Successes and failures of uterine leiomyoma drug discovery

Abstract

To-date, the only cure for symptomatic uterine fibroids (UFs) is surgical intervention. However, surgery may eliminate the hope of future pregnancies; moreover, the intrinsic risks of surgery make it a less favorable to women with UFs. Because of this, conservative medical therapies have become an attractive and prior option for those women. Leuprolide acetate (LA), a gonadotropin-releasing hormone (GnRH) agonist, is the only pharmacological agent currently approved for the short-term and pre-operative management of symptomatic UFs in the USA. Areas covered: This systematic review covers the successes and failures of prominent drugs that have been researched for UFs in the past and agents that have shown promise in recent clinical trials. The most recent clinical trials and advances in drug therapy are presented in a comprehensive overview outlining the direction UF drug discovery is heading. Expert opinion: Experts in the field are already on the forefront leading the responsibility to uncover potential drugs as long term fertility friendly viable options for non-invasive treatment/prevention of UFs. Indeed, a shift in the UF management is expected in the future.

Uterine fibroid therapy: the pharmacokinetic considerations

“…Therefore, current treatments aim to suppress or modulate these ovarian sex hormones [1]. Herein we will focus on the most commonly used treatment options, other possible treatment options include aromatase inhibitors, oral contraceptives, Levonorgestrel-releasing intrauterine system, Selective estrogen receptor modulators, localized treatments (gene therapy and collagenase), and alternative medicine (green tea and Vitamin D) can be found in more details in literature [1,3].…”

“…In the past recent years, much interest has emerged around this family members and have been investigated for UF treatment including the forefront Ulipristal acetate (UPA), Vilaprisan, Asoprisnil, and Telapristone (Proellex). The last two were suspended in phase III trials due to abnormal changes in the endometrial lining of patients' uteri and significant elevation of liver enzymes respectively, UPA is approved in Europe and Canada as long-term treatment (up to four treatment courses of 3 months, separated by a drug-free period until the start of the second menstruation following the end of the previous treatment course), it is currently under FDA review in United states [3,7]. Vilaprisan is currently in many Phase 3 clinical studies.…”

“…Yet, many factors halt that preference including, its invasive nature as well as uterus and consequently fertility deprivation [1,2]. In regard to alternatives like pharmacological treatment, unfortunately, majority of the current therapies offer inadequate or short-term control of symptoms and cannot be used for long term because of safety concerns [3]. In this editorial we will glimpse the important medical treatment options for UF, either approved or in the pipeline, with emphasis on their pharmacokinetic (PK) features that certainly can shape the future of UF treatment development.…”

The effect of high-intensity focused ultrasound guided by magnetic resonance therapy on obstetrical outcomes in patients with uterine fibroids – experiences from the main Polish center and a review of current data

“…Another topic to be discussed elsewhere covers several drugs with proven efficacy in the treatment of UFs, including ulipristal acetate (UPA), GnRH analogs [13,24] and others [25][26][27]. The disadvantages of available drugs registered in UF therapy are relatively high price, average efficacy and, often, difficult accessibility.…”

“…None of the available drugs may also be used to prevent the formation of those tumors [21,28]. To date, none of the available hormonally active drugs has been classified for long-term treatment due to side effects accompanying such therapies [19,24,29].…”