EU Approves First Long-Acting Fertility Treatment

Yael Waknine

February 02, 2010

February 2, 2010 — The European Commission (EC) has approved corifollitropin alfa subcutaneous injection (Elonva, Merck and Company, Inc), the first sustained follicle stimulant.

Corifollitropin is indicated for controlled ovarian stimulation (COS) in combination with a gonadotropin-releasing hormone antagonist for the development of multiple follicles in women participating in an assisted reproductive technology program.

"Since the birth of the first IVF baby, infertility treatment has undergone tremendous advancements. The aim [of] these changes is not just to use safer, more effective treatments but to increase patient compliance as well," Peter Kovacs, MD, Medical director of the Kaali Institute IVF Center in Budapest, Hungary told Medscape Ob/Gyn & Women's Health. "The introduction of the long-acting follicle stimulating hormone (FSH; corifollitropin alpha) is another step towards increasing patient compliance."

Due to a 2.5-fold increase in half-life, the long-acting version of FSH can be used to replace the first 7 injections of any conventional daily recombinant FSH (rFSH) preparation in a COS cycle.

"This is very exciting news, as this drug represents the first long-acting fertility drug currently approved for use," Hilton I. Kort, MD, a founding partner of Reproductive Biology Associates in Atlanta, Georgia, told Medscape Ob/Gyn & Women's Health. "Traditionally, fertility drugs for assisted reproductive technology require daily injections for 8 to 12 days combined with frequent blood tests and ultrasounds to monitor the patient's response to the medication. The new drug will replace the first 7 days of injections and reduce the frequency of monitoring and associated costs." Dr. Kort has worked in the field of infertility and in vitro fertilization for more than 30 years.

EC approval was based on data from the largest double-blind fertility agent trial performed to date (ENGAGE; n = 1506; participants < 37 years). The trial showed that the ongoing pregnancy rate was similar for patients receiving a single injection of 150 μg corifollitropin and those given 200 IU rFSH daily during the first week of a COS cycle (38.9% vs 38.1%).

The number of oocytes retrieved per attempt was likewise similar between groups (13.7 ± 8.2 vs 12.5 ± 6.7), as was the mean number of good-quality embryos obtained at days 3 and 5, respectively (4.6 ± 4.3 vs 4.4 ± 3.9; 2.6 ± 3.3 vs 2.6 ± 3.1).

Further analysis revealed that both regimens achieved similar oocyte/embryo quality, as well as consistently high pregnancy outcomes regardless of fertilization procedure (IVF or intracytoplasmic sperm injection), number of embryos transferred (single or double), or day of embryo transfer (day 3 or 5).

"The ENGAGE trial, completed in the United States and Europe, demonstrated that the new drug is as effective as the traditional daily injections," Dr. Kort said.

Adverse events reported with use of corifollitropin in the study included pelvic pain (4.1%) and pelvic discomfort (5.5%), headache (3.2%), nausea (1.7%), fatigue (1.4%), and breast complaints, including tenderness (1.2%).

Although the long-acting drug was not linked to an increased risk for ovarian hyperstimulation syndrome (7.0% [1.9% severe]) compared with rFSH (6.3% [1.3% severe]), the probability for this adverse event may theoretically be increased by off-label use or administration of higher doses.

"It is recommended that [corifollitropin] be prescribed only by trained reproductive endocrinologists," advised Dr. Kort.

"Not all patients could equally benefit from the use of corifollitropin alfa," Dr. Kovacs noted. "Those that are at risk for hyperstimulation or those who are likely to have poor response to stimulation still should be managed using daily injections to allow for more frequent dose adjustments."

He added, "In carefully selected patients, this new preparation is likely to become popular soon, as the number of injections, office visits, and potentially treatment costs can be reduced. Future studies will need to assess these benefits as well as its use as part of other stimulation protocols."

With the EC approval, Merck has obtained marketing authorization for corifollitropin with unified labeling valid in all European Union member states.

A company representative told Medscape Ob/Gyn & Women's Health that Merck has not yet disclosed its filing plan for the product in the United States.

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