VILAPRISAN, A NEW SELECTIVE PROGESTERONE RECEPTOR MODULATOR IN UTERINE FIBROID PHARMACOTHERAPY - WILL IT REALLY BE A BREAKTHROUGH?

Background: Vilaprisan (VPR) is a new orally available selective progesterone receptor modulator (SPRM), with anti-proliferative activity against uterine fibroids (UFs). It definitively causes suppression of ovulation and inhibition of proliferation of endometrial, myometrial and UF cells. Purpose: This review aims to summarize current knowledge on VPR from all studies, including clinical trials, conducted to date and to contextualize the potential role of VPR in future medical regimens for the treatment of UFs. Methods: We performed a literature search in PubMed US National Library of Medicine and Google Scholar databases. Both databases were extensively searched for all original and review articles/book chapters as well as congress abstracts published in English until July 2019. The use of VPR for UF therapy was identified by using the keywords: "uterine fibroids" and "vilaprisan". Results: In phase I and II clinical trials, VPR was shown to be effective in ameliorating UF-related clinical symptoms, especially abnormal or excessive uterine bleeding and in shrinking UFs. The tolerability of VPR is roughly similar to that of ulipristal acetate (UPA) and it tends to be more favorable than that of GnRH-agonists. Conclusion: Presently, all trials examining the utility of VPR for the treatment of UF are halted; likely, due to the recent reported cases of hepato-toxicity with UPA, in addition to non reassuring toxicology results from pre-clinical long-term testing on rodents, carried out in parallel with late stage testing on humans. An accurate summary of robust data related to the safety of VPR is urgently needed to draw definitive conclusions on future clinical development of this drug for UF therapy.