Ferring Pharmaceuticals

Press Release

Study appears in Today’s Therapeutic Trends

SUFFERN, NY – February 10, 2003 – According to a new study published in the First Quarter 2003 issue of Today’s Therapeutic Trends, Bravelle^® (urofollitropin for injection, purified), a highly purified human-derived follicle-stimulating hormone (hFSH), administered subcutaneously (SC), is effective and well tolerated for inducing oocyte development in donors for use in in vitro fertilization (IVF) patients. The study also resulted in excellent rates of implantation and pregnancies. Bravelle^® was approved by the U.S. Food and Drug Administration (FDA) on May 6, 2002 for ovulation induction (OI) and on December 19, 2002 for IVF.

“This study confirms that Bravelle^® is effective for controlled ovarian hyperstimulation for IVF in oocyte donors, and that the resulting embryos can be successfully transferred to recipients, leading to high pregnancy rates without high multiple births,” said Kenneth B. Kashkin, M.D., vice president, medical and regulatory affairs. “Not only can the results help infertility specialists determine optimum stimulation protocols for their donor patients, but the study also contributes to Ferring’s comprehensive body of clinical research on current treatment approaches in assisted reproductive technology (ART).”

Study Design
Bravelle^® SC was tested for efficacy and safety in its ability to induce oocyte development in donors for IVF procedures in an open-label, single arm, multicenter trial in 39 donors, ages 21 to 33, and 39 recipients, ages 28 to 48. Bravelle^® SC was administered for up to 12 days in oocyte donors who were successfully down-regulated (achieved pituitary suppression). When patients produced at least three follicles with diameters ≥ 16 mm and estradiol levels were within acceptable limits, human chorionic gonadotropin (hCG) was administered, and oocytes were retrieved. A maximum of four embryos were transferred to each recipient.

The primary outcome measure was the mean number of oocytes retrieved for donor subjects. Secondary outcome measures included the mean daily and total dose of FSH, the mean number of days of gonadotropin stimulation, the percentage of subjects who received hCG and underwent oocyte retrieval, the mean peak serum E2 levels, and chemical, clinical and ongoing pregnancy rates. Safety was measured by the numbers of patients reporting adverse events.

Study findings
All 39 donors treated with Bravelle^® received hCG and underwent oocyte retrieval. The mean daily FSH dose was 239.7 ± 50.8 IU, and mean number of days of stimulation was 8.9 ± 1.3. The mean number of total oocytes and mature oocytes retrieved was 15.5 ± 7.9 and 12.3 ± 7.7. Oocytes of 38 subjects underwent fertilization and embryo transfer. The mean number of embryos transferred per recipient was 2.7 ± 0.89. Of the 38 recipients:

• 73.7% achieved chemical pregnancies;
• 63.2%, clinical pregnancies; and
• 55.3%, continuing pregnancies.

Thirteen recipients had singleton pregnancies, eight had twin pregnancies, and there were no other multiple pregnancies. The treatment was well tolerated, with nearly all adverse events in donors mild to moderate and of the nature expected with this class of medication. The data confirm that Bravelle^® produces predictable ovarian follicular growth and development in oocyte donors with excellent pregnancy rates in recipients.

Only physicians thoroughly familiar with infertility treatment, including the risk of multiple births and adverse reactions, should prescribe Bravelle^®. Like all gonadotropins, Bravelle^® is a potent substance capable of causing mild to severe adverse reactions, including ovarian hyperstimulation syndrome (incidence of 6.8%), with or without pulmonary or vascular complications, in women undergoing therapy for infertility.

Like other products for ovarian stimulation, treatment with Bravelle^® may result in multiple gestations.

About Bravelle^®
Bravelle^®, a highly purified human-derived follicle-stimulating hormone (hFSH) for infertility treatment, contains 75 IU of FSH and up to 2 percent LH activity. Bravelle^® is marketed by Ferring Pharmaceuticals Inc., a world leader in naturally occurring protein hormones.

Bravelle^®, administered SC or IM in conjunction with hCG, is indicated for ovulation induction following pituitary suppression. Bravelle^®, administered SC in conjunction with hCG, is also indicated for multiple follicular development during ART cycles in patients who have previously received pituitary suppression.

Background on Human-Derived Hormones
The key differences in human-derived and genetically engineered infertility treatments are raw material sources and cost. Human-derived FSH treatments are highly purified follitropins refined from the urine of postmenopausal women. By comparison, genetically engineered products are extracted from the secretions from Chinese hamster ovary cells that are cultured in fetal calf or other mammalian serum, and approximate human hormones. Both are manufactured in compliance with extremely strict standards (including viral inactivation and confirmatory testing), but human-derived products are generally less expensive than their genetically engineered counterparts.

About Ferring
Ferring Pharmaceuticals, part of the Ferring Group, a privately owned, international pharmaceutical company, markets Bravelle^®, Repronex^® and Novarel™ in the U.S. to infertility specialists and their patients. The Ferring Group specializes in the research, development and commercialization of compounds in general and pediatric endocrinology, urology, gastroenterology, obstetrics/ gynecology and infertility. For more information, call 1-888-337-7464 or visit www.ferringusa.com.