Male Alopecia: Treatment Update Ken Washenik MD PhD Bosley / Aderans Research Institute New York...
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Transcript of Male Alopecia: Treatment Update Ken Washenik MD PhD Bosley / Aderans Research Institute New York...
Male Alopecia: Treatment Update
Ken Washenik MD PhD Bosley / Aderans Research Institute
New York University School of Medicine
Disclosure:• Bosley / Aderans Research
- Employee, salary, stock options, royalties
• Allergan - Advisor
• Johnson and Johnson Healthcare Products- Clinical investigator
• Merck – Speaker Bureau
• Boards of Directors- North American Hair Research Society- Cicatricial Alopecia Research Foundation- Hair Foundation
• Off-label use discussed
Dihydrotestosterone is the principal androgen causing hair loss in men, but probably not in women
Androgens and Follicle Miniaturization in Androgenetic Alopecia
Targets for Pharmacologic Therapy in Androgenetic Alopecia
• The follicular miniaturization caused by the shortening of the anagen phase- Anagen induction and prolongation
agents- Minoxidil
Increased Scalp Coverage with Minoxidil Solution
5%
minox
2%
minoxVehicle
Frontal1 51% 42% 13%
Vertex2 54% 38% 17%
Patients with at least slight increase in scalp coverage judged by photographic review at 48 weeks
1Olsen EA et al AAD 2003; Poster #397 2Olsen EA et al JAAD 2002;47:377-385
Minoxidil: Mechanism of Action
• Not related to androgens
• Direct stimulator of follicular growth (VEGF and prostaglandin synthase)1
• Anagen induction and prolongation
1Messenger and Rundegren. Br J Dermatol 2004;150:186-94
Targets for Pharmacologic Therapy in Androgenetic Alopecia
• The follicular miniaturization caused by the shortening of the anagen phase- Anagen induction and prolongation
agents- Minoxidil- Prostaglandin analogs / prostamides
Prostaglandins and Hair Growth
• Latanoprost Solution (Xalatan)
- Eye drops for glaucoma
- Prostaglandin F2analog
- 77% developed increased eyelash growth (317 patients)
- Applied once daily for 4 months (avg)
Demitsu et al JAAD 44:721-723 (2001)
Uno et al. Acta Derm Venereol 82: 7-12 (2002)
Prostaglandins and Hair Growth
Approved as a stimulator of eyelash growth in 2008
• 0.3 % bimatoprost ophthalmic solution, qD x 16 wks
Law SK. Clin Ophthalmol. 2010; 4: 349–358.
http://latisse.com/ClinicalTrialGallery.aspx?state=24
Prostaglandins and Hair Growth
• Phase I trial of topical bimatoprost in MPHL and FPHL underway
http://www.clinicaltrials.gov
Targets for Pharmacologic Therapy in Androgenetic Alopecia
• The follicular miniaturization caused by the shortening of the anagen phase
• Dihydrotestosterone (DHT)- Synthesis inhibitors
- Finasteride
Mechanism of Action of Finasteride
O
OH
Testosterone
NADPH
5-ReductaseType II
O
OH
DHT
FinasterideO NH
CONHC(CH3)3
Decreased 60 – 70%
Global Photographic Assessment
- 10% lost hair
- 48% gained hair
90% gained or did not lose hair
Increase
No Change
- 42% no loss
Vertex Data
Finasteride 1 mg for 5 years Men 18-41 years old
European Journal of Dermatology. 2002; 12: 38-49
Photographic Assessment
Finasteride 1 mg
Targets for Pharmacologic Therapy in Androgenetic Alopecia
• The follicular miniaturization caused by the shortening of the anagen phase
• Dihydrotestosterone- Synthesis inhibitors
- Finasteride- Dutasteride (not approved for AGA)
Dutasteride: A Dual 5 -Reductase Inhibitor
• Inhibits type 1 and 2 enzymes- Lowers DHT by ~90%
• FDA approved for prostate indication (BPH)
• Six month Phase II study indicated better efficacy than finasteride*
• Long 5 week half life
• Safety data consistent with DHT reductionPossibility of prolonged reduction in sperm count
added to label*Olsen et al. J Am Acad Dermatol. 2006 Dec;55(6):1014-23
Eun et al. J Am Acad Dermatol 2010;63:252-8
Eun et al. J Am Acad Dermatol 2010;63:252-8
Eun et al. J Am Acad Dermatol 2010;63:252-8
Dut (N=73) Plac (N=75)
Dutasteride Phase III Study
Eun et al. J Am Acad Dermatol 2010;63:252-8
Investigator Assessment: Slight, Moderate or Great Increase
61.6% Dutast 20.0% Placebo
Safety: Finasteride
FIN 1MG(N = 945)
1.8
1.3
Percentage of Patients :
Decreased Libido
Erectile Dysfunction
Phase III 1 Year Studies
1.3
0.7
PBO(N = 934)
Phase III 5 Year Studies (N = 323) (N = 23)
Decreased LibidoErectile Dysfunction
0.30.3
00
Controversy Over Reports of Persistent Sexual Side Effects
• Post Marketing reports of persistent sexual side effects
• Label indicating these reports in Sweden and UK
• Two recent manuscripts discussing these types of reports in the Journal of Sexual Medicine
• Class action lawsuit in CanadaJ Sex Med.1743-6109.2010 and 1743-6109.2011
Update on Medical Treatment
• Anagen prolongation agents- Bimatoprost in clinical development for MPHL
and FPHL- 5% minoxidil foam in clinical trials for FPHL
• 5 alpha reductase inhibitors- Dutasteride approved for MPHL in Korea- Controversy concerning reports of persistent
side effects
Emerging Therapies
• Follicle Regeneration- Follicle Cell Transplantation
Important Cells for Follicle Regeneration
Epidermal Cells
Dermal Cells
Inducer Responder
Isolate, Multiply and Inject Trichogenic Cells
Clinical Trial Status of Follicle Cell Transplantation
• Phase I completed in UK in 2008
• Phase II testing currently underway for male pattern hair loss (MPHL) and FPHL in the US
• Iterative series of protocols enrolling 20 – 40 subjects per protocol
• Only early interim data available
Baseline Week 12
Macrophotographic Assessment
Unpublished data: Aderans Research Institute
+33.7% Total hair count (+115)+53.8% Terminal hair count (≥ 30µm)+10.7% Vellus hair count (<30 µm)
Excision 54 Weeks
Macrophotographic Assessment
Unpublished data: Aderans Research Institute
Thank You