Treatment with vilaprisan for uterine fibroids shows positive outcomes in study

Vilaprisan 2 mg given daily significantly induced amenorrhea, controlled bleeding and decreased uterine fibroids (UF) size in women with heavy menstrual bleeding (HMB) associated with UF, compared to placebo, according to data from the phase 2b randomized controlled randomized ASTEROID 2 trial.¹

Study results, which were published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, also found the drug well tolerated.

Vilaprisan is an investigational selective progesterone receptor modulator(SPRM) and emerging medical treatment being developed by Bayer HealthCare Pharmaceuticals for UF that targets the progesterone receptor expressed on UF tissue to inhibit cell proliferation and induce apoptosis, thus resulting in reduced UF volume.

The study recruited women (mean age 42.5 years), beginning in June 2015. At baseline, mean menstrual blood loss per 28 days was 214.1 mL and the volume of the three largest UF was 106.2 mL among the 155 women who completed the initial 12-weeks of therapy.

The primary endpoint compared the efficacy of vilaprisan to placebo at 12 weeks, defined as the absence of bleeding/spotting recorded in a bleeding diary. Participants also documented menstrual blood loss per sanitary product.

The three largest UF were identified during screening and documented at each ultrasound.

Complete absence of bleeding/spotting until the end of the 12-week treatment period was achieved by 62.9% of women receiving vilaprisan versus 0.0 % with placebo (P < 0.001).

In addition, the predefined HMB response of <80 mL and >50 % reduction from baseline during the last 28 days of treatment was attained by 95.7 % of women treated with vilaprisan.

Secondary endpoints of the study compared the efficacy of vilaprisan to ulipristal acetate, also a SPRM, which was approved in Europe in 2012 and Canada in 2013 for treating UF, but with some reports of serious liver injury.

Overall, 55.4% of women treated with ulipristal acetate 5 mg noticed an absence of bleeding/spotting and 86.5% achieved the predefined HMB response.

Vilaprisan and ulipristal acetate treatment reduced the sum of the volume of the three largest UF, as measured by magnetic resonance imaging (MRI), by 29.9 % and 23.8 %, respectively, in contrast to an increase of 6.3 % in the placebo group.

No safety concerns were noted for any of the treatments.

Results essentially mirror those of the phase 2b ASTEROID 1 trial.

The authors noted that most pivotal trials investigating UF treatment typically use either ultrasound or MRI to measure UF volume, whereas ASTEROID 2 uses both modalities. “The observed differences between the two methods indicate that studies using only ultrasound should be interpreted with caution and highlight MRI as a more precise method in the diagnosis and assessment of women with UF,” they wrote.

Study data indicates that treatment with vilaprisan can achieve higher efficacy at a lower dose than ulipristal acetate, perhaps due to optimization of the molecular structure of vilaprisan, which was developed to maximize specificity for the progesterone receptor, while eliminating structural elements that could induce undesirable liver effects.

Unlike other compounds containing structural motifs known to impact liver function, vilaprisan has a metabolic elimination pathway involving CYP3A, which should result in a favorable hepatic safety profile.

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Reference

1. Gemzell-Danielsson K, Heikinheimo O, Zatik J, et al. Efficacy and safety of vilaprisan in women with uterine fibroids: data from the phase 2b randomized controlled trial ASTEROID 2. Eur J Obstet Gynecol Reprod Biol. 2020 Sep;252:7-14. doi:1016/j.ejogrb.2020.05.043