Geneva, Switzerland – 2 February 2012 – PregLem, the wholly owned subsidiary of Gedeon Richter, announces full results of PEARL I and II studies, published simultaneously in the New England Journal of Medicine (NEJM). The company has recently received positive EMA/CHMP opinion for Esmya® 5 mg (ulipristal acetate) in the pre-operative treatment of uterine fibroids (myomas) and is expecting a marketing authorization by the European Commission early this year.
- Ulipristal acetate controlled bleeding in over 90% of patients.
- Excessive bleeding was controlled significantly more rapidly with ulipristal acetate than with leuprolide acetate.
- Ulipristal acetate significantly reduced fibroid size and for patients who did not undergo surgery, the volume reduction was maintained for at least 6 months after treatment is discontinued.
PEARL I, a randomized, parallel-group, double-blind, placebo-controlled, phase 3 trial showed:
- Uterine bleeding was controlled in 91% of the women receiving ulipristal acetate 5 mg and in 92% of those receiving ulipristal acetate 10 mg, and 19% of those receiving placebo (P<0.001).
- The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate.
- The median changes in total fibroid volume were −21%, −12%, and +3% (P = 0.002 ulipristal acetate 5 mg vs. placebo, and P = 0.006 ulipristal acetate 10 mg vs. placebo).
- As compared with placebo, both doses of ulipristal acetate led to reductions in pain (especially moderate or severe pain), as measured with the Short-Form McGill Pain Questionnaire.
- Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy.
- The rate of the occurrence of any adverse events did not differ significantly among the three groups. Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo.
PEARL II, a double-blind, double-dummy, phase 3 trial comparing ulipristal acetate versus the injectable GnRH agonist (leuprolide acetate) showed:
- Uterine bleeding was controlled in 90% of patients receiving ulipristal acetate 5 mg and in 98% of those receiving ulipristal acetate 10 mg, and in 89% of those receiving leuprolide acetate.
- Excessive bleeding control was demonstrated with statistical significance to be more rapid in patients receiving either ulipristal acetate 5 mg or ulipristal acetate 10 mg, than in those receiving leuprolide acetate.
- Median times to amenorrhea were 7 days for patients receiving ulipristal acetate 5 mg, 5 days for those receiving ulipristal acetate 10 mg, and 21 days for those receiving leuprolide acetate.
- All treatments reduced the volume of the three largest fibroids, with median reductions at week 13 of 36% in the group receiving ulipristal acetate 5 mg, 42% in the group receiving ulipristal acetate 10 mg, and 53% in the group receiving leuprolide acetate.
- For patients who did not undergo hysterectomy or myomectomy, ulipristal acetate showed a more sustained effect on the reduction of fibroids volume during the 6 months follow up without treatment than did leuprolide acetate.
- Moderate-to-severe hot flashes were reported for 11% of patients receiving ulipristal acetate 5 mg, for 10% of those receiving ulipristal acetate 10 mg and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate).
- There were no significant differences between the ulipristal acetate groups and the leuprolide acetate group in the proportion of patients reporting other adverse events or discontinuing treatment because of adverse events.
“These results are good news for women suffering from uterine fibroids” said Prof. Jacques Donnez, lead investigator in PEARL I and II and lead author of the NEJM articles. “Esmya® 5 mg will represent a real new therapeutic option for physicians treating these women.”
About uterine fibroids
Uterine fibroids are the most common benign, solid tumours of the female genital tract, affecting between 20 and 25 percent of women of reproductive age. It is estimated that about 300,000 surgical procedures are performed annually in the EU for uterine fibroids, including approximately 230,000 hysterectomies. The condition is characterized by excessive uterine bleeding, anaemia, pain, frequent urination or incontinence, and infertility. GnRH agonists are the only approved pre-operative treatment for uterine fibroids but their use has been relatively limited due to side effects resulting from the suppression of estrogen to castration levels (hot flashes, depression, mood swings, loss of libido, vaginitis and loss of bone mineral density).
Esmya® 5 mg tablet containing ulipristal acetate, is a first-in-class, orally active, selective progesterone receptor modulator which reversibly blocks the progesterone receptors in target tissues. As published in NEJM, the 12 weeks once-a-day oral therapy (vs. injectable GnRH agonist) is effective to stop uterine bleeding, correct anaemia and shrink fibroid volume. It improves quality of life and has no castration side effects compared to GnRH agonists. There are no data available on treatment with duration longer than 3 months.
About PEARL studies
PEARL I and II (PGL4001’s – a code name for ulipristal acetate) Efficacy Assessment in Reduction of symptoms due to uterine Leiomyomata) are two Phase 3 clinical trials conducted mainly in Europe.
PEARL I, a randomized, parallel-group, double-blind, placebo-controlled, phase 3 trial involved 242 patients. PEARL II, a randomized, parallel-group, double-blind, double-dummy, phase 3 trial comparing ulipristal acetate versus the injectable GnRH agonist (leuprolide acetate) involved 307 patients.
Both pivotal studies included premenopausal women, 18-50 years of age, with symptomatic fibroids, including heavy menstrual bleeding, eligible for hysterectomy. In addition to heavy menstrual bleeding, patients in PEARL I study had to be anaemic and therefore all subjects received concomitant oral administration of iron. The treatment periods of 12 weeks were followed by an end-of- treatment visit at week 13. Subjects still qualifying for surgery underwent hysterectomy, myomectomy, uterine artery embolization or endometrial ablation as determined by the investigator. All subjects were followed for 6 months after the end of treatment.
The primary objectives of PEARL I were to demonstrate superior efficacy of ulipristal acetate versus placebo, to reduce excessive uterine bleeding and to reduce total fibroid volume prior to surgery.
The primary efficacy objective of PEARL II was to demonstrate non- inferior efficacy of ulipristal acetate versus Gonadotropin Releasing Hormone (GnRH)-agonist to reduce, prior to surgery, excessive uterine bleeding caused by uterine fibroids. The co-primary safety objectives were to show a superior side-effect profile for ulipristal acetate versus leuprolide acetate in terms of serum estradiol levels at week 13 and the proportion of patients with moderate-to-severe hot flashes during treatment.
Gedeon Richter Plc. (www.richter.hu) headquartered in Budapest/Hungary, is a major pharmaceutical company in Hungary and one of the largest in Central Eastern Europe, with an expanding direct presence in Western Europe in the field of gynaecology. Richter’s consolidated sales was approximately EUR 1 billion (USD 1.3 billion) while its market capitalization amounted to EUR 2.9 billion (USD 3.8 billion) in 2010. 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.
PregLem Holding SA (www.preglem.com), the wholly owned subsidiary of Richter, is a Swiss speciality biopharmaceutical company, based in Geneva, dedicated to the development and commercialization of a new class of drugs for women’s reproductive health conditions. PregLem has an experienced senior management team, with a proven track record in developing, registering and commercializing reproductive health products.
For further information:
Richter (Budapest, Hungary)
Investors: Katalin Ördög, +36 1 431 5680
PregLem (Geneva, Switzerland)
Media: Delphine Renaud (CEO Office), +41 (0) 22 884 0386