ellaOne® slides kit

http://www.ellaone.com
 Purpose & Warning

• The purpose of this document is to provide a set of slides summarizing all key
information available on ella® / ellaOne®

• This slides kit is aimed to help you to prepare presentations to be used for
internal purposes

• It is your responsibility to make sure that your final presentation will be in

compliance with local applicable regulations
 Outline

• Emergency contraception
1. Physiology
2. History of emergency contraception
3. Contraceptive environment across countries

• ellaOne®/ella®, the new EC generation

4. History / Clinical Development
5. Efficacy and safety in summary
6. Mechanism of action
7. ellaOne® post marketing studies
8. ellaOne® in practice / recommendations
1. PHYSIOLOGY

4
 Female anatomy

Fallopian tube
Uterus

Ovary

Fimbriae
Cervix

Vagina
 Definitions & Functions
 Hormone:
Chemical substance secreted in blood and acting away from its production site.

 Pituitary gland:  Ovary:

The main endocrine gland, called the master gland because
it produces hormones that control other glands and many
body functions. The pituitary consists of the anterior and
posterior pituitary.
– FSH: follicle growth
– LH: ovulation inducer
Female gonad, one of a pair of reproductive glands in women.
The ovaries produce eggs (ova) and female hormones.
– Estrogens: Endometrial growth
– Progesterone: Endometrial differentiation

 Follicle:
Composed of a roughly spherical aggregations of cells which
contains a single oocyte. Follicles are periodically initiated to
grow and develop in cohorts, culminating in ovulation of usually a
single competent oocyte.
 Ovulation:
The release of the ripe egg from the ovary. The egg is
released when the cavity surrounding it (the antral follicle)
breaks open in response to a hormonal signal: LH
peak, about 36 hours before.

Day 1 of menstrual cycle = First day of menses

 The basics of reproductive physiology

The Egg Spermatozoa Ovulation

May remain 12 to 24 hours in the May survive 5 days in women’s

fallopian tube after ovulation (1) (2) reproductive tract (1) (2) Time of ovulation is variable

Only 30% of women ovulate between day

10 & day 17 of the menstrual cycle (3)

1. Wilcox AJ et al. Timing of sexual intercourse in relation to ovulation. N Eng J Med 1995;333:1517-21
2. Trussell J et al. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception 1998;57:363-369
3. Wilcox AJ et al. The timing of the « fertile window » in the menstrual cycle: day specific estimates from a prospective study. BMJ 2000;321:1259-62
 Menstrual Cycle

Follicular phase (1) Ovulation (2) Luteal phase (3)

(Proliferative)
First phase of cycle
Endometrial proliferation due to
rising estrogen levels
(Secretory)
Ovum expulsion in the fallopian tube
Endometrial cells develop secretory
Time may vary considerably: glands. Prepares endometrium for
may occur at an unexpected time implantation
Menstrual cycle - Follicular phase
 Follicular phase: the first “half” of the cycle.
Follicles develop and mature, until a dominant follicle emerges and the rest regress

Graafian follicle

Ovarian cycle

Recruited follicles

Ovarian hormones

UTERUS
Shedding of the
endometrium
 Menstrual cycle - Luteal phase
Following ovulation the remains of the Graafian follicle forms the Corpus luteum (yellow body)
If no pregnancy occurs the corpus luteum degenerates

Corpus luteum

Ovarian cycle

Degeneration

Ovarian hormones
 Menstrual cycle – Follicular Phase
HYPOTHALAMUS

GnRH
ANTERIOR
PITUITARY
Ovulatory peak
Pituitary gonadotropins

FSH release from the pituitary gland

leads to development of follicles

Ovarian cycle

PITUITARY

Ovarian hormones
 Menstrual cycle – Follicular Phase
HYPOTHALAMUS
GnRH
ANTERIOR PITUITARY

Follicles produce estrogen whilst Pituitary gonadotropins

growing. Estrogen and
progesterone provide negative
feedback to hypothalamus.
Ovarian cycle

OVARY

Ovarian hormones

The estrogen causes

proliferation of
endometrium
 Menstrual cycle–LH surge/ovulation

HYPOTHALAMUS
GnRH
ANTERIOR
PITUITARY
Ovulatory peak
Pituitary gonadotropins

Estrogen levels peaking causes

positive feedback to Ovarian cycle
hypothalamus which causes
release of LH

Ovarian hormones
 Menstrual cycle – Luteal phase

Pituitary gonadotropins
Surge-like LH release leads to
ovulation and causes ruptured
follicle to develop into corpus
luteum
Ovarian cycle

Corpus luteum produces

progesterone and estradiol
Ovarian hormones

Progesterone causes
endometrium secretory
differentiation

14
 Menstrual cycle - Menses

Pituitary gonadotropins
The drop in hormone levels
stops the negative feedback on
hypothalamus, which starts
releasing GnRH again
Ovarian cycle

If fertilisation has not occurred

the corpus luteum degenerates
and progesterone and estrogen
levels drop Ovarian hormones

The endometrium starts

degrading and shedding in
response to dropping
hormone levels
 The timing of the fertile window is highly variable…

… Even among women who consider their menstrual cycles as regular (1)

 More than 70% of women are in their fertile window before day 10 or after day 17 of their menstrual cycle (1)

 There is no time in the menstrual cycle when there is no risk of pregnancy following unprotected sexual
intercourse (2)

(1) Wilcox,and al. The timing of “the fertile window” in the menstrual cycle. : day specific estimates from a prospective study.BMJ .2000 Nov 18, 321
(7271):1259 -1262
(2) Faculty of Family Planning and Reproductive health Care.. J Fam Plann Health care. 2006 Apr; 32(2):121-8.
 Probability of conception is higher close to ovulation

 Probability of conception is higher on specific days close to ovulation (1), but very difficult to
determine in real life

 Sexual intercourse is more frequent during fertile window, just before ovulation (2)

(1) Trussell J,and al. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception 1998; 57 : 363 – 69
(2) Wilcox AJ and al. On the frequency of intercourse around ovulation : evidence for bilological influences. Human Reprod 2004; 19 (7) : 1539 - 43
 Fertile window timelines

(1) Trussell J,and al. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception 1998; 57 : 363 – 69
(2) Wilcox AJ and al. On the frequency of intercourse around ovulation : evidence for bilological influences. Human Reprod 2004; 19 (7) : 1539 - 43
 Fertilization

Corona radiata cells

PHASE 1 Polar body PHASE 2

In division

Inner acrosomal
Membrane
Acrosome dissolves

Plasma
membrane Secondary oocyte
Sperm In 2nd meiotic division
nucleus

Fusion Oocyte and

Sperm cell
membranes PHASE 3

Main stages of fertilization

 From ovulation to implantation

Implantation of the fertilised

ovum Distance travelled in 3 to 5 days prior to Fertilisation
(7 days after fertilisation) implantation (up to 3-5 days after
unprotected
intercourse)

Ovulation

The oocyte is expulsed by the ovary, caught

The spermatozoa travel up the vagina by the ampulla and starts travelling up the
and uterus to reach the fallopian tube. fallopian tube towards the uterine cavity.
2. THE HISTORY OF EMERGENCY
CONTRACEPTION (EC)

21
 Contraceptive methods

Methods avoid pregnancy by blocking…

OVULATION FERTILIZATION IMPLANTATION

Hormonal methods: Barrier methods

pill, patch, ring, (condom, spermicidal, Intra-uterine devices
injection, implant diaphragm, …)

Traditional methods:
Emergency Fertility based methods,
Contraception temperature,
withdrawal

Sterilization

abortion is not a contraceptive method

 EC Definition

“…birth control that prevents pregnancy

after sex...”

23
 EC Definition

EC prevents pregnancy by inhibiting or delaying ovulation

There is no egg present to be fertilized by the sperm following sexual intercourse

EC should not be confused with abortion,

which acts after implantation
 When to use EC

EC may be required in a range of circumstances, where there is a

risk of pregnancy* :

1. Following sex where no contraception was used

2. Missed oral contraception pills
3. Condom failure (broken, dislodged or incorrectly used)
4. If a diaphragm or cap is incorrectly inserted, damaged,
dislodged or removed within 6 hours of sex
5. After use of the withdrawal method
6. Following rape or sexual assault

* Faculty of Family Planning and Reproductive health Care Clinical Effectiveness Unit. J Fam Plann Health care. 2006 Apr; 32 (2): 121 - 8; quiz 128.
25
 EC in the old times…

Abu Bakr Muhammad al-Razi (865 AD-925 AD)

• "First immediately after ejaculation let the two come apart and let the woman
arise roughly, squeeze and blow her nose seven times and call out in a loud voice.

• She should jump violently backwards seven to nine times."

26
 EC in the old times…

• Various methods have been tested for post coital contraception in the last decades
– High doses of vitamin C, aspirin or chloroquine
– Showers of coca cola, baking soda, urine

Family Planning Perspectives.1996;22:52-66 27

 Emergency contraception evolution

• 1920s: discovery that high-dose estrogens interfered with pregnancy in mammals

 Development of post-coital contraception began

• mid-1960s : high-dose estrogens were administered to a 13-year-old girl who had been raped
 First published study of this application in humans in the Netherlands

-Family Planning Perspectives.1996; 28 : 44 – 48

-Haspels AA, Andriesse R. High-dose estrogens 1973, Haspels AA. 1994
- Yuzpe AA, and al. Post coital – contraception. A pilot study; J Reprod Med 1974; 13(2) : 53 - 8. Yuzpe AA, Lancee WJ. 1977.
- Lippes . Postcoital IUD.1973

-Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral
contraceptives for emergency contraception. Lancet 1998; 352 : 428 – 33
- Van Look FA, von Hertzen H. 1993, levonorgestrel only.
- Guillebaud, J. 1998.
- Piaggio G et al. Lancet 1999; 353 (9154) : 721.
- Von Hertzen et al. 2002
 Yuzpe method

• Consists of :
- 200 µg of ethinyl estradiol and 1.0 mg of LNG (Europe & US)
- Half the dose is taken within 72 hours after unprotected intercourse
and the other half is taken 12 hours later

• Contraceptive efficacy :
reduction of pregnancy risk by 74 % (63-79) (1)

• Now proven to be significantly inferior to LNG in terms of :

efficacy, safety and simplicity of use (estrogen contraindications) (Cochrane ,2008)

• Yuzpe method products have already been withdrawn for several years (France, UK) or are
progressively being abandoned in favour of LNG products (Turkey, Spain)

(1) Trussell and al. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception 1998; 57 : 363 – 366
 Copper IUD (Intra Uterine Device)

• May be used for EC within 120 hours following unprotected intercourse

• Good efficacy and tolerability

– Pregnancy prevented in >96% of women
– Effective regular contraception

• Limitation:
– Since only specialists are trained to insert IUDs, difficult in an emergency
 Oral emergency pills
In more than 50
countries:
Europe (~ 20
countries)
Canada
Asia
Australia
Africa
United
States In ~ 40 countries:
Canada Europe
United States
Canada
In more than 20 Asia
countries: Australia
Europe New Zealand
US
Singapore Europe
Australia
New Zealand

31
 NorLevo® in 1999

• Administrated within 72 hrs of unprotected intercourse

– Two 0.75mg doses 12 hours apart or, as a single 1,5mg dose (1)

• More effective and better tolerated than the Yuzpe regimen

• No contraindications (2, 3)

• Limited efficacy
– Efficacy rate drops significantly with the time elapsed since unprotected intercourse,
especially after 48 hours (1, 3, 4)
– Oral hormonal EC is frequently administered more than 48 hours after unprotected
intercourse (20 to 25% of the time) (1, 2, 5)

1) Von Hertzen and al. A WHO multicentre randomised trial. Lancet 2002; 360 (9348): 1803 - 10.
2) Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral
contraceptives for emergency contraception. Lancet 1998; 352 : 428 - 33
3) Von Hertzen H et al. Lancet 1998; 352( 9144) : 1939
4) Piaggio G et al. Lancet 1999; 353 (9154) : 721
32
5) Gainer et al. Gynecol Obstet Fertil. 2005; 33 (6): 403 - 8
 ellaOne®
The new gold standard in emergency contraception

• EllaOne® is an oral emergency contraceptive

containing 30 mg of ulipristal acetate

• EllaOne is a SPRM = Selective Progesterone

Receptor Modulator

• First compound specifically developed for emergency

contraception

• More effective than NorLevo ®

• Indicated for use up to 120 hours after unprotected sex

or failure of a contraceptive method

• The European Commission granted a marketing authorization valid throughout the European
Union for ellaOne® to HRA Pharma on May 15, 2009

• FDA approval obtained on August 13, 2010 (unanimous votes at Advisory Committee)
• KLDA (South Korean agency) approval obtained on July 14, 2011
ellaOne®, the new gold standard

Ella has been launched in 33 countries

(Last updated, May 2012)
Countries where ellaOne® was launched
• Austria • Lithuania
• Belgium • Luxembourg
• Bosnia-Herzegovina • Netherlands
• Bulgaria • Norway
• Croatia • Poland
• Cyprus • Portugal
• Czech Republic • Republic of Korea
• Denmark • Romania
• Finland • Serbia
• France • Singapore
• Germany • Slovakia
• Greece • Slovenia
• Hungary • Spain
• Italy (April 2012) • Sweden
• Ireland • United Kingdom
• Israel • United States of America
• Latvia

(Last updated, May2012)

3. CONTRACEPTIVE ENVIRONMENT
ACROSS COUNTRIES

36
 Contraceptive Practices

Australia
USA
Canada Sterilisation

Switzerland
Netherlands
Germany
France LARC
Belgium Long Acting Reversible
Austria Contraception
Spain
Portugal Pill
Italy
Greece
United Kingdom
Sweden
Natural or barrier
Norway methods
Ireland
Denmark
0% 20% 40% 60% 80% 100%

Department of Economic and Social Affairs, Population Division (2009). Contraceptive prevalence among women in Union,
United Nations, World Contraceptive Use 2009 (POP/DB/CP/Rev2009)
37
 Unintended pregnancies

High rates of unintended pregnancies

Despite highly effective contraceptive methods available

 Unintended pregnancies
Intended and unintended Pregnancies by Region,2008

250
Pregnancy rate per 1000 women aged 15-44

Unintended
200 Intended
86

150

55 49
100
48
135 38
50
79 78
49 53

0
World Africa Asia* Europe North
America
* Except Japan

Singh S et al. Unintended Preganancy: Worlwide Levels, Trends, and Outcomes. Studies in Family Planning 2010; 41: 241-250.
 Unintended pregnancies
Unintended Pregnancies outcomes, 2008

Births
30% 28%
Abortions
Percentage pregnancy outcome

25%
Miscarriges
21%
(of all pregnancies)

20%
20% 18%

15% 13%

10%

5%

0%
World Africa Asia* Europe North America

* Except Japan

Singh S et al. Unintended Preganancy: Worlwide Levels, Trends, and Outcomes. Studies in Family Planning 2010; 41: 241-250.
 Unintended pregnancies occur under regular
contraception

Contraceptive use % Unintended pregnancies

100%

80%
65%
97 Contribute to 60%
France 40%
%
3% 20%
35%
0%

No contraception contraception
100%

80%

89% 48%
USA Contribute to 60%

40%

11% 20% 52%

0%

41
1) Bajos and al. Contraception: from accessibility to efficiency. Hum Reprod.2003; 18 (5): 994 – 9.
2) Wynn LL & Trussell J. Reducing unintended pregnancy in the United States. Contraception 2008; 77: 1-5
 Contraceptive failures

• 65% of unintended pregnancies are due to contraceptive failures

- 30% of which occurred with highly effective methods (Pill, IUD)

France: Population-based survey

23% 21%

12% 9%

Pill IUD Condom Other

Bajos et al. Contraception: from accessibility to efficiency. Hum Reprod., 2003; 18 (5) : 994 - 9
42
 EC is underused
Prospective cohort of French women (18 – 44 years old), Cocon Group

Study sample, n=2174

Inclusion/Exclusion Criteria:
• Sexually active women
• Not sterile, not pregnant, nor trying to get pregnant
during the entire year
• Not using an IUD during the entire year

Survey:
• Inconsistent use or failure using the contraceptive
method
• Period of sexual activity with no contraception

Women potentially at risk for

unintended pregnancy = 33%

Only 11% used EC

Goulard et al., Contraceptive failures and determinants of emergency contraception use. Contraception 2006; 74: 208-213
43
 Impact of EC on subsequent use of
regular contraception

Contraceptive use at the time of emergency contraception intake

Contraceptive use 6 months after emergency contraception intake

Highly effective 46%

methods 61%

Non-highly effective 39%

methods 28%

15%
No method
11%

0% 20% 40% 60% 80%

Highly effective methods: hormonal contraception: IUD, sterilization

Non-highly effective methods: condoms, spermicides, withdrawal or no method

C. Moreau et al.,The Effect of Access to Emergency Contraceptive Pills on Women's Use of Highly Effective Contraceptives:
Results From a French National Cohort Study.American Journal of Public Health (2008) Vol. 98, N°10
 Reasons women do not use EC (France)

Reasons for not using EC* %

Did not consider herself to be at risk of pregnancy 61.2
Did not think about EC 19.9
Thought it was too late to use EC 12.4
Did not know where to find EC 7.1
Did not know about EC 4.7
EC was too expensive 3.7
Thought EC would make her sick or was contraindicated 3.4
Was embarrassed to ask for EC 2.3
Thought EC was useless 2.2
Thought EC was an abortifacient 0.6

* Among 1,365 women undergoing induced abortions

* Moreau and al., Contraception 2005, France

45
 Reason for EC underuse

Unrecognised pregnancy risk

seems to be the most important barrier to the
use of EC

46
 Emergency Contraception
Lessons Learned

• Women experience difficulties with their regular contraceptives

– Women and providers should anticipate incorrect use and temporary
discontinuation
– EC provides a needed second chance to preventing pregnancy

• Misperception of pregnancy risk

– The need for EC presents a good opportunity to discuss
pregnancy risk

47
 4. HISTORY / CLINICAL DEVELOPMENT

17/04/2018
 ellaOne®
Ulipristal Acetate (UPA)

• UPA is a Selective Progesterone Receptor Modulator (SPRM) specifically

developed for EC

• UPA acts by binding with high affinity to the human progesterone

receptor

• UPA has an agonist and antagonist effects on the progesterone receptor

• Clinical development names:

– RTI 3021-012
(Research Triangle Institute)
– CDB-2914
– HRP-2000
– VA-2914
– UPA
 ellaOne®
Overall Clinical Development Program

PHASE I PHASE II PHASE III

Pharmacodynamic studies Pregnancy study

RCT UPA dose ranging RCT UPA 50 mg (nm) vs LNG
1, 10, 50, 100, 200 mg (nm) 0-72h
NIH-SPONSORED

At different times in cycle Creinin et al 2006

Stratton et al 2000
Pasarro et al 2003
Stratton et al 2009
Pregnancy study
RCT UPA 50 mg (nm) vs 10mg
0-72h
Unpublished study

Pharmacodynamic study Pregnancy study

HRA PHARMA-SPONSORED

RCT UPA 30mg vs PBO RCT UPA 30 mg vs LNG

At the time of LH peak 0-120h
Brache et al, 2010 Glasier et al, 2010

Pregnancy study
Open label UPA 30 mg
48-120h
Fine et al, 2010
 ellaOne®
Overall Clinical Development Program

Phase II (Creinin)
0-72h after UPI* (UPA / LNG)
Creinin et al. in Obstetrics & Gynecology 2006

Phase III (Fine)

48-120h after UPI (UPA)
Fine et al. in Obstetrics & Gynecology 2010

Phase III (Glasier)

0-120h after UPI (UPA/LNG)
Glasier et al. in Lancet 2010

* UPI : Unprotected Intercourse

 Phase II (Creinin)
Design

• 0-72h after unprotected intercourse

• Randomized & double blind comparative study

• Non-inferiority objective: “Is UPA as efficacious as LNG?”

• Multicenter based in US

• Number of women enrolled: 1672

Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 - 1097
 Phase II (Creinin)
Design

Enrolled (ITT*) 1549 women within

1672 72h intercourse

774 women 775 women

Primary Efficacy Population** followed up followed up
1549 after LNG after UPA
* Intention To Treat
** Excluding lost to follow-up, pre-treatment pregnancies & further EC intake

Levonorgestrel UPA 50 mg +
0.75mg x 2 placebo
Very few lost to follow-up = 6%
12 hours apart 12 hours later

Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 - 1097
 Phase II (Creinin)
Efficacy 0-72h

Pregnancy rates

1.7%
• Study success : UPA is at least as
efficacious as LNG when taken 0-72h
after unprotected intercourse
0.9%

• 7 pregnancies among UPA users 0.9%

[CI 0.2-1.6]

UPA LNG
(7/775) (13/774) • 13 pregnancies among LNG users 1.7%
[CI 0.8 -2.6]

Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 - 1097
 What is the expected pregnancy rate?
= Pregnancy rate that would have been observed without contraception
Conception No. of Patients Expected
Cycle day
Probability * with UPI ** Pregnancies
≤-6 0.00 240 0.0
-5 0.04 53 1.9
-4 0.14 56 7.6
-3 0.16 64 9.9
-2 0.28 65 18.0
-1 0.30 70 20.9
Ovulation 0.12 66 8.1
1 0.04 50 2.2
≥1 0.00 577 0.0
TOTAL 1.00 1241 68.6
% 5.5%

Conception Probabilities* Expected Pregnancies

0,4 According to Cycle Day for a given cycle day
=
0,2
Conception Probability
0
X
Day -5 Day -4 Day -3 Day -2 Day -1 Day 0 Day 1 Nb of Patients with UPI

* Pooled recognizable set provided by Trussell et al (1998) vol.57

* * Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase II (Creinin)
Efficacy 0-72h

UPA is at least as effective as LNG in preventing pregnancies

Pregnancy Prevention
85 % • Prevented fraction with UPA: 85%
[68%-93%]
69 % • Prevented fraction with LNG: 69%
[46%-82%]

Prevented fraction =

Expected PR – Observed PR

Expected PR
UPA LNG

Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 - 1097
 Phase II (Creinin)
Efficacy 48-72h

Signal of increased efficacy of UPA vs LNG for late intake

Pregnancy Prevention
93 %
• Prevented fraction with UPA: 93%
[52%-99%]
• Prevented fraction with LNG: 50%
50 % [0%-77%]

UPA LNG

Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 - 1097
 Phase II (Creinin)
Pregnancy outcome (ITT)

No sign of higher frequency of miscarriage

with UPA compared to LNG
26
PREGNANCIES

12 UPA 14 LNG

9 INDUCED ABORTIONS 8 INDUCED ABORTIONS

1 MISCARRIAGE 5 MISCARRIAGES
2 LOST TO FOLLOW-UP 1 LIVE BIRTH

Data on file, HRA Pharma, Clinical Study Report , Creinin 507

 ellaOne®
Overall Clinical Development Program

Phase II (Creinin)
0-72h after UPI* (UPA / LNG)
Creinin et al. in Obstetrics & Gynecology 2006

Phase III (Fine)
48-120h after UPI (UPA)
Fine et al. in Obstetrics & Gynecology 2010

Phase III (Glasier)

0-120h after UPI (UPA/LNG)
Glasier et al. in Lancet 2010

* UPI : Unprotected Intercourse

 Phase III (Fine)
Rationale

• No hormonal EC method currently available for a woman

presenting more than 72 hours after unprotected intercourse

• Efficacy of LNG decreases with time after unprotected intercourse

• Estimated lifespan of sperm in the genital tract is up to 5 days

• Sustained efficacy of UPA up to 3 days (seen in phase II trial, Creinin)

=> promising efficacy after 3 days

Decision to perform a late-intake study enrolling women

from 48 to 120h after unprotected intercourse

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Design

• 48-120h after unprotected intercourse

• Open label single arm Efficacité 1 étude de Phase III

• Single 30 mg dose of UPA

• Study objective: Is the pregnancy rate observed with UPA lower than:
o the estimated expected pregnancy rate* in the absence of contraception?
o the predefined clinical interest limit (4% = corresponding to half of the published
estimated expected pregnancy rate in the absence of contraception)?

• 45 sites based in US

• Number of women enrolled: 1533

*Trussell J and al. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception. 1998; 57(6): 363 – 369

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Design

Mean 24.4 years

Age
Range [18-50]
Enrolled
1533 Mean 25.3
B.M.I. (kg/m2)
Range [16.1 – 61.3]
White 61%
Primary Efficacy Population*
Black 21%
1241 Ethnic group
Asian 2.3%
•Excluding lost to follow-up, pregnancies not regarded as treatment Other 13.9%
failures, women aged > 35 and subsequent participation in the trial
History of
52%
pregnancy
Very few lost to follow-up = 6.7%
Previous EC use 52%

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Expected and Observed Pregnancy Rates

Study success: Statistical efficacy endpoints were met

Conception Number of Expected Observed
Cycle day Probability patients Pregnancies Pregnancies
≤-6 0.00 240 0.0 6
-5 0.04 53 1.9 0
-4 0.14 56 7.6 2
-3 0.16 64 9.9 1
-2 0.28 65 18.0 1
-1 0.30 70 20.9 2
Ovulation 0.12 66 8.1 2
1 0.04 50 2.2 4
≥1 0.00 577 0.0 8
TOTAL 1.00 1241 * 68.7 26

% 5.5% ** 2.1% ***

[1.4%, 3.1%]

- * Primary efficacy population ** Based on the conception probability cycle day (Trussell et al 1998) *** [95% CI]

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Efficacy Results by 24-hour Interval

Sustained efficacy of UPA up to 120h

after unprotected intercourse

Pregnancy rates
2.3%

2.1%

1.3%

48-72hrs 72-96hrs 96-120hrs

(16 / 693) (8 / 390) (2 / 158)

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Effect on Menstrual Cycle

Effect on cycle length

• UPA: increase by 2.8 days (mean) and 1 day (median);
4/5 women had menses +/- 1 week around expected date

Effect on menses
• No effect on menstrual volume
• No effect on duration of menses

Intermenstrual bleeding
• Observed rate 8.7%
• Of which 92% spotting

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Pregnancy Outcome

Frequency of miscarriage (20.7%) is not higher

than observed in general population

29
PREGNANCIES

16 INDUCED ABORTIONS
6 MISCARRIAGES

2 LIVE BIRTHS

5 LOST TO FOLLOW-UP

Data on file, HRA Pharma, Clinical Study Report, Fine study

 Phase III (Fine)
Most common related adverse events *

Headache 9.3%

Nausea 9.2%

Abdominal Pain 6.8%

Dysmenorrhoea 4.1%

Dizziness 3.5%

Fatigue 3.4%

*Adverse events that were assessed as certainly, probably or possibly treatment-related by the investigator
Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 Phase III (Fine)
Summary Results

Exposure
• 1533 women treated with UPA within 48 to 120h after UPSI

Efficacy
• Statistically significant reduction of the observed pregnancy rate with UPA
compared to the expected pregnancy rate in the absence of EC drug and also
compared to the clinical interest limit (4%)
• Sustained efficacy up to 5 days (120h)

Safety
• Delay in next menses (2-3 days on average) / No other effect on cycle
• Majority of AEs were mild or moderate

Fine P and al. Ulipristal acetate taken 48 – 120 hours after intercourse for emergency contraception. Obstetrics & Gynecology 2010; 115 : 257 - 263
 ellaOne®
Overall Clinical Development Program

Phase II (Creinin)
0-72h after UPI* (UPA / LNG)
Creinin et al. in Obstetrics & Gynecology 2006

Phase III (Fine)
48-120h after UPI (UPA)
Fine et al. in Obstetrics & Gynecology 2010


Phase III (Glasier)

0-120h after UPI (UPA/LNG)
Glasier et al. in Lancet 2010

* UPI : Unprotected Intercourse

 Phase III (Glasier)
Design

• Within 120h after unprotected intercourse

• UPA vs LNG

• Randomised single blind comparative trial

• Non-inferiority study

• 35 Family Planning clinics in UK, Ireland & USA

• Number of women enrolled: 2221

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 - 562
 Phase III (Glasier)
Design - Study Flow Chart

2221 Enrolled

1104 UPA exposed 1117 LNG exposed

941 958
Primary Efficacy* Primary Efficacy*
Population Population

•Excluding lost to follow-up, pre-treatment pregnancies, women aged > 35 and

subsequent participations in the trial

Very few lost to follow-up women (4%)

- Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562
- Data on file, HRA Pharma, Clinical Study Report, Study 513,
 Phase III (Glasier)
Profile of Exposed Women

UPA LNG
Treatments
(n=1104) (n=1117)

Mean 24.5 years Mean 24.9 years

AGE
Range [16-52] Range [16-55]

Mean 25.3 Mean 25.2

B.M.I. (kg/m2)
Range [15.8 – 70] Range [14.9 – 53.7]

White 72.8% White 72.4%

Black 19% Black 18.5%
ETHNICITY
Asian 1.2% Asian 1.9%
Other 7% Other 7.2%

HISTORY OF PREGNANCY 47.3% 47.8%

PREVIOUS EC USE 54.9% 55.7%

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375
: 555 – 562
 Phase III (Glasier)
Efficacy Results 0-72h

UPA is at least as efficacious as LNG < 72h

UPA LNG
Treatments

Number of Subjects (Primary 844 852

Efficacy population)
Number of Observed 22
15
Pregnancies
Expected Pregnancy Rate
(in the absence of 5.5% 5.4%
contraception)
Overall Observed Pregnancy
1.8% 2.6%
Rate
[1.0%, 3.0%] [1.7%, 3.9%]
[95%CI]

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375
: 555 – 562
 Phase III (Glasier)
Efficacy Results 0-120h

UPA is at least as efficacious as LNG < 120h

Treatments UPA LNG

Number of Subjects (Primary

941 958
Efficacy population)

Number of Observed Pregnancies 15 25

Expected Pregnancy Rate

5.7% 5.5%
(in the absence of contraception)

Overall Observed Pregnancy Rate

1.6% 2.6%
*

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375
: 555 – 562
*CI is not available
 Phase III (Glasier)
Efficacy by 24h interval

UPA is at least as efficacious as LNG

Pregnancy Rate

3.0% 3.0%
2.7%
2.6%
2.1% 2.2%
1.6% 1.5% UPA

LNG
0.0% 0.0%

0-24h 25-48h 49-72h 73-96h 97-120h

(n=649) (n=648) (n=399) (n=136) (n=67)

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375
: 555 – 562
 Phase III (Glasier)
Prevention Rate

Compared to the expected pregnancy rate,

significantly more pregnancies were prevented with UPA than with LNG

Time Window Prevention Rate Prevention Rate Difference p value

(Randomization
UPA LNG one sided test)

0 to 120 h 4.2% 2.9% 1.3% p = 0.043

Prevention Rate = Expected PR – Observed PR

Exposed

Data on file, HRA Pharma, Clinical Study Report, Study 513

 Phase III (Glasier)
Pregnancy Outcome

No sign of higher frequency of miscarriage

with UPA compared to LNG
Data on file, HRA Clinical Study Report
50
PREGNANCIES

20 UPA 30 LNG

14 INDUCED ABORTIONS 21 INDUCED ABORTIONS

5 MISCARRIAGES 5 MISCARRIAGES

1 LOST TO FOLLOW-UP 3 LIVE BIRTHS

1 LOST TO FOLLOW-UP

Data on file, HRA Pharma, Clinical Study Report, Study 513. NB : updated information compared to Glasier and al. in Lancet 2010
 Phase III (Glasier)
Effect on Menstrual Cycle

• Increase of the cycle length with UPA

• No impact observed on other cycle parameters

UPA LNG
Treatment Change from Treatment Change from
Cycle Screening Cycle Screening
Number of patients 1104 1011 1117 1031
Mean (sd) 30.8 + 2.1* 27.5 -1.2*
Cycle length
(days)
Median 30 +1 28 -1

*Comparison UPA vs LNG, p< 0.05

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562
 Phase III (Glasier)
Most frequent adverse events

• Similar Adverse Events profile between UPA & LNG

 Phase III (Glasier)
Conclusions

Efficacy results
• More pregnancies prevented with UPA than LNG
• UPA is efficacious up to 5 days (120h) after unprotected intercourse

Safety results
• UPA well tolerated in over 1000 women treated
• Similar adverse event profile as LNG
• Mean increase in cycle length of 2.1 days with UPA

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562
 Meta-analysis
Combined Data from the 2 Comparative Trials

Phase II (Creinin)
0-72h after UPI* (UPA / LNG)
Creinin et al. in Obstetrics & Gynecology 2006

Meta-analysis
(Creinin & Glasier)
Glasier et al. in Lancet 2010

Phase III (Glasier)

0-120h after UPI (UPA/LNG)
Glasier et al. in Lancet 2010

* UPI : Unprotected Intercourse

 Meta-analysis (Creinin & Glasier)

ellaOne® is more effective than levonorgestrel

1

Creinin Trial (1)

0.18 0.50 1.24 (0-72hrs)
n = 1 546

0.29 0.57 1.09 Glasier Trial (2)

(0-120hrs)
n = 1 899

0.32 0.55 0.93 Meta analysis (2)

(0-120hrs)
n = 3 445

Efficacy in individual trials and for meta-analysis

Odds ratio* (UPA / LNG) and 95% CI

(1) Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 – 1097
(2) Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010;
375 : 555 – 562
 Meta-analysis (Creinin & Glasier)

• EllaOne® is nearly 3 times more effective than LNG when taken

within 24hrs after UPSI
• EllaOne® is almost twice more effective than LNG when taken
within 72 hours after UPSI
1

Meta analysis
0.32 0.55 0.93 (0-120hrs)
n = 3 445

Meta analysis
0.33 0.58 0.99 (0-72hrs)
n = 3 228

0.11 0.35 0.93 Meta analysis

(0-24hrs)
n = 1 180

Odds ratio (UPA / LNG) and 95% CI

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562
 Conclusion
ellaOne® Overall Clinical Development

• ellaOne® provides women and health care providers with a more effective
alternative for emergency contraception that can be prescribed up to 5 days
after UPI

• ellaOne® is more effective than levonorgestrel from 0-72 hours

 From 0-24 hours, the difference is greater still

• Compared to levonorgestrel, ellaOne® reduces pregnancy risk by almost:

 2/3 for intake within 24 hours following UPI
 1/2 for intake within 72 hours following UPI

• ellaOne® has a similar tolerability profile as levonorgestrel

5. EFFICACY AND SAFETY IN SUMMARY
 The risk of an unplanned pregnancy almost halves
with ellaOne vs. levenorgestrel within 72hrs of UPI

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562
 The risk of an unplanned pregnancy drops by almost two-thirds
with ellaOne vs. levenorgestrel within 24 hrs of UPI

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562
 ellaOne’s safety profile is comparable to levenorgestrel

Glasier A and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 – 562

88
6. MECHANISM OF ACTION
 First Representative of a New Therapeutic Class
(SPRM)*, developed for EC

ellaOne® acts via selective binding to human progesterone receptor **

•Reduced affinity for other nuclear receptors

• Antagonism of endogenous progesterone in animal models
• Various degrees of progesterone agonist activity in in vitro cellular models
• Agonist-like effect on pituitary LH, mixt agonist-antagonist effects on
endometrium in vivo

* Selective Progesterone Receptor Modulator

** European Summary of Product Characteristics
 ellaOne® mechanism of action

Ulipristal acetate, a selective progesterone receptor

modulator, given in the mid-follicular phase ( dominant
follicle size 14-16 mm)

 causes a dose dependent delay in follicular rupture

Stratton and al. A single mid-follicular dose of CDB - 2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling
women.
Human Reproduction 2000; 15 (5):1092 - 99
 ellaOne® mechanism of action

Ulipristal acetate, 30 mg, given in the late follicular phase

(dominant follicle size 18 mm)

 still causes a delay in follicular rupture in a large

proportion of women

Brache and al. Immediate preovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Human Reproduction 2010; 25 (9): 2256 - 2263
 ellaOne®, significantly delays ovulation,
even when LH surge has started1

... a time when LNG appears to be no longer effective 2

1. Brache et al., Immediate preovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Human Reproduction 2010; 25 (9): 2256 –
2263
2. Croxatto HB and al. Pituitary ovarian function following the standard levonogestrel emergency contraceptive dose or a single 0.75 mg dose given on the days
preceding ovulation. Contraception. 2004; (70) : 442 - 450
ellaOne® postponed follicular rupture

Late
Mid

ellaOne®

Ovulation delayed
 ellaOne® mechanism of action
Conclusions

• ellaOne®, administered in the advanced follicular phase, inhibits or delays

follicular rupture

• This effect seems to be mediated by LH surge inhibition or delay

• ellaOne® could prevent pregnancy when administered very late in the

follicular phase, even if the LH levels have already begun to rise, a time
when LNG appears to be no longer effective in preventing follicular
rupture

• In practice, due to the high variability and unpredictability of the fertile

window, it’s recommended to prescribe ellaOne® regardless of cycle day
of UPI
7. POST MARKETING STUDIES
 Outline

• Pregnancy registry
• Pregnancy study (Ellipse)
• Pediatric study (STEella)
• Lactation study
• Off-label ellaOne® survey
 Pregnancy Registry

 To assess clinical follow-up and outcome of pregnancies resulting from

ellaOne failure or pregnancies inadvertently exposed to ellaOne ®.

• Web based registry for prescribers: http://www.hra-pregnancy-registry.com/en/

• Available in all European countries where ellaOne® is marketed
• Prescribers informed through mailing of educational material (DDL) at time of
launch, local, national and international scientific meetings/conferences

• Reporting on a voluntary basis

 Pregnancy Study (ellipse)
Objectives

 To evaluate pregnancy outcome and follow – up on pregnancies

exposed to ellaOne® / ella® or resulting from ellaOne® / ella® failure:

• To estimate the rates of outcomes of pregnancies exposed to ellaOne® /ella®

(whether due to failure of the emergency contraception or inadvertent
exposure during pregnancy)

• To collect data on birth complications in case of pregnancies exposed to

ellaOne® /ella®

• To assess the nature and incidence of complications of pregnancy loss in

pregnancies exposed to ellaOne® /ella®

• To assess adverse events during the course of pregnancies exposed to

ellaOne® /ella®
 Pregnancy Study (ellipse)
Design & Timelines

• Observational
• Multicenter
• Europe (Germany, France, UK and Spain) and US
• 1000 investigators
• Recruitment objective: 500 women in 2 years maximum
(NB: sample size objective to be revised if not achieved
after 2 years)

Milestones Timelines
Dec 2009 (EMEA)
Protocol approval
Q1 2011 (FDA)
First site initiated Q2 2011
End of recruitment Q4 2013
Final Clinical Study Report Q1 2015
 Pediatric Study (STEella)

Primary objective

To assess the safety and tolerability of ellaOne® /ella® in routine

conditions of use for emergency contraception, in post-menarchal adolescents
and adult women, in particular menorraghia, metrorrhagia, dysmenorrhea and
effect on menstrual cycles

Secondary objective

To assess the pregnancy rate observed after taking ellaOne®/ella® for
emergency contraception in routine conditions, in post-menarcheal
adolescents and adult women

To follow-up pregnant women throughout the pregnancy (check of

potential complications) including fetal and neonatal follow-up
 Pediatric Study (STEella)
Design & Timelines

• Observational study
• Multicenter
• Europe (Sweden, UK, France) and US
• 500 women to be recruited
• 350 women to complete the study (half in each population)

Milestones Timelines
First site initiated May 2010
Final Clinical Study Report December 2012
 Lactation Study
Objectives, Design & Timelines

 To determine the distribution of ulipristal acetate into breast milk and

evaluate the potential exposure on the suckling infant following a
single dose of 30 mg of ulipristal acetate in order to formulate clinical
recommendations for breastfeeding following ulipristal acetate intake

• Prospective, single-arm, open-label

• Sampling period during the 120 hours following administration of
a single dose of UPA 30mg
• 10 healthy women
• Chile

Milestones Timelines
Site Initiated Q2 2011
Clinical Study Report Q2 2012
 Off-label ellaOne® Survey
Objectives, Design & Timelines

 To assess the potential off-label use of ellaOne® among prescribers in Europe

 To evaluate the use and experience of ellaOne® more than two years after
launch among prescribers in Europe

• Survey among physicians/HCPs

• Europe: France, Germany, UK, Sweden, Portugal, Poland
• Qualitative phase: 90 physicians/HCPs interviewed face to face or by phone
• Quantitative phase: 300 physicians/HCPs interviewed through internet
questionnaire

Milestones Timelines
Qualitative phase report Q2 2011
Quantitative phase report Q2 2012
8. ELLAONE® IN PRACTICE /
RECOMMENDATIONS
 ellaOne®
From Clinical Studies to Clinical Practice

• A pooled data of two randomized controlled trials (Creinin(1) and Glasier(2) ) have
showed a statistical significant higher efficacy for ellaOne® vs. LNG

• ellaOne® significantly delays follicular rupture, even when administered at the time
of the LH peak onset, a time when both conception probability and intercourse
frequency are the highest

How to transpose this data into “real clinical practice”?

(1) Creinin MD and al. Progesterone receptor modulator for emergency contraception. Obstetrics and Gynecology 2006; 108 : 1089 - 1097

(2) Glasier F and al. Ulipristal acetate versus levonorgestrel for emergency contraception : a randomized non - inferiority trial and meta – analysis. Lancet 2010; 375 :
555 - 562
 ellaOne® in practice
How to use?

• The treatment consists of one tablet to be taken orally as soon as possible after
unprotected sexual intercourse, and at the latest within 120hrs (5 days)

• ellaOne® can be taken at any point during the menstrual cycle

• The tablet can be taken with or without food

• If vomiting occurs within 3 hours of ellaOne® intake, another tablet should be

taken

• Pregnancy should be excluded before ellaOne® is administered

SPC , Nov 2011.Europe

 ellaOne® in practice
Pharmacokinetics & Metabolism

 Rapidly absorbed :
• Peak plasma concentration 0.5 - 3 hours after ingestion

UPA

profiles of UPA and its metabolite 3877A

following a single 30 mg dose

3877A

• pH-dependent absorption
• High binding (>98%) to plasma proteins
• Metabolism: liver (CYP3A4)
• Terminal half-life in plasma: 32.4 ± 6.3 hours
 Rapidly eliminated

SPC , June 2009 in Europe

 ellaOne® in practice
Effects on period

• The majority of women (80.8%) had their menstrual period at the

expected time or within +/- 7 days

• Treatment cycle length was 2 to 3 days longer on average

• Menstrual periods are of normal duration and volume

• Intermenstrual bleedings
• Observed in only a minority (8.7%) of women
• Reported as spotting in the majority of cases (91.8%)
• Heavy intermenstrual bleeding reported in only 5 women (0.3%)

SPC , Nov 2011.Europe

 ellaOne® in practice
Drug Interaction (1)

Can a regular method of hormonal contraception be continued at

the same time as giving ellaOne ® ?

• UPA binds the progesterone receptor with high affinity, so it may interfere with
the action of progestogen-containing medicinal products

• It’s recommended that after using ellaOne®, a reliable barrier method is used
until the next period

• Concomitant use of emergency contraception containing LNG is not

recommended

SPC , June 2009 in Europe

 ellaOne® in practice
Drug Interaction (2) & Contraindications

Which medicinal products interfere with ellaOne® ?

– CYP3A4 inducers (e.g rifampicin, phenytoin, phenobarbital, carbamazepine,
St John’s wort) may reduce plasma concentrations of ellaOne® and
decrease efficacy
– Products that increase gastric pH (e.g proton pump inhibitors, antiacids, H2-
receptors agonists) : reduce absorption and may affect efficacy
– Potent CYP3A4 inhibitors (e.g ketoconazole, itraconazole, telithromycine,
ritonavir, clarithromycin, nefazodone) may increase exposure to ellaOne®.
The clinical relevance is unknown

Are there contraindications to taking ellaOne®?

– Pregnancy
– Hypersensitivity to the active substance or any of the excipients

SPC , June 2009 in Europe

 ellaOne® in practice
Pregnancy & Lactation

What are the effects of ellaOne® on the foetus following inadvertent intake ?

In clinical trials, no teratogenic effects were observed. Nevertheless, as for many new
molecular entity, extremely limited data are available on the health of the foetus / new–born
in case of exposure to ellaOne® during pregnancy.

Note: As of Nov 2011, 39 pregnancies with known outcome: 30 termination,

5 miscarriage & 4 healthy babies

What are the effects of ellaOne® on Breastfeeding ?

Lipophilic compound, potential excretion in milk but no specific data.
Not recommended for at least 36 hours after ellaOne® intake (pending results of lactation study).
 ellaOne® in practice
Conclusions

• ellaOne® should be offered at any point during the menstrual cycle

• ellaOne® should be prescribed as soon as possible after unprotected

intercourse and up to 120h

• No contraindications with hormonal contraceptive pills

• Regular oral contraceptives can be started immediately after ellaOne®

intake, but use of a barrier method until the next menses is recommended

• Contraindications : on-going pregnancy and hypersensitivity to the active

substance or any of the excipients

• Lactating women may choose LNG or should avoid breastfeeding

for 36h after ellaOne® intake
 ellaOne® conclusions

• ellaOne® is the new gold standard in EC

• ellaOne® is more effective than levonorgestrel

• ellaOne® is effective right up to the point of ovulation

• ellaOne® has a safety profile comparable to levonorgestrel