ObsEva SA Announces the Completion of a Phase 1 PK/PD Clinical Trial Evaluating Different Doses of OBE2109 and Add-Back Therapy
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ObsEva SA /
ObsEva SA Announces the Completion of a Phase 1 PK/PD Clinical Trial Evaluating
Different Doses of OBE2109 and Add-Back Therapy
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The issuer is solely responsible for the content of this announcement.
- OBE2109 is a GnRH receptor antagonist currently in development as both a
stand-alone treatment and with add-back therapy designed to address the needs of
endometriosis and uterine fibroid patients -
Geneva, Switzerland and Boston, MA - 07 June 2017 - ObsEva SA (Nasdaq: OBSV), a
Swiss biopharmaceutical company focused on the development and commercialization
of novel therapeutics for serious conditions that compromise a woman's
reproductive health and pregnancy, today announced the completion of a Phase 1
clinical trial aimed at evaluating the PK/PD relationship of OBE2109 combined
with different doses of add-back therapy.
OBE2109 is a novel, oral GnRH receptor antagonist that is currently in a Phase
2b clinical trial for the treatment of pain associated with endometriosis (EM)
and in Phase 3 clinical trials for the treatment of heavy menstrual bleeding
(HMB) associated with uterine fibroids (UF) in pre-menopausal women. Although
estrogen (E2) suppression is a well-validated strategy for alleviating symptoms
of UF and EM, therapeutic benefit can be compromised by hypo-estrogenic effects,
principally bone mineral density (BMD) loss. This often necessitates
administration of add-back therapy (ABT) to patients, which delivers
estrogen/progestogens to counteract the deleterious effects of BMD. The ongoing
OBE2109 development program is investigating two complementary approaches to
achieving what ObsEva believes is the optimal estrogen level to find a balance
between efficacy and side effects. The first approach is to use a "low" dose of
OBE2109 that targets an E2 range of 20 to 60 pg/mL, without the addition of add-
back therapy. The second approach targets maximal E2 suppression with a "high"
dose of OBE2109, combined with add-back therapy to bring exogenous E2 back to
the desired level that is intended to aid BMD safety.
"We are very pleased by the results of this important PK/PD study in which we
observed in Caucasian subjects the rapid onset and effectiveness of OBE2109 to
reduce E2 levels that was previously reported in Japanese subjects," said Ernest
Loumaye, MD, PhD, OB&GYN, CEO and Co-Founder of ObsEva. "We believe there are
several important observations from this study that support our ongoing
development strategy for OBE2109 as a treatment for EM and UF. First, the
OBE2109 dosages of 100 mg and 200 mg being tested in our ongoing PRIMROSE 1 and
PRIMROSE 2 Phase 3 clinical trials, as well as add-back therapy of 1mg/0.5
E2/norethindrone acetate (NETA), appear to be doses that balance the intended
therapeutic effect with deleterious side effects. Second, as demonstrated by
the median E2 level of 18 pg/mL following six weeks of dosing with 100 mg of
OBE2109, upwards of 50% of patients may not require add-back therapy. And
third, the addition of add-back therapy intended to counteract BMD reduction
appears to significantly moderate the potential benefit of GnRH antagonism, in
terms of bleeding control as measured by rates of amenorrhea and spotting.
Therefore, we continue to believe that development of two regimens of
administration for OBE2109 (with and without ABT) may best address the needs of
the EM and UF populations."
The present Phase 1 clinical trial reported herein aimed to evaluate the
pharmacodynamics, safety, tolerability and pharmacokinetics of the oral GnRH
receptor antagonist OBE2109 alone or co-administered with E2/NETA add-back
therapy. This was a prospective, randomized, parallel group study involving 76
healthy, Caucasian women of child-bearing potential. Subjects were randomized to
one of five arms for a period of six weeks to receive either 100 mg of OBE2109
alone or with one of two ABT doses (E2/NETA: 0.5mg/0.1mg or 1mg/0.5mg), or 200
mg of OBE2109 alone or with the standard dose of ABT (E2/NETA: 1mg/0.5mg).
ObsEva observed that OBE2109 at 100 mg and 200 mg doses rapidly reduced E2 to
levels that are expected to treat symptoms of UF and EM (see Table 1 below). The
marked E2 reduction seen with standalone dosing supports the need for ABT to
minimize BMD loss in the 200 mg group, and potentially in some subjects treated
with 100 mg. The addition of ABT doses in the study to subjects treated with
100 mg and 200 mg of OBE2109 restored E2 levels to the target range that ObsEva
believes would minimize BMD loss. As for the other metric in this clinical
trial, the bleeding pattern during the final four weeks of treatment, results
were as expected; the vast majority of patients achieved amenorrhea when treated
with OBE2109 alone. Notably, the majority of patients in each treatment arm
achieved a status of either "amenorrhea," or bleeding characterized as "spotting
only," which ObsEva believes demonstrates the benefit of combined OBE2109/ABT
(see Table 2 below). However, the rates of bleeding control were lower in
treatment arms that included ABT.
Table 1: Median (IQR: 25 - 75%) E2 level after week 1 and 6 of treatment
+------------------+---------+-----------+----------+-------+----------+
|OBE2109 daily dose|100 mg |100 mg |100 mg |200 mg | 200 mg |
| |(n=14) |(n=14) |(n=15) |(n=14) | (n=15) |
+------------------+---------+-----------+----------+-------+----------+
| Add-Back E2/NETA | |0.5mg/0.1mg|1mg/0.5mg | |1mg/0.5mg |
+------------------+---------+-----------+----------+-------+----------+
|E2 Week 1 [pg/mL] |12 (9-18)|25 (18-30) |35 (26-45)|5 (4-7)|27 (22-38)|
+------------------+---------+-----------+----------+-------+----------+
|E2 Week 6 [pg/mL] |18 (9-27)|40 (31-50) |34 (26-47)|3 (2-3)|25 (21-34)|
+------------------+---------+-----------+----------+-------+----------+
Table 2: Bleeding pattern during the last four weeks of treatment
+--------------------------+------+-----------+---------+------+---------+
| OBE2109 daily dose |100 mg| 100 mg | 100 mg |200 mg| 200 mg |
| |(n=14)| (n=14) | (n=15) |(n=15)| (n=15) |
+--------------------------+------+-----------+---------+------+---------+
| Add-Back E2/NETA | |0.5mg/0.1mg|1mg/0.5mg| |1mg/0.5mg|
+--------------------------+------+-----------+---------+------+---------+
| Amenorrhea | 86% | 21% | 53% | 87% | 33% |
| (no bleeding) | | | | | |
+--------------------------+------+-----------+---------+------+---------+
|Amenorrhea + spotting only| 93% | 57% | 93% | 100% | 60% |
+--------------------------+------+-----------+---------+------+---------+
From a safety standpoint, all regimens were well-tolerated and no safety signal
emerged. OBE2109 has now been dosed in more than seven hundred (700) women.
ObsEva plans to submit detailed results for presentation at a future scientific
conference.
About Uterine Fibroids
Uterine fibroids are common non-cancerous tumors that grow within the muscular
wall of the uterus. They can vary in size and number and when symptomatic, are
most often accompanied by heavy menstrual bleeding, anemia, abdominal pressure
and pain, bloating, increased urinary frequency and reproductive dysfunction.
Uterine fibroids are associated with an increased risk of pregnancy
complications such as infertility, miscarriage, placental abruption and early
onset of labor. According to a study published in the American Journal of
Obstetrics & Gynecology in 2003, uterine fibroids affect an estimated 20 to 40
percent of women over the age of 30 in the United States based on clinical cases
and women who undergo treatment.
For the millions of women with symptomatic uterine fibroids seeking treatment
options, selection is driven by symptom severity, the woman's age, and her
desire to have children now or in the future. While medical, surgical and
minimally invasive treatments are available, the standard of care for
symptomatic uterine fibroids is a hysterectomy or, in women who wish to preserve
their fertility, surgical removal of the fibroid(s).
About Endometriosis
Endometriosis is a disease in which the endometrium (tissue lining the inside of
the uterus) grows outside of the uterus, where it induces a chronic inflammatory
reaction in the abdomen that may result in scar tissue. It is primarily found on
the pelvic peritoneum, on the ovaries, in the rectovaginal septum, on the
bladder and in the bowels. The most common symptom of endometriosis is pelvic
pain, which often correlates to the menstrual cycle. Patients may also
experience painful ovulation, pain during or after sexual intercourse, heavy
bleeding, chronic pelvic pain, fatigue and infertility. For many, endometriosis
pain can be so severe and debilitating that it impacts do day-to-day activities
and has a negative effect on general physical, mental and social well-being.
Endometriosis treatments aim first to alleviate pain, then to remove or decrease
the size and number of endometrial lesions, and possibly improve fertility. Oral
contraceptives, progestins and NSAIDs are generally first-line treatments for
women experiencing pain. Following the failure of first-line therapies, current
treatment options are limited to intra-muscular or subcutaneous GnRH agonist
injections, GnRH agonists nasal spray pumps or surgery (including hysterectomy)
for the most symptomatic cases.
The World Endometriosis Research Foundation's EndoCost study estimated the
aggregate annual cost of endometriosis to be approximately $80 billion in the
United States and approximately $60 billion in Germany, the UK, France and Italy
in 2012 based on current exchange rates.
About OBE2109 and GnRH
OBE2109 is a novel, orally administered GnRH receptor antagonist with a
potentially best-in-class profile in late-stage clinical development for the
treatment of pain associated with endometriosis and heavy menstrual bleeding
associated with uterine fibroids. OBE2109 acts by binding to and blocking the
GnRH receptor in the pituitary gland, ultimately reducing estrogen production by
the ovaries. Through previously reported results from this class of drugs and
sophisticated pharmacological modelling, it has been established that
maintaining estradiol within a specific target range provides the optimal
balance between reducing symptoms while mitigating bone density loss associated
with excessive estradiol suppression. ObsEva licensed OBE2109 from Kissei in
late 2015 and retains worldwide commercial rights, excluding Asia, for OBE2109.
About Kissei
Kissei is a Japanese pharmaceutical company with approximately 70 years of
history, specialized in the field of urology, kidney - dialysis and Unmet
Medical Needs. Silodosin is a Kissei product for the treatment of the signs and
symptoms of benign prostatic hyperplasia which is sold worldwide through its
licensees. KLH-2109/OBE2109 is a new chemical entity discovered by Kissei R&D.
About ObsEva
ObsEva is a clinical-stage biopharmaceutical company focused on the clinical
development and commercialization of novel therapeutics for serious conditions
that compromise a woman's reproductive health and pregnancy. Through strategic
in-licensing and disciplined drug development, ObsEva has established a late-
stage clinical pipeline with development programs focused on treating
endometriosis, uterine fibroids, preterm labor and improving ART outcomes.
ObsEva is listed on The NASDAQ Global Select Market and is trading under the
ticker symbol "OBSV". For more information, please visit www.ObsEva.com.
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical
facts may constitute forward-looking statements as that term is defined in the
Private Securities Litigation Reform Act of 1995. These statements may be
identified by words such as "believe", "expect", "may", "plan," "potential,"
"will," and similar expressions, and are based on ObsEva's current beliefs and
expectations. These forward-looking statements include expectations regarding
the clinical development of OBE2109, including its safety, tolerability and
potential for efficacy. These statements involve risks and uncertainties that
could cause actual results to differ materially from those reflected in such
statements. Risks and uncertainties that may cause actual results to differ
materially include uncertainties inherent in the conduct of clinical trials and
related interactions with regulatory bodies, ObsEva's reliance on third parties
over which it may not always have full control, and other risks and
uncertainties that are described in the Risk Factors section of ObsEva's Annual
Report on Form 20-F for the year ended December 31, 2016, and other filings
ObsEva makes with the SEC from time to time. These documents are available on
the Investors page of ObsEva's website at http://www.obseva.com. Any forward-
looking statements speak only as of the date of this press release and are based
on information available to ObsEva as of the date of this release, and ObsEva
assumes no obligation to, and does not intend to, update any forward-looking
statements, whether as a result of new information, future events or otherwise.
###
Media Contact:
Liz Bryan
Spectrum Science
lbryan(at)spectrumscience.com
202-955-6222 x2526
Company Contact:
CEO Office Contact
Delphine Renaud
delphine.renaud(at)obseva.ch
+41 22 552 1550
Investor Contact
Mario Corso
Senior Director, Investor Relations
mario.corso(at)obseva.com
781-366-5726
Press release:
http://hugin.info/157613/R/2110945/802442.pdf
This announcement is distributed by Nasdaq Corporate Solutions on behalf of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: ObsEva SA via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 07.06.2017 - 13:00 Uhr
Sprache: Deutsch
News-ID 546788
Anzahl Zeichen: 16021
contact information:
Town:
Plan-les-Ouates
Kategorie:
Business News
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