Final results of ObsEva SA Phase 2b EDELWEISS trial of Linzagolix
show sustained efficacy and Bone Mineral Density safety, for the
treatment of endometriosis-associated pain
- Linzagolix overall efficacy and safety maintained or
improved at week 24
- Linzagolix 75mg once daily showed no clinically
significant impact on Bone Mineral Density (BMD), supporting
further development with no need for add back therapy
(ABT)
- Linzagolix 200mg once daily results support further
development with low dose add back therapy
(ABT)
- Initiation of Phase 3 endometriosis trials expected in
early 2019
Geneva, Switzerland and Boston, MA
– September 28, 2018- ObsEva SA (NASDAQ: OBSV / SIX:
OBSN), a Swiss clinical-stage 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 additional positive results from the
EDELWEISS clinical trial of its oral GnRH receptor antagonist,
linzagolix, for the treatment of endometriosis-associated
pain.
In the EDELWEISS trial, hallmark pain symptoms
of endometriosis, dysmenorrhea (DYS) and non-menstrual pelvic pain
(NMPP), showed sustained reduction or further improvement after 24
weeks of treatment, as compared to the positive 12-week results
that were announced in June 2018. Sustained efficacy was also seen
in additional endpoints such as dyspareunia and dyschezia, as well
as in the assessments of patient well-being, most notably the
Patient Global Impression of Change (PGIC) and Endometriosis Health
Profile-30 (EHP-30) questionnaire.
The main pain efficacy endpoints of the
EDELWEISS clinical trial were reported as a responder analysis,
with responses defined as a reduction of at least 30% in pain,
recorded daily via electronic diary using a verbal rating scale
(VRS) of 0 (no pain) through 3 (severe pain).
“We are very pleased with these favorable
results that further demonstrate the differentiated therapeutic
potential of linzagolix for alleviating the severe, painful and
chronic symptoms of endometriosis. These data strongly validate
ObsEva’s development strategy for linzagolix as a potential best in
class oral GnRH antagonist,” said Dr. Loumaye, co-founder and Chief
Executive Officer of ObsEva.
Study Top-Line Results
Overall pelvic pain responder analysis @
week 12 and week 24 (0-3 VRS)
Dose (once daily) n=FAS* |
Placebo (53) |
50mg (49) |
75mg (114) |
100mg (51) |
200mg (56) |
Responder Rate @ Week 12 |
34.5 |
% |
49.4 |
% |
61.5 |
% |
56.4 |
% |
56.3 |
% |
P-Value vs Placebo @ Week 12 |
— |
|
0.155 |
|
0.003 |
|
0.039 |
|
0.034 |
|
Responder Rate @ Week 24 |
N/A |
52.5 |
% |
70.8%** |
66.7 |
% |
77.3 |
% |
*FAS = Full Analysis Set**sub-group randomized
to fixed dose 75mg for 24 weeks (n=56)
Non-menstrual pelvic pain responder
analysis @ week 12 and week 24 (0-3 VRS)
Dose (once daily) n=FAS* |
Placebo (n=53) |
50mg (49) |
75mg (114) |
100mg (51) |
200mg (56) |
Responder Rate @ Week 12 |
37.1 |
% |
46.2 |
% |
58.5 |
% |
61.5 |
% |
47.7 |
% |
P-Value vs Placebo@ Week 12 |
— |
|
0.380 |
|
0.017 |
|
0.022 |
|
0.297 |
|
Responder Rate @ Week 24 |
N/A |
50.0 |
% |
72.9%** |
64.1 |
% |
72.7 |
% |
*FAS = Full Analysis Set**sub-group randomized
to fixed dose 75mg for 24 weeks (n=56)
Dysmenorrhea pain responder analysis @
week 12 and week 24 (0-3 VRS)
Dose (once daily) n FAS* |
Placebo (53) |
50mg (49) |
75mg (114) |
100mg (51) |
200mg (56) |
Responder Rate @ Week 12 |
28.5 |
% |
43.3 |
% |
68.2 |
% |
68.6 |
% |
78.9 |
% |
P-Value vs Placebo @ Week 12 |
— |
|
0.141 |
|
<0.001 |
<0.001 |
<0.001 |
Responder Rate @ Week 24 |
N/A |
47.5 |
% |
58.3%** |
82.1 |
% |
84.1 |
% |
*FAS = Full Analysis Set**sub-group randomized
to fixed dose 75mg for 24 weeks (n=56)
Overall linzagolix safety and tolerability were
shown not to be different from placebo, except as expected for a
dose-dependent increase in hot flushes (placebo at week 12: 10.9%
of subjects reporting at least one hot flush; linzagolix 75mg at
week 24: 19.0%; linzagolix 200mg at week 24: 45.6%).
In addition, changes from baseline to week 24 in
BMD, as measured by dual-energy x-ray absorptiometry (DXA) scan are
reported in the table below. Partial estradiol (E2) suppression
with linzagolix 75mg allows the lower boundary of the confidence
interval of BMD reduction from baseline to be comfortably better
than -2.2%, the cut-off limit for clinically significant BMD loss,
while achieving improvement of the conditions in the majority of
patients. As expected, full E2 suppression with linzagolix 200mg
was observed to reduce lumbar spine BMD by more than 2.0%, which we
believe will indicate the need for a low dose ABT when used beyond
6 months.
Mean Percent BMD change from baseline to
week 24 (mean, 95% CI, p value)
Dose (once daily) |
50mg |
75mg |
100mg |
200mg |
Femoral Neck |
-0.749% (-1.45, -0.05) 0.037 |
-0.334% (-1.08, 0.42) 0.375 |
-0.986% (-1.88, -0.10) 0.031 |
-1.992% (-2.88, -1.10) <0.001 |
Total Hip |
0.378% (-0.15, 0.90) 0.154 |
-0.457% (-1.06, 0.15) 0.136 |
-0.278% (-0.88, 0.33) 0.359 |
-1.690% (-2.45, -0.93) <0.001 |
Lumbar Spine |
0.137% (-0.83, 1.11) 0.777 |
-0.798% (-1.57, -0.03) 0.042 |
-1.365% (-2.14, -0.59) <0.001 |
-2.602% (-3.56, -1.65) <0.001 |
Overall, we believe these data strongly support
the planned development of a 75mg once daily dose (without ABT),
and a 200mg once daily dose in combination with low dose ABT.
Offering dual therapeutic options, is the cornerstone of ObsEva’s
strategy to address the needs of the large and diverse
endometriosis patient population. In that context, we believe that
if successful in Phase 3 trials and approved, the 75mg dose has the
potential to become first line therapy (i.e. without ABT), as ABT
may change the risk benefit ratio of the treatment. We believe this
is further supported by the preference for dose flexibility among
U.S. gynecologists.
ObsEva plans to provide additional details from
the EDELWEISS trial at a later date, including presentation at a
future medical conference. Following End-of-Phase 2
regulatory discussions, expected later this year, ObsEva intends to
initiate the Phase 3 program of linzagolix for the treatment of
endometriosis-associated pain in early 2019.
About Endometriosis
The World Endometriosis Research Foundation
estimates that endometriosis affects one in ten women during their
reproductive years, representing approximately 176 million women
worldwide between the ages of 15 and 49. 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 U.K., France
and Italy in 2012 based on current exchange rates.
Endometriosis is a disease in which the
endometrium (tissue lining the inside of the uterus) is found
outside the uterus, where it induces a chronic inflammatory
reaction 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 bowel. 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 (dyspareunia), dyschezia (difficult or
painful defecation), heavy bleeding, fatigue and infertility.
Endometriosis pain can be so severe and debilitating that it
affects day-to-day activities and has a negative impact 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.
About LINZAGOLIX (OBE2109)
Linzagolix 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. Linzagolix acts by binding to and
blocking the GnRH receptor in the pituitary gland, ultimately
reducing estrogen production by the ovaries. Given reported results
from this class of drugs and sophisticated pharmacological
modelling, linzagolix is being developed to potentially provide two
regimens of administration, one targeting partial suppression of
estradiol that will not necessitate add-back therapy (ABT) in the
majority of patients (a potential preferred, first line
treatment), and one targeting full or near full estradiol
suppression that would require the administration of a low ABT,
with the goal of providing appropriate treatment to the broadest
possible proportion of the endometriosis and uterine fibroid
patient populations. ObsEva licensed OBE2109 from Kissei in
2015 and retains worldwide rights, excluding Asia.
To date, more than 1,500 subjects have been
exposed to linzagolix in clinical trials and linzagolix has been
generally well tolerated.
About the EDELWEISS trial
EDELWEISS is a Phase 2b, randomized, double
blind, placebo controlled clinical trial designed to evaluate the
safety and efficacy of multiple doses of linzagolix in 327 women
with moderate-to-severe endometriosis-associated pain.
Patients were randomized to receive either an oral once daily
dose of linzagolix (50mg, 75mg, 100mg or 200mg) or placebo for up
12 weeks.
Subsequently, patients continued their treatment
as initially randomized up to 24 weeks but subjects on placebo
received 100mg of linzagolix and half of the subjects on 75 mg were
titrated according to their estradiol levels to either 50mg, 75mg
or 100mg of linzagolix.
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/linzagolix is a new chemical entity
discovered by Kissei R&D and currently in development in Japan
by Kissei.
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 IVF outcomes. ObsEva is listed on the
NASDAQ Global Select Market and is trading under the ticker symbol
"OBSV" and on the SIX Swiss Exchange where it is trading under the
ticker symbol “OBSN”. 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 ObsEva’s product candidates, the timing of enrollment in and
data from clinical trials and the results of interactions with
regulatory authorities. 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, clinical
development and related interactions with regulators, 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, 2017, and other filings ObsEva makes
with the SEC. 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.
###
For further information, please
contact:
Media Contact Switzerland and
Europe:Christophe LampsDynamics Groupcla@dynamicsgroup.ch
+41 22 308 6220 Office+41 79 476 26 87 Mobile
Media Contact U.S.:Marion
JanicRooneyPartners LLCmjanic@rooneyco.com+1 212 223 4017 Office+1
646 537 5649 Mobile
CEO Office Contact:Shauna
DillonShauna.dillon@obseva.ch+41 22 552 1550
Investor Contact:Mario
CorsoSenior Director, Investor Relationsmario.corso@obseva.com+1
857 972 9347 Office+1 781 366 5726 Mobile