European Commission approves Esmya® Type II variation, allowing a repeated course of 3-month treatment for uterine fibroids

European Commission approves Esmya® Type II variation, allowing a repeated course of 3-month treatment for uterine fibroids
January 27, 2013 Irene Tamayo

Budapest, Hungary, 27 January 2013: Gedeon Richter Plc. (“Richter”) announces that Esmya® 5 mg tablets (ulipristal acetate) is now licensed for up to 2 intermittent courses of 3-month treatment for uterine fibroids in the European Union.

The European Commission (EC) has approved the Type II variation to amend Esmya® 5 mg tablets (ulipristal acetate) product information to allow one repeated course of 3-month pre-operative treatment in all countries of the European Union. This decision follows the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) issued in November 2013.

The EC’s approval was based on the results of the PEARL III study and its extension. The studies evaluated the efficacy and safety of repeated intermittent 3-month treatment courses of ulipristal acetate in subjects with uterine fibroids and heavy uterine bleeding. The study results showed that one repeated course of ulipristal acetate delivers continued efficacy for women (Amenorrhea rates were 79.5% and 88.5% for the women after the first and second treatment courses respectively. Median percentage change from screening in fibroid volume reduction were -49.9% and -63.2% after the first and second treatment courses respectively). The positive data from the PEARL III studies were presented at the 10th Congress of the European Society of Gynecology on 18 September 2013.

“We are pleased with this significant step forward for Esmya®, as it means more choice for physicians managing moderate-to-severe symptoms caused by fibroids,” said Erik Bogsch, Managing Director of Gedeon Richter Plc. “We will now be working with local regulatory agencies to communicate the implications of this label extension to physicians in Europe.”

“Esmya® delivers prolonged and continuous efficacy for the widest range of symptoms caused by uterine fibroids,” says Professor Jacques Donnez, who led the PEARL I, II and III studies. “Extending its license increases the pre-operative treatment options open to women who experience this difficult condition and could mean they are spared symptoms for up to one year.”

The full Esmya® 5 mg tablets product information containing the revised SmPC is publicly available in the EC Community Register and available online at www.ema.europa.eu/ema

About uterine fibroids
Uterine fibroids are the most common benign, solid tumours of the female genital tract, affecting between 20 and 40% of women of reproductive age.¹ The condition is characterized by multiple symptoms that include excessive uterine bleeding, anaemia, pain, frequent urination or incontinence, and infertility ²– all of which can compromise quality of life considerably.³ It is estimated that about 300,000 surgical procedures are performed annually in the EU for uterine fibroids, including approximately 230,000 hysterectomies. Gonadotrophin-releasing hormone (GnRH) agonists are also approved as pre-operative treatment for uterine fibroids but their use has been relatively limited due to side effects resulting from the suppression of oestrogen to castration levels (hot flashes, depression, mood swings, loss of libido, vaginitis and loss of bone mineral density).⁴


About Esmya®
 – all of which can compromise quality of life considerably.³ It is estimated that about 300,000 surgical procedures are performed annually in the EU for uterine fibroids, including approximately 230,000 hysterectomies. Gonadotrophin-releasing hormone (GnRH) agonists are also approved as pre-operative treatment for uterine fibroids but their use has been relatively limited due to side effects resulting from the suppression of oestrogen to castration levels (hot flashes, depression, mood swings, loss of libido, vaginitis and loss of bone mineral density).⁴

Esmya® 5 mg tablets containing ulipristal acetate, a new chemical entity, is a first-in-class, orally active, selective progesterone receptor modulator which reversibly blocks the progesterone receptors in target tissues.⁵ As published in the New England Journal of Medicine, the 12 weeks once-a-day oral therapy (vs. injectable GnRH agonist) is effective to stop uterine bleeding, correct anaemia and shrink volume while preparing for surgery.⁶ Thus, it improves quality of life and has fewer castration side effects compared to GnRH agonists.

Esmya® is indicated for pre-operative treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The treatment consists of one tablet of 5 mg to be taken orally once daily for up to 3 months. This 3-month treatment course can be repeated once.

About the study
PEARL III and its extension were long-term, open-label, phase III trials of ulipristal acetate 10 mg, which were double-blinded and placebo-controlled towards the administration of progestin after the end of each ulipristal acetate treatment course.

PEARL III study recruited 209 patients and investigated the efficacy and safety of a single 3-month open-label treatment with ulipristal acetate 10 mg, followed by a randomised, double-blind, placebo-controlled period of 10 days treatment with the progestin, norethisterone acetate, in subjects with uterine fibroids and heavy uterine bleeding. Results are under publication.

At the end of the PEARL III study, patients had the option to continue ulipristal acetate 10 mg treatment in the extension study. This comprised three additional courses of 3-month open-label ulipristal acetate 10 mg treatment, each followed by ten days of double-blind treatment with norethisterone acetate or placebo and then a drug-free period of no treatment prior to the next course. A total of 132 patients opted to continue medical therapy in the extension study. Pearl III extension assessed the efficacy and safety of repeated courses of ulipristal acetate 10 mg on uterine bleeding, myoma size, pain and quality of life. Results are under publication.

It is expected that similarly to the 10 mg dose, the efficacy of the 5 mg dose in the first treatment course will be maintained in the second treatment course.

About Gedeon Richter Plc.
Headquartered in Hungary, Gedeon Richter Plc. is an innovation-driven specialty pharmaceutical multinational company well established in Central Eastern Europe and with an expanding presence in Western Europe in the field of gynaecology. Richter’s consolidated sales was approximately EUR 1.1 billion (USD 1.5 billion) while its market capitalization amounted to EUR 2.3 billion (USD 3.1 billion) in 2012. The product portfolio of the Company covers almost all important therapeutic areas, including gynaecology, central nervous system and cardiovascular. The Company has the largest R&D unit in Central Eastern Europe. Original research activity focuses on CNS disorders with main clinical targets being schizophrenia, anxiety, chronic pain and depression. With its widely acknowledged steroid chemistry expertise Richter is also a significant player in the female healthcare field worldwide. Richter is also active in the scope of biosimilar product development.

¹Wallach E., et al. Uterine Myomas: An Overview of Development, Clinical Features, and Management. The American College of Obstetricians and Gynaecologists, 2004; 104 (2): 393-406.
²Gupta S., et al. Clinical presentation of fibroids. Best Practice and Research Clinical Obstetrics and Gynaecology. 2008; 22(4): 615-626
³Downes E., et al. The burden of uterine fibroids in five European countries. European Journal of Obstetrics & Gynaecology and Reproductive Biology, 2010; 152(1): 96-102
⁴Lethaby A., et al. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroid (Review). The Cochrane Library, 2007; Issue 1.
⁵Esmya® 5mg Summary of Product Characteristics (SmPC)
⁶Donnez J., et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012;
366:421-32.

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