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

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

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% 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;47:377-385

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 F2a analog 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 OH Testosterone NADPH 5-Reductase Type II DHT Finasteride N H CONHC(CH3)3 Decreased 60 – 70%

Global Photographic Assessment Finasteride 1 mg for 5 years Men 18-41 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

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 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. 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

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

Dutasteride Phase III Study Investigator Assessment: Slight, Moderate or Great Increase 61.6% Dutast 20.0% Placebo Eun et al. J Am Acad Dermatol 2010;63:252-8

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

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.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

Macrophotographic Assessment Baseline Week 12 Unpublished data: Aderans Research Institute

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

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