris regained cetrorelix free of charge, even though Solvay had invested up-front fees, milestone payments and development costs since originally licensing the drug from Zentaris AG in 2002, just prior to its 2003 acquisition by AEterna Laboratories Inc. (See BioWorld Today, Jan. 2, 2003.)
Mazzo declined to specify the amount of fees and milestones received, but noted the money is "ours to keep," along with all data generated thus far and any remaining clinical material.
Mazzo also said he received "no indication" from Solvay that its decision to discontinue development of cetrorelix was due to anything but strategic reasons. Since its 2005 acquisition of Fournier Pharma, Marietta, Ga.-based Solvay has moved away from women's health to focus on cardiometabolics and neurosciences. As such, it also divested a portfolio of 17-beta hydroxysteroid dehydrogenase Type I inhibitors for endometriosis and breast cancer to QuatRx Pharmaceuticals Co. (See BioWorld Today, June 23, 2006.)
Indeed, the publicly available safety and efficacy data for cetrorelix are positive. In Phase II trials of nearly 500 benign prostate hyperplasia patients, the drug resulted in a statistically significant, dose-dependent improvement in BPH symptoms at higher doses, including an improvement in urinary flow, without chemical castration. Similarly, Phase II trials in endometriosis resulted in a statistically significant improvement in pain scores without reducing hormones to castration levels.
Safety data are available not just from clinical trials, but from administration of millions of doses of Cetrotide, the brand name for cetrorelix that is approved in more than 80 countries for in vitro fertilization. Merck Serono SA markets Cetrotide worldwide except in Japan, and reported ex-Japan sales of $26.3 million in 2006.
In Japan, Cetrotide is marketed by Nippon Kayaku Co. Ltd. and Shionogi & Co. Ltd. Shionogi also holds the rights to cetrorelix in Japan, but everywhere else, in all indications, the drug now belongs to AEterna Zentaris.
Even before Tuesday's news, a report from analyst David Martin at Dundee Securities Corp. called cetrorelix "undervalued in the stock" and said AEterna Zentaris is "undervalued based on the cerotide/cetrorelix/ozarelix franchise alone."
While cetrorelix is designed for benign indications such as BPH and endometriosis, ozarelix is a fourth-generation LHRH antagonist designed for both benign and malignant indications. Partner Spectrum Pharmaceuticals Inc., of Irvine, Calif., is conducting Phase IIb trials in BPH and prostate cancer.
LHRH agonists such as Lupron (leuprolide, TAP Pharmaceutical Products Inc. and Abbott Laboratories) and Zoladex (goseralin, AstraZeneca plc) often are used to treat prostate cancer. The agonists cause an initial surge of hormone that then suppresses further hormone production. LHRH antagonists, on the other hand, don't cause an initial surge and instead result in dose-dependent control over hormone levels, making them suitable for both life-threatening and less severe indications. In 2006, Lupron generated $892 million globally, while Zoladex generated $1 billion.
Moving forward, Mazzo plans to conduct a strategic analysis of AEterna Zentaris' pipeline. In the fall, he anticipates providing an update on the commercialization plan for cetrorelix in BPH, where a Phase III program is under way, as well as in endometriosis, where Solvay had initiated a Phase III program prior to discontinuing development.
Beyond Cerotide, cetrorelix and ozarelix, AEterna Zentaris has another LHRH antagonist, AEZS-108, in Phase I trials and several related compounds in the preclinical stage.
Outside of the LHRH space, the company markets Impavido with various partners for visceral and cutaneous leishmaniasis. Pipeline programs include the Phase II cancer drug perifosine, which is partnered with Keryx Biopharmaceuticals Inc.; the Phase I peptidomimetic growth hormone secretagogue AEZS-130, which is partnered with Ardana Bioscience Ltd.; and the Phase I tubulin and topoisomerase II inhibitor AEZS-112 for cancer, as well as numerous preclinical programs.