1. Male Alopecia: Treatment Update
Ken Washenik MD PhD Bosley / Aderans Research Institute New York University School of Medicine

2. 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

3. Androgens and Follicle Miniaturization in Androgenetic Alopecia
Dihydrotestosterone is the principal androgen causing hair loss in men, but probably not in women

4. Targets for Pharmacologic Therapy in Androgenetic Alopecia
The follicular miniaturization caused by the shortening of the anagen phase
Anagen induction and prolongation agents
Minoxidil

5. Increased Scalp Coverage with Minoxidil Solution5%
minox 2%
Vehicle
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:

6. 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

7. 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

8. Prostaglandins and Hair Growth
Latanoprost Solution (Xalatan)
Eye drops for glaucoma
Prostaglandin F2a analog
77% developed increased eyelash growth (317 patients)
Applied once daily for 4 months (avg)
Demitsu et al JAAD 44: (2001)
Uno et al. Acta Derm Venereol 82: 7-12 (2002)

9. 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.

10. Prostaglandins and Hair Growth
Phase I trial of topical bimatoprost in MPHL and FPHL underway

11. Targets for Pharmacologic Therapy in Androgenetic Alopecia
The follicular miniaturization caused by the shortening of the anagen phase
Dihydrotestosterone (DHT)
Synthesis inhibitors
Finasteride

12. Mechanism of Action of FinasterideOH
Testosterone
NADPH
5-Reductase
Type II
DHT
Finasteride N H
CONHC(CH3)3
Decreased 60 – 70%

13. Global Photographic Assessment
Finasteride 1 mg for 5 years Men years old
- 48% gained hair
90% gained or did not lose hair
Increase
- 10% lost hair
No Change
- 42% no loss
Vertex Data
European Journal of Dermatology. 2002; 12: 38-49

14. Photographic Assessment
Finasteride 1 mg

15. 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)

16. Dutasteride: A Dual 5 a-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 reduction
Possibility of prolonged reduction in sperm count added to label
*Olsen et al. J Am Acad Dermatol Dec;55(6):

17. Eun et al. J Am Acad Dermatol 2010;63:252-8

18. Eun et al. J Am Acad Dermatol 2010;63:252-8

19. Dut (N=73) Plac (N=75)
Eun et al. J Am Acad Dermatol 2010;63:252-8

20. Dutasteride Phase III Study
Investigator Assessment: Slight, Moderate or Great Increase
61.6% Dutast % Placebo
Eun et al. J Am Acad Dermatol 2010;63:252-8

21. Safety: Finasteride Percentage of Patients : Decreased Libido
Erectile Dysfunction
Phase III 1 Year Studies
1.3
0.7
PBO
(N = 934)
FIN 1MG
(N = 945)
1.8
1.3
Phase III 5 Year Studies
(N = 323)
(N = 23)
Decreased Libido
Erectile Dysfunction
0.3 21

22. 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 Canada
J Sex Med and

23. 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

24. Emerging Therapies
Follicle Regeneration
Follicle Cell Transplantation

25. Important Cells for Follicle Regeneration
Epidermal Cells
Dermal Cells
Inducer
Responder

26. Isolate, Multiply and Inject Trichogenic Cells

27. 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 – 40 subjects per protocol
Only early interim data available

28. Macrophotographic Assessment
Baseline
Week 12
Unpublished data: Aderans Research Institute

29. Macrophotographic Assessment
Excision
54 Weeks
+33.7% Total hair count (+115)
+53.8% Terminal hair count (≥ 30µm)
+10.7% Vellus hair count (<30 µm)
Unpublished data: Aderans Research Institute

30. Thank You