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ProPharma Partners International, Inc.
Cyclic Mastalgia: A Large, Misunderstood
Medical Condition
Analysis completed by Paulo Rangel
June 2011
Contacts: James Chubb, Ph.D.
Founding Partner
[email protected]
Paulo Rangel
Partner
[email protected]
www.propharmap.com
Cyclic Mastalgia: A Misunderstood and
Generally Undertreated Medical Condition
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Over 10 MM women in the USA suffer from moderate to severe
cyclic mastalgia
…their sleep, work, physical and sexual activity are all
affected
Many providers and pharmaceutical companies view CM as a
“lifestyle” condition and fail to place sufficient importance on
the condition…
…women who suffer from CM are of a different opinion
First line therapy is NSAIDs, hot compresses and comfortable
clothing, which are all marginally effective
The successful drug may achieve $500 MM in USA revenue…
…Women with CM need a better treatment
The Analysis
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The objective of this analysis is to convey the potential for
the cyclic mastalgia market
The condition, current treatments and the unmet need are
described
Further analysis has been completed for a specific drug
candidate (not included here)
Table of Contents
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The Cyclic Mastalgia Opportunity
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Cyclic Mastalgia Market Size
Cyclic Mastalgia
The Opportunity
What is Cyclic Mastalgia?
• Breast pain can be classified as cyclic mastalgia, noncyclic
mastalgia and extramammary pain (non-breast) (1)
• Cyclic mastalgia is the most common form of breast pain and has a
clear association with the menstrual cycle. It most commonly
affects premenopausal women between the ages of 20 and 45. (2)
• Cyclic mastalgia description (2)
• Most often bilateral and diffuse pain
• Caused by normal hormonal changes associated with ovulation that
stimulate the proliferation of normal glandular breast tissue and results
in pain
• Usually presents a week prior to the onset of menses and dissipates
with menses
• Becomes more severe over time
(1) Smith et al. "Evaluation and Management of Breast Pain." Mayo Cin. Proc. 2004;79:353-372
(2) "Breast Pain." Up-to-date
What is the prevalence (USA)?
Women 20-45 yrs of age (USA)

51,347,252 (1)
Women with cyclic mastalgia
Severity: 4+; Duration: 5-6 days
4.62 MM (9%) (2)
Women with cyclic mastalgia
Severity: 4+; Duration: 7+ days
5.65 MM (11%) (2)
Women with moderate to
severe cyclic mastalgia
10.27 MM (20%)
(1) USA Census
(2) Ader et al. “Prevalence and impact of cyclic mastalgia in the United States clinic-based
sample.” Am J Obstet Gynecol. Volume 177, Number 1
Over 10 million women
in the USA have
moderate to severe
cyclic mastalgia!
How serious is cyclic mastalgia?
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Consequences of cyclic mastalgia are not trivial (1)
•
•
•
•
10% affected sleep
6-13% affected work, school and social functioning
36% affected physical activity
48% affected sexual activity
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Women also experience increased anxiety and depression (1)
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Women interviewed reported (2)
• An average pain score of 5.3 (scale of 1-10)
• Median time with cyclic mastalgia of 13.5 years
• On a monthly basis
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33% have pain for 7+ days
93% have pain for 3+ days
(1) Smith et al. "Evaluation and Management of Breast Pain." Mayo Can. Proc. 2004;79:353-372
(2) Primary Research
Current Treatment
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Physician recommended treatment
• First line: NSAIDs, application of heat, dietary changes
• Second line: Tamoxifen (10 mg daily)
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Tamoxifen is the most effective treatment for cyclic mastalgia
Use of Tamoxifen is limited because of significant side effects
• Third line: Danazol (200 mg daily); limited to 6 months
• Fourth line: Goserelin depot injection (3.6 mg/month)
• Other options
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Oral contraceptives
Bromocriptine
Physicians want a patient to try a treatment for 2-4 months to evaluate
its effectiveness
Danazol, bromocriptine, goserelin and tamoxifen are rarely used in
practice because they are poorly tolerated
Goyal, Amit and Mansel, Robert, "Mastalgia." Management of Breast Diseases, Chapter 4
How is Cyclic Mastalgia Treated?
Workup of any mass/cyst
Patient with Mastalgia
Patient requesting treatment
Reassurance/Lifestyle advice
Cardiff’s Algorithm for the
Management of Mastalgia
Breast Pain
NSAID
Oral or Topical
x3 months
Musculoskeletal pain
Good
response
Oral or Topical NSAID
Discharge
Injections of steroid or local anesthetic
into tender site
Poor response
Tamoxifen
10mg/d x3 months
Good
response
Persistent pain
Tamoxifen
10mg/d x3 mo
Poor response
Danazol
200mg/d x3 months
Good
response
Danazol
100mg/d x3 mo
Poor response
Goserelin
3.6mg/month x6 mos.
Source: Goyal, Amit and Mansel, Robert, "Mastalgia." Management of Breast Diseases, Chapter 4
What is the Unmet Need?
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Cyclic mastalgia affects a large number of women, alters their daily
activity and can result in increased anxiety and depression
Current therapies have minimal efficacy or are limited by significant
side effects
• First line therapy (NSAIDs, hot compresses, comfortable clothing,
evening primrose, etc.) is minimally effective
• Stronger therapies such as Danocrine, bromocriptine and tamoxifen are
rarely used because of side effects
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There are very few therapies currently in development for cyclic
mastalgia
Women need an alternative to existing therapies
Comments from a Key Opinion Leader
Robert Mansel, M.D.
Click on box to play video
Cyclic Mastalgia is a Compelling Target Market
Available therapies are marginally effective and/or
associated with adverse events
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Cyclic mastalgia is poorly understood and often minimized by health care
providers
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It is the most common form of breast pain and represents a clear, unmet need
•
•
•
•
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More than 10 MM women have moderate to severe cyclic mastalgia
CM affects sleep, physical and sexual activity and often leads to anxiety and
depression
Women indicated in primary research that they have had cyclic mastalgia for a
median of 13.5 years; it is persistent and long-lived
Current therapeutics are marginally effective or have significant side effects that
limit their use
An effective and well tolerated therapy could achieve sales of $250-500 MM in
the United States alone [based on a broader analysis]
Cyclic Mastalgia Market Size
Use of the patient flow chart
Patient Flow Model
To estimate the revenue potential of a product in cyclic mastalgia, a patient
flow model is utilized. For a particular drug candidate, boxes 4-8 need to be
determined based on primary and/or secondary market research
1
Total Prevalent Patients
2
Patients Seeking Treatment
3
Diagnosis Rate
4
Treatment Rate
5
Market Penetration
6
Doses/Per Patient/Per Year
7
Price
8
Gross Revenue
 The patient flow is used to estimate the revenue potential for
a product
 Each box should be supported by primary and/or secondary
market research
 In some cases, no data sources may not be available. In
such instances, team estimates are relied upon.
 Due to these limitations, quantitative outputs should be
considered directional only.
Cyclic Mastalgia Patient Flow (USA)
Prevalence (USA)
(women 20-45 yrs)
51,347,252
Total Population
Severity 4+ &
Duration 5-6 days
4.62 MM (9%)
Diagnosis Rate
Patients Seeking
Treatment 6.0 MM
(58%)
Severity 4+ &
Duration 7+ days
5.65 MM (11%)
Diagnosis Rate
4.17 MM (70%)
> 10 MM target
patients in the USA
1
Total Prevalent Patients
Cyclic Mastalgia: Prevalence
• In a study that included 632 premenstrual women attending an
Ob/Gyn clinic in the USA, 67% experienced premenstrual
discomfort in the past 6 months (1)
•
11% of premenopausal women have “clinical mastalgia” as defined by…
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•
An additional 9% of premenopausal women have
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VAS of 4 cm or more (scale of 1-10)
Pain duration of 7 or more days per month
VAS of 4 cm or more (scale of 1-10)
Pain duration of 5-6 days per month
20% of premenopausal women with cyclic mastalgia experience
moderate to severe pain symptoms (1)
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In a survey of working women in South Wales…(2)
•
•
45% described mild breast pain
21% described severe breast pain
(1) Ader et al. “Prevalence and impact of cyclic mastalgia in the United States clinic-based
sample.” Am J Obstet Gynecol. Volume 177, Number 1
(2) Smith et al. "Evaluation and Management of Breast Pain." Mayo Clin. Proc. 2004;79:353-372
2
Patients Seeking Treatment
Cyclic Mastalgia: Patients Seeking Treatment
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Minor breast discomfort and swelling within a few days of the onset
of menses is normal (1)
Women will usually start by treating themselves (2)
•
•
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Reasons for seeking treatment (2)
•
•
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Most often, women start with over-the-counter analgesics
OTC analgesics demonstrate only minimal benefit
Concerns about cancer may prompt a woman to seek treatment
Women may mention their breast pain during a scheduled visit, but 1-2 years
may pass before she mentions the pain to her doctor
Primary research indicated that 58% of women with moderate
to severe cyclic mastalgia had discussed their pain with a
professional (2)
(1) Smith et al. "Evaluation and Management of Breast Pain." Mayo Clin. Proc. 2004;79:353-372
(2) Primary Research
2
Patients Seeking Treatment
Cyclic Mastalgia: Patients Seeking Treatment (2)
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58% of women had discussed their pain with a professional
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Type of health care professional (numbers indicate that some
women spoke with more than one type of health care professional)
•
•
•
•
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86% - Ob/Gyn
44% - General Practitioner
25% - Nurse practitioner
20% - Professional at women's health or breast care center
Ob/Gyn providers are the key target to drive sales in this market
(1) Primary Research
3
Diagnosis Rate
Cyclic Mastalgia: Diagnosis Rate
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Diagnosis approach (1)
• History. Identify and characterize breast-related symptoms
• Physical examination. Determine area of pain; physical
abnormalities (mass, nipple discharge, etc.) have precedence
• Mammogram. Rule out any underlying problem (e.g., breast
cancer) – it is rare that pain alone is an indication of breast cancer
• Prospective assessment with a daily breast pain diary to
document the occurrence and severity of pain
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Diagnosis based on recall of symptoms is 65% sensitive
Diagnosis based on a prospective breast pain diary is 69% specific
Based on the literature, the diagnosis rate is 70%
(1) Smith et al. "Evaluation and Management of Breast Pain." Mayo Clin. Proc. 2004;79:353-372
Patient Flow Diagram for a Particular Product Opportunity
Various drivers of gross revenue are determined on a product-by-product basis
Prevalence (USA)
(women 20-45 yrs)
51,347,252
Total Population
Severity 4+ &
Duration 5-6 days
4.62 MM (9%)
Treatment Rate
Patients Seeking
Treatment 6.0 MM
(58%)
Severity 4+ &
Duration 7+ days
5.65 MM (11%)
Diagnosis Rate
4.17 MM (70%)
Market
Penetration
Penetration Rate
Doses/Per
Patient/Year
Annual Doses per
Patient
Price
Price
Gross Revenue
Gross Revenue
Treatment Rate
Expanded Summary of CM Treatment Options
Product
Comments
Conservative (1)
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Support garments (well-fitting brassiere); warm compresses or ice packs
Evening primrose (2)
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Data is conflicting; efficacy is not clear. Prescription license revoked in the UK in 2002.
Acetaminophen; NSAIDs (1)
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Acetaminophen, NSAIDs or both may be tried early (usually first line therapy)
Pain may be dulled but not eliminated (from primary research)
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Not in widespread use for cyclic mastalgia
Uncontrolled, non-blinded study at one center in Turkey measured VAS scores at the start and at 6
months; demonstrated a statistically significant drop in pain in the treatment group vs the placebo
group
Topical treatment was applied 3 times per day (every 8 hours) for 6 months
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Success rate is 71-96%, but there are significant side effects which limit its use
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Topical NSAIDs (3)
Tamoxifen (3)
Danazol
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A synthetic testosterone that binds to progesterone and androgen receptors, exhibits a wide
spectrum of systemic adverse effects including the potential of teratogenicity
Severe side effects in 30% of cases (5)
Indicated for the short-term treatment (up to 6 months) of severe benign (fibrocystic) breast disease
or mastalgia associated with severe symptomatic benign breast disease, in patients refractory to
other treatments (4)
Gonadotropin releasing
hormone agonists (2)
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Demonstrated efficacy in an uncontrolled study with 21 women
Adverse events significant – hot flashes, headache, fatigue, nausea, depression
Used only of all other pharmacologic treatments do not work
Bromocriptine
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Dopamine agonist. Has demonstrated efficacy, but very significant side effects.
Severe side effects in 35% of cases (5)
(1)
(2)
(3)
(4)
(5)
"Breast Pain." Up-to-date
Smith et al. "Evaluation and Management of Breast Pain." Mayo Clin. Proc. 2004;79:353-372
Colak et al. "Efficacy of Topical Nonsteroidal Anti-inflammatory Drugs in Mastalgia Treatment." J. Am Coll Surg; Vol. 196, No. 4, April
2003
Danocrin Prescribing Information
Gateley et al. “Drug treatments for mastalgia.” J of the Royal Society of Medicine. Vol. 85 January 1992
ProPharma Partners
International, Inc.
Contacts:
James Chubb, Ph.D.
Founding Partner
[email protected]
Paulo Rangel
Partner
[email protected]
www.propharmap.com