Androgenetic alopecia Dermatology CONFIDENTIAL

(not for distribution)

P-3074
Topical finasteride 0.25%
Fig 1. Molecular
structure of finasteride.

P-3074, a topical finasteride spray solution is in EU Mode of action

registration procedure for the treatment of Androgenetic
Alopecia (AGA). • Finasteride (C23H36N2O2) is a competitive and specific
inhibitor of type II 5α-reductase, an intracellular enzyme
that converts the androgen testosterone into
Common use: Androgenetic alopecia dihydrotestosterone (DHT).

Androgenetic alopecia, or male pattern baldness, is
characterized by progressive patterned hair loss from the scalp
and is recognized as a physically and psychologically untoward
medical condition. 1
The basis of androgenetic alopecia in men is a progressive
decrease in the density of terminal hair and a concurrent
increase in the density of short, non-pigmented hair. This effect
is attributed to miniaturization of the hair follicle, which is
associated with a substantial reduction in hair diameter. 2
Although the mechanism of these changes has not been
definitively established, male pattern baldness is known to
depend on the presence of the androgen dihydrotestosterone
(DHT)3, which is formed by through the action of the Type II 5-
α reductase isoenzyme, and on genetic predisposition. In the
scalp of men suffering from AGA, increased rates of
conversion of testosterone into DHT have been detected.4
A topical finasteride formulation, in comparison with the
marketed oral tablet, might potentially reduce some of the
systemic side effects related to the mechanism of action of
finasteride, due to expected preferential inhibition of the
5-α reductase enzyme in the scalp5 maintaining the same
efficacy to increase hair growth and prevent further hair loss.
• This novel formulation contains hydroxypropyl chitosan
(HPCH) as an excipient, which:
– maintains a balanced amount of finasteride at the
surface of the scalp, for enough time to allow the active
compound to penetrate through the skin layers5,
– allows finasteride to act on the scalp skin follicular
portion of the bulb6,
– promote a cutaneous depot of finasteride in the region of
hair bulbs, thus minimizing systemic absorption even
after repeated treatments7.

1. Stough D, et al. Mayo Clin Proc. 2005; 80: 1316-1322. 2. Whiting DA. J Am Acad Dermatol. 2001; 45 (Suppl):S81-S86. 3. Kaufman KD. Mol Cell Endocrinol.
2002; 198: 89-95. 4. Whiting DA. Int J Dermatol. 1998; 37: 561-566. 5. Caserini M, et al. Int J Clin Pharmacol Ther. 2014;52(10):842-9. 6. Caserini M et al. Int J
Clin Pharmacol Ther. 2016;54(1):19-27. 7. Monti D, et al. J Pharm Sci. 2014; 103: 2307-2314.
 Androgenetic alopecia
Project status*
March 2012 Phase I
pharmacokinetics of topical vs oral
finasteride in male volunteers with
AGA. Completed (PM 1024).
May 2013 Phase I
pharmacodynamics study of topical vs
oral finasteride in male volunteers
with AGA. Completed (PM 1227).
October 2014 Phase IIa dose-
response, pharmacodynamics and
pharmacokinetic study of topical
finasteride vs placebo in male
subjects with AGA. Completed (PM
1332).
October 2016 Phase I
photosensitization study in healthy
male volunteers. Completed (PM
1542).
November 2018 Phase III efficacy
and safety study comparing topical
finasteride with placebo vehicle and
oral finasteride in male subjects with
mild-to-moderate vertex male pattern
hair loss. Completed (PM 1541).
*Information updated on September 2019.
GMBFIN2186 September 2019
Dermatology Product profile
Clinical evidence: Phase III study
A multicentre, randomized, double-blind, parallel-group, controlled study, to assess the
efficacy and safety of p-3074 cutaneous spray, solution, in the treatment of male pattern
baldness
EudraCT number 2015-002877-40
https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-002877-40/results
Objective: The primary objective of this pivotal phase III study was to determine whether a daily
treatment of 24 weeks with P-3074, increased hair count in men with androgenetic alopecia
(AGA) compared to vehicle.
Methods:
• Multicentre, randomised, double-blind, double-dummy, parallel-group, controlled study of P-
3074 in men with AGA.
• 458 male patients between the ages of 18 and 40 years with mild to moderate vertex male
pattern hair loss were enrolled in the study. Patients were randomised to receive either active
P-3074 (finasteride 0.25%) + oral finasteride placebo (P), or vehicle + P, or active oral FNS
(finasteride 1 mg tablet) + vehicle, all of them once daily in the morning.
• Patients were treated over a 24 week period with the assigned treatment regimen, with
assessments and study procedures performed at weeks 4, 8, 12, and 24. A follow-up visit
took place at week 28.
Results:
• Efficacy results: In the primary endpoint, P-3074 + P showed statistically significant
differences versus vehicle + P in hair growth, as assessed by Target Area Hair Count
(TAHC) in the vertex at 24 weeks. The LS mean change from baseline over placebo was
13.6, which was statistically significant with a p-value <0.001. For the secondary endpoints,
P-3074 + P showed statistically significant differences versus vehicle + P in hair
growth at 12 weeks as well (p<0.001) and in the investigator assessment of patient hair
growth/loss change from baseline at week 24 (p<0.001).
• Safety results: Overall, P-3074 + P was safe and well tolerated. The overall rate of
treatment emergent adverse events (TEAEs) in the P-3074 + P group (41.1% patients) was
similar to vehicle + P (42.0%) and lower than the oral FNS + vehicle group (48.8%). The
majority of TEAEs was of mild or moderate severity across all treatment groups.
Conclusions: Overall P-3074 was efficacious, safe, and well tolerated. There were
statistically significant differences in hair growth for P-3074 compared to placebo at both
12 and 24 weeks, with similar efficacy results in the oral FNS + vehicle group.