Cysteamine Intro PDF

I n t e n s i v e Pig m e n t C o r r e c t o r
Cysteamine Made in Switzerland
Cysteamine
The Novel Treatment for Melasma
and other Hyperpigmentation Disorders
Behrooz Kasraee, MD
Scientis Pharma SA,
Geneva, Switzerland
© Scientis Pharma 2018 1
Current status of skin depimenting agents
• Hydroquinone has been used for

decades in the treatment of
hyperpigmentary disorders.
• Although still very controversial,

hydroquinone has got a bad reputation
as a mutagenic compound
• Non-hydroquinone compounds such

as kojic acid, arbutin, azelaic acid,
retinoids, hydroxy acids etc. have a
lower efficacy

An effective and safe skin depigmenting agent
is intensely sought after by the healthcare community
to replace hydroquinone

What is cysteamine?
Cysteamine is the simplest aminothiol physiologically produced

in human cells from the essential amino-acid cysteine

Cysteamine biosynthesis pathway in human cells

Estimated values of cysteamine concentration in nutrients

Courtesy of Dr. Larry Wu (Singapore) © Scientis Pharma 2018 7

In the 60s, Cysteamine was shown to be a depigmenting

agent significantly stronger than hydroquinone in vivo
In 1966, Chavin injected Cysteamine

into black goldfish skin and observed
significant skin depigmentation
In 1968, studies by Frenk,

Pathak and Bleehen showed
that Cysteamine is
significantly stronger than
hydroquinone in vivo
but its odor prohibited its use

in topical products
Chavin W. et al, 1966, Die Naturwissenschaften 53(16):413-414

E Frenk et al. Arch Dermatol 97 (4), 465-477. 4 1968
SS Bleehen et al. J Invest Dermatol 50 (2), 103-117. 2 1968
80% reduction of melanin synthesis in B16 melanocytes

in In vitro study on the depigmenting effect of Cysteamine
80% melanin
synthesis
reduction
Control Cysteamine
Qui L. et al, J. Invest Dermatol. 2000 Jan;114(1):21-7

In 2010-12
Scientis Pharma developed a new technology
that significantly increases cysteamine stability
and reduces its odor
Usable Topically = Significantly reduced odor

A first case series gave clues about

the significant efficacy in melasma patients
by Hsu et al, 2013

© Scientis Pharma 2018 I confidential

A double-blind, randomized, vehicle-controlled

clinical study in 2015
by Mansouri et al, 2015

Heinz Maurer Award 2017 for Skin Surface Research in Ethnic Population

Other clinical trials have confirmed the results
"Significant efficacy in decreasing melanin content of

melasma lesions”, by Farshi et al, 2018

77% melanin index reduction in melasma lesions

by cysteamine (vs. control, measured by Mexameter, BJD 2015)
65.2 63.7 63.8 63.6

70
77% melanin
29.9 index reduction
14.2
0 P = 0.79 P = 0.001 P = 0.0001
Week 0 Week 8 Week 16
Mansouri et al, 2015, BJD 173 (1): 209–217 Control Cysteamine

68% MASI score reduction in melasma patients

by cysteamine (vs. control, BJD 2015)
15.1
16
11.9
10.6 68% MASI score
10.4
7.8 reduction
4.9
MASI-0
MASI-8
MASI-16
P = 0.27 P = 0.2 P = 0.02
Mansouri et al, 2015, BJD 173 (1): 209–217 Control Cysteamine

90% of patients noticed improvements of their

hyperpigmentation (JDT 2018)
Patient’s Viewpoint
Investigator’s Global
on Efficacy
Assessment
Placebo Cysteamine Placebo Cysteamine
No effect 60% 0% 35% 10%

(0% improvement)
Moderate 40% 45% 65% 40%
Significant 0% 55% 0% 50%
Complete 0% 0% 0% 0%
(100% improvement)
Study on 40 epidermal melasma patients

Daily application for 16 weeks: (1) wash face, (2) apply after 30 min, (3) wash off after 3 hours
Farshi et al, 2018, JDT 29:2, 182-189
Side effects are non significant when the protocol is

respected (JDT 2018)
None Mild Moderate Severe Side effects happen when …
• The face is washed just before the
Dryness 80% 20% 0% 0% application (minimum 1h interval to be
respected)
Erythema 65% 20% 15% 0% • Long exposure times (recommended: 15
minutes!)
Irritation 80% 15% 5% 0% • Concomittant use with other treatment
Itching 75% 25% 0% 0%

Side effects becomes very rare if …
• 15 minutes of exposure is respected
Burning 75% 15% 10% 0%
• The minimum 1h interval between
Dyspigment-
100% 0% 0% 0%
washing the face and the application of
ation Cysteamine is respected
Study on 40 epidermal melasma patients

Daily application for 16 weeks: (1) wash face, (2) apply after 30 min, (3) wash off after 3 hours
Farshi et al, 2018, JDT 29:2, 182-189
Mechanism of action
• Double enzyme inhibition: tyrosinase and peroxidase inhibitor

• Dopaquinone quenching: removing dopaquinone from the pathway
• Inhibition of Fenton-type reactions through iron and copper ion quenching
• Increase of intra-cellular glutathione
• Reduction of dark melanin in the stratum corneum into a lighter form through antioxidant
effect

How to use Cysteamine:
Attack treatment:
• once-daily evening
routine
• 12 weeks cycle treatment
Maintenance treatment:
• twice-weekly evening
routine
• As long as desired

Melasma
Before After 8 weeks
Courtesy of Dr. Behrooz Kasraee (Switzerland) © Scientis Pharma 2018 20

Patient under Kligman’s formula treatment Discontinuation of Pigmanorm and

(Pigmanorm cream) for the past 3 years treatment with Cysteamine for 4 months
The patient was

She has continued
under Kligman’s
Cysteamine use twice
formula treatment
weekly as
(Pigmanorm
maintenance therapy
cream) for 3
for the past 5 years.
years
She stopped No recurrence of

Kligman’s formula hyperpigmentation
treatment and with twice weekly
started application
Cysteamine for 4
months
After 5 years on Cysteamine maintenance

Photo-damaged skin
Before treatment After 8 weeks, 15min daily

Multiple lentigines / melasma on ageing skin

Courtesy of Dr. Joyce Lim (Singapore) © Scientis Pharma 2018 24


Post-inflammatory hyperpigmentation (Acne-induced)
PIH after acne, Before After 8 weeks, 15 min daily

Post-inflammatory hyperpigmentation
Post-acne PIH. Before After 8 weeks of treatment (15 min daily)

Freckle
before treatment After 12 weeks, 15min daily application

Courtesy of Dr. Joyce Lim © Scientis Pharma 2018 29
Melasma



Before treatment After 8 weeks, 15min Daily

Forearm hyperpigmentation
Before After 12 weeks, 15mins daily

Post-chemotherapy pigmentation
Before After 12 weeks, 15mins daily

The effect on semi-mucosa
The effect on lips hyperpigmentation after 19 days cysteamine treatment

Indications of treatment with cysteamine cream
Main indications
• Epidermal hyperpigmentation: epidermal melasma (not effective on

dermal type melasma)
• Mixed hyperpigmentation: Post-inflammatory hyperpigmentation,

hyperpigmentation caused by photo-damage
Miscellaneous
• Friction melanosis: hyperpigmentation in arm-pits, elbows and

knees
• Semi-mucosal hyperpigmentation: lip hyperpigmentation
• Peri-ocular hyperpigmentation: how to use?

Concomitant use with other products/procedures
• Topical retinoids, peelings, AHA’s: can be used if there is a 6-8 weeks

interval between starting the treatment with these agents and cysteamine
• Oral retinoids: no contra-indication, increase moisturizing, sun-protection
• Lasers, Micro-needling, cryotherapy: use cysteamine only when erythema

is completely subsided

Side effects
• Skin irritation:
o Concommittant use with other treatments
o Long Exposure times (recommended: 15 minutes!)
o The face is washed just before the application (minimum 1h
interval to be respected)
• Skin irritation becomes very rare if:

o 15 minutes of exposure is respected
o The minimum 1h interval between washing the face and the
application of Cysteamine is respected

SAFETY
• Biogenic molecule
• Long history of use in human
• Non-mutagenic and Non-carcinogenic activities

shown in numerous studies

Current cysteamine uses in medicine

Cysteamine Hydroquinone
Origin of
• Human biological • Non-human biological
molecule
• Tyrosinase inhibition
• Peroxidase inhibition
• Tyronase substrate
Mechanisms of • Intracellular glutathion increase
• Peroxidase substrate
action • Dopaquinone quenching
• Cytotoxicity
• Fenton-type reaction inhibition
• Reduction of melanin in corneum
• High depigmenting efficacy:
80% melanin synthesis reduction
77% melanin index reduction
Benefits • High depigmenting efficacy
68% MASI score reduction
• Biocompatible & well tolerated
• Anti-oxidation
• Mild irritation
Side effects • Ochronosis
(when not used as per instruction)
• Non-cytotoxic
• Melano-cytotoxic
• Non-mutagenic
Safety profile • Mutagenic?
• Non-carcinogenic
• Carcinogenic?
• Radioprotection agent


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I n t e n s i v e Pig m e n t C o r r e c t o r

Cysteamine Made in Switzerland

Current status of skin depimenting agents

• Hydroquinone has been used for

• Although still very controversial,

• Non-hydroquinone compounds such

© Scientis Pharma 2018 2

An effective and safe skin depigmenting agent

is intensely sought after by the healthcare community

© Scientis Pharma 2018 3

Cysteamine is the simplest aminothiol physiologically produced

© Scientis Pharma 2018 4

Cysteamine biosynthesis pathway in human cells

© Scientis Pharma 2018 5

Estimated values of cysteamine concentration in nutrients

© Scientis Pharma 2018 6

Courtesy of Dr. Larry Wu (Singapore) © Scientis Pharma 2018 7

In the 60s, Cysteamine was shown to be a depigmenting

In 1966, Chavin injected Cysteamine

In 1968, studies by Frenk,

but its odor prohibited its use

Chavin W. et al, 1966, Die Naturwissenschaften 53(16):413-414

80% reduction of melanin synthesis in B16 melanocytes

Qui L. et al, J. Invest Dermatol. 2000 Jan;114(1):21-7

Scientis Pharma developed a new technology

that significantly increases cysteamine stability

and reduces its odor

Usable Topically = Significantly reduced odor

© Scientis Pharma 2018 10

A first case series gave clues about

by Hsu et al, 2013

© Scientis Pharma 2018 11

A double-blind, randomized, vehicle-controlled

by Mansouri et al, 2015

© Scientis Pharma 2018 12

Other clinical trials have confirmed the results

"Significant efficacy in decreasing melanin content of

© Scientis Pharma 2018 13

77% melanin index reduction in melasma lesions

65.2 63.7 63.8 63.6

0 P = 0.79 P = 0.001 P = 0.0001

Week 0 Week 8 Week 16

Mansouri et al, 2015, BJD 173 (1): 209–217 Control Cysteamine

68% MASI score reduction in melasma patients

Mansouri et al, 2015, BJD 173 (1): 209–217 Control Cysteamine

90% of patients noticed improvements of their

Placebo Cysteamine Placebo Cysteamine

No effect 60% 0% 35% 10%

Moderate 40% 45% 65% 40%

Significant 0% 55% 0% 50%

Study on 40 epidermal melasma patients

Side effects are non significant when the protocol is

Itching 75% 25% 0% 0%

Study on 40 epidermal melasma patients

• Double enzyme inhibition: tyrosinase and peroxidase inhibitor

© Scientis Pharma 2018 18

How to use Cysteamine:

© Scientis Pharma 2018 19

Before After 8 weeks

Courtesy of Dr. Behrooz Kasraee (Switzerland) © Scientis Pharma 2018 20

Patient under Kligman’s formula treatment Discontinuation of Pigmanorm and

The patient was

She stopped No recurrence of