Vilaprisan for treating uterine fibroids

Abstract

The medical strategy to antagonize myoma size and related-symptoms is to reduce estrogen and progesterone activity on myomas. This can be obtained with the GnRH agonist (GnRHa) or with compounds that antagonize progesterone stimulatory activity on myomas. Selective progesterone receptor modulators (SPRMs) bind progesterone receptor (PR), leading to both agonist and antagonist effects. The result of SPRMs's action is tissue-specific and it depends on the particular affinity and strength of each SPRM. Area covered: Ulipristal acetate (UPA) is the first SPRM registered for myoma treatment. UPA reduces heavy uterine bleeding within 7 days from the onset of treatment, whereas a longer time is required with GnRHa treatment. Vilaprisan is a novel powerful SPRM. Phase I and II studies give encouraging results on the efficacy of vilaprisan at different doses. Like other SPRMs, vilaprisan induces benign changes of endometrium (PR modulator-associated endometrial changes, PAECs). These disappear as treatment is discontinued. Unlike GnRHa treatment, neither UPA nor vilaprisan induce hypoestrogenism and associated symptoms. Phase III studies are ongoing to confirm efficacy and safety of vilaprisan in long-term treatment of symptomatic fibroids. Expert opinion: It is fundamental to underline the rapidity of action (only 3 days) in the control of myoma-related bleeding.

Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids

“…The alkaline hematin method was used to quantify all bleeding end points. [3][4][5][33][34][35][36][37][38][39] The present data inform the efficacy and safety of this treatment through 6 months; the 6-month extension trial (up to 12 months of treatment) was conducted to provide more information on longer-term benefits and risks of elagolix with add-back therapy, as was previously shown in extension studies of elagolix in women with endometriosis-associated pain. 40 Since the trials were designed primarily to compare elagolix plus add-back therapy with placebo and prespecified a comparison of the two elagolix groups only with respect to bone mineral density, we cannot make conclusions regarding elagolix with add-back therapy as compared with elagolix alone with respect to the effects on other outcomes.…”

Uterine fibroid therapy: the pharmacokinetic considerations

“…Progesterone concentration was persistently low in most of participants during treatment with 1 mg [13]. Vilaprisan peak plasma concentration was achieved 1-2 h after oral dose, and the half-life is about 35 h which permit once daily administration with linear PK in the expected therapeutic dose range [12,13]. Vilaprisan chemical structure, as well as Asoprisnil, is slightly different from UPA in lacking the N-dimethyl-amino-phenyl group in the position 11 of the steroid.…”

“…A transient elevation in liver enzymes was found in six subjects, regardless of the study drug dose used, however, values returned to normal range during ongoing treatment in all cases [12]. Table 1 summarizes the PK features of the aforementioned anti-UF medications.…”

“…Vilaprisan is a novel highly potent SPRM currently under evaluation for long-term treatment of symptomatic UFs [12]. Phase I studies showed that daily Vilaprisan doses of 0.5 mg or higher were able to reduce mean maximum serum concentrations of LH and FSH and 1 mg doses or higher decreased mean maximum estradiol concentrations.…”

Atypical uterine myoma in young women: diagnostics, treatment, rehabilitation

“…Миома матки возникает из гладкомышечной клетки, и ее развитие зависит от гормональных изменений в женском организме, где центральная роль принадлежит эстрогену, прогестерону и их рецепторам [1][2][3][4][5][6]. Симптомная миома матки -одна из основных причин обращения к гинекологу [7][8][9] и проведения радикальных операций [10,11], которые нежелательны в любом возрасте, особенно в молодом, когда не реализована репродуктивная функция [12,13].…”