Participant registration begins in Phase III clinical trial of Japan’s first recombinant folliitropin alfa/lutropin alfa (FSH/LH) fixed-dose combination – Merck
Merck BioPharma K.K., the Japanese subsidiary of Merck KGaA, began participant registration for a Phase III trial evaluating the efficacy and safety of fixed-dose combinations of follitropin alfa and lutropin alfa, targeting Japanese women who may not be able to achieve sufficient follicle development with FSH monotherapy during ART (Assisted Reproduction) treatment. Currently, fixed-dose formulations containing LH are not approved in Japan, making this trial an important initiative to explore the potential of new therapeutic options in Japan.
This trial is a parallel two-group comparative trial comparing fixed-dose combinations of folliitropin alfa/lutropin alfa with hMG, evaluating the efficacy and safety in follicle development induction.
Infertility treatment is an important area where treatment choices are tailored to each patient’s condition. Therefore, exploring the potential for new therapeutic approaches through the creation of scientific evidence holds significant importance for both patients and healthcare professionals. Merck BioPharma sincerely addresses unmet needs in the field of infertility treatment and aims to create new drugs that contribute to patients.
About the Trial
This trial is a Phase III clinical trial evaluating the efficacy and safety of a fixed-dose combination of follitropin alfa/lutropin alfa in follicle development induction, targeting Japanese women who may not be adequately developed by FSH monotherapy during ART. In this trial, eligibility for participation will be determined based on the clinical trial protocol, confirming the eligibility of eligible participants. ClinicalTrials.gov Identifier：NCT07340827
Background
Merck developed follitropin alfa during the 1990s. It was commercialised as GONAL-f and became the first recombinant FSH available for fertility treatment and a major advance over older urinary-derived gonadotropins because it offered: consistent potency. high purity. unlimited manufacturing supply, and less batch-to-batch variability. Today GONAL-f is one of the best-known ovarian stimulation drugs worldwide.
Lutropin alfa (recombinant LH) is a recombinant human luteinising hormone (LH). LH has a different role from FSH. It stimulates ovarian theca cells, promotes androgen production, provides substrate for estradiol synthesis, and supports final follicular maturation. Merck commercialised recombinant LH as Luveris.
Unlike FSH, recombinant LH has always been a much more specialised medicine because most IVF patients produce sufficient endogenous LH. It is mainly used in women with severe LH deficiency, hypogonadotropic hypogonadism, selected poor responders.
For many years clinicians simply prescribed GONAL-f plus Luveris as two separate injections. Merck recognised that the same patients were routinely receiving both medicines, so it developed a single fixed-dose combination containing 150 IU follitropin alfa and 75 IU lutropin alfa. This became Pergoveris. The fixed-dose combination received its first EU marketing authorisation on 25 June 2007. A 2018 safety review noted that the combination had become authorised in more than 90 countries but not in Japan. Japan has historically been much more conservative in assisted reproduction. As a result recombinant FSH is available in Japan; urinary hMG is available; but a recombinant fixed-dose FSH/LH combination has never been approved. Merck is therefore running a dedicated Japanese Phase III study to satisfy PMDA requirements.
Most women undergoing IVF do not need additional LH. However, some women appear to benefit, including those with profound LH deficiency, hypogonadotropic hypogonadism, poor ovarian response, advanced maternal age, inadequate response to FSH alone. The Japanese announcement specifically targets women who may not achieve sufficient follicular development with FSH monotherapy. So this is a precision medicine approach rather than a treatment intended for all IVF patients. Obtaining Japanese approval for Pergoveris would fill one of the remaining gaps in Merck’s global fertility portfolio.
