Safety and Efficacy Study of Combination Treatment With Excimer Laser, Clobex Spray, and Vectical Ointment in the Treatment of Psoriasis

Psoriasis is an inflammatory skin disease affecting approximately 2% of the population, and
approximately one-third of patients experience generalized psoriasis ( ). Current treatment
options include topical medications, ultraviolet B and oral psoralen with ultraviolet A
phototherapy, biologic agents, non-biologic systemic medications, and combinations of the
aforementioned. Phototherapy treatment, although effective for many patients, often is
inconvenient, requiring three treatments weekly for 2-3 months in order to achieve
significant improvement in a patient's psoriasis. The newer biologic medications, while
effective in many patients, work by systemic immunosuppression with increased risk of
malignancies, infections including tuberculosis and histoplasmosis, congestive heart
failure, lupus-like syndrome, demyelinating diseases, etc. In addition to side effects from
systemic immunosuppression, non-biologic systemic agents can have major organ toxicity as a
potential side effect including bone marrow suppression, liver toxicity, kidney toxicity,
etc.

Currently, we are at the threshold of a new era, where the possibility exists of treating
generalized psoriasis with absolute systemic safety and better efficacy than any systemic or
biologic agent. This possibility can only become a reality with a "perfect storm," in which
three storms collide. This "perfect storm" may achieve a result which no other therapy has
yet achieved: a Psoriasis Area Severity Index (PASI)75 response in 100% of patients after
only 4 weeks of therapy. The three "storms" include Clobex® spray, Vectical® ointment, and
the excimer laser machine XTRAC® Velocity.

Laser therapy (fiberoptically-directed monochromatic UVB light) targets only psoriatic
plaques. This allows much more aggressive phototherapy as compared to traditional
ultraviolet B and oral psoralen with ultraviolet A , which exposes non-involved skin as well
as psoriatic skin to UV light. With aggressive excimer laser therapy, it is well known that
psoriasis can improve significantly or clear in approximately ten sessions instead of the 30
to 40 sessions needed with regular full-body phototherapy to achieve clearance of the skin.
This dramatic difference is attributed to the fact that psoriatic lesions are able to
withstand a much higher dose of light than non-involved skin. Excimer laser therapy dosing
is determined by the maximum tolerance of psoriatic skin whereas full body UV therapy dosing
is determined by the MED (minimal erythema dose) of non-involved skin. Delivery of higher
doses subsequently results in faster clinical response and much greater clinical efficacy.
Hence, the new supra-erythemogenic phototherapy strategy results in a fewer number of
sessions needed for clearance ( ). The supra-erythemogenic phototherapy strategy involves
delivering UVB at a dose much greater than the minimal erythema dose (MED) (2). MED is the
traditional limit on how aggressively non-laser phototherapy can be conducted (UVB doses
beyond the MED will burn the patient).

In addition, excimer laser therapy results in no photo-damage to non-involved skin, given
its targeted application. The Photomedex XTRAC® Velocity is the latest version of the
excimer laser, which is 300-400% more powerful than its predecessor, the XTRAC® Ultra
machine. This increased power makes treatment of generalized, moderate to severe psoriasis
not only feasible but attractive. Time required for each treatment is decreased by
one-third, as compared to the XTRAC® Ultra which was previously the most powerful excimer
laser machine. XTRAC® Velocity is not yet available: it is scheduled to be introduced in a
few months. With XTRAC® Velocity, it is expected that generalized psoriasis patients with
10-30% total body surface involvement can be treated in 10-15 minutes and great improvement
can be achieved after approximately just ten laser treatment sessions.

Using the XTRAC® Ultra machine, in a pilot study of 9 patients receiving excimer laser
therapy twice weekly for 12 weeks, 77% of patients achieved a Psoriasis Area Severity Index
(PASI) 75 response ( ). In another study of 124 patients with stable plaque psoriasis (n =
124) covering less than 10% body surface area (BSA) were enrolled and 80 completed the study
( ). Seventy-two percent of patients achieved at least 75% clearing in an average of 6.2
treatments. Thirty-five percent achieved 90% clearing in an average of 7.5 treatments. In
another study of 40 patients treated with the excimer laser under a protocol determined by
MED of the involved skin, patients cleared in approximately half the number of treatments
compared to patients treated under a protocol where dosage was determined by MED of
non-involved skin ( ). However, aggressive laser therapy can also irritate the skin, and
Clobex® spray can be an ideal partner to enhance the efficacy and prevent irritation of the
skin from aggressive, supra-erythemogenic UVB irradiation. Moreover, beyond prevention of
skin irritation, there are additional merits of combining Clobex® spray with excimer laser.
These are the following:

- The very real possibility of synergistic efficacy where two very effective, external
therapeutic modalities are combined to possibly result in 100% of patients achieving
Psoriasis Area Severity Index (PASI) 75 by not week 12, but week 4 of therapy. If this
type of efficacy can be demonstrated, it would wipe out all competition in terms of
therapeutic efficacy.

- It is tedious to treat multiple small plaques with excimer laser therapy alone. The use
of Clobex® ® spray can help eliminate such small psoriatic plaques en masse.

- Laser therapy can help eliminate stubborn plaques still resistant to Clobex® ® spray
used BID for one month.

In a study of 1254 subjects treated with clobetasol propionate spray 0.05% as monotherapy
twice daily for four weeks, 35.7% of patients achieved clearance and 37.3% of patients were
almost clear using a 6-point target plaque severity scale. Additionally, at week 4, 80% of
subjects achieved target plaque severity (TPS) success, p<0.001. This was specifically
defined as a score of clear, almost clear using the TPS scale or an improvement in severity
of 2 grades. Topical steroids have the potential for adrenal suppression. However, when
topical steroids are used for one month or less at a time, this transient adrenal
suppression that may result is not a clinical problem.Furthermore, when using Clobex® spray,
patients are required to have a steroid-free interval after 4 weeks of therapy. The effect
of Clobex® spray can be maintained with a safe, non-steroidal topical medication, such as
Vectical. This newer Vitamin D topical agent can be used up to 210 g weekly, as compared to
topical calcipotriol (Dovonex®) which is limited to 100 g weekly, due to the better safety
profile of Vectical. Thus, Vectical can be used for patients with generalized plaque
psoriasis covering up to 35% body surface area. In addition, a comparative study in 250
patients demonstrated that Vectical caused significantly less skin irritation as compared to
calcipotriol ( ). Thus, with the imminent approval of Vectical, we are entering a new era
where a Vitamin D analogue can be used to treat patients with generalized psoriasis. With
these three "storms" gathering force, we propose the following study.

Inclusion Criteria:

1. Male or female subjects 18 years of age of older

2. Subjects should have ≥ 10%, but not more than 20% total body involvement of stable
plaque type psoriasis.

3. Subjects must have BMI < 30 and weigh less than 250lbs

4. Subjects must have Fitzpatrick Skin Type II or above (see Attachment A)

5. Subjects must be able to discontinue any topical therapy (other than emollients) or
received UVB phototherapy 2 weeks prior to starting the study.

6. Subjects must be able to discontinue any biologic or systemic agents or oral psoralen
with ultraviolet A 4 weeks prior to starting the study.

7. Subject is able to complete the study and to comply with study instructions.

8. Subject is capable of understanding and willing to provide signed and dated written
voluntary informed consent (and any local or national authorization requirements)
before any protocol specific procedures are performed.

9. Any additional diagnoses must, in the investigator's opinion, not preclude the
subject from safely participating in this study or interfere with the evaluation of
the subject's psoriasis

Exclusion Criteria:

1. Subject is younger than 18 years of age.

2. Subject has less than 10% or greater than 20% body surface involvement of his/her
psoriasis.

3. History of known or suspected intolerance to any of the ingredients of the
investigational study product.

4. Subject has a photosensitivity disorder (such as lupus, etc.) or a history of
clinically significant photosensitivity.

5. Subjects possess other diagnoses that, in the investigator's opinion, preclude
him/her from safely participating in this study or interfere with the evaluation of
the subject's psoriasis.

6. Subject is not willing to discontinue topical treatment (other than emollients) or
UVB phototherapy for 2 weeks prior to starting the study

7. Subject is not willing to discontinue biologic or systemic agents or oral psoralen
with ultraviolet A for 4 weeks prior to starting the study.

8. Subject has psoriatic involvement only on the hands, feet, or scalp.

9. Subject has been diagnosed with unstable or non-plaque forms of psoriasis, including
guttate, erythrodermic, exfoliative, or pustular psoriasis.

10. Subject has a history of keobnerization phenomenon

11. Subject has keloids or past history of keloid formation

12. Subject has melanoma or past history of melanoma

13. Subject has active (cutaneous) invasive non-melanoma skin cancer (NMSC)

14. Subject is determined not be a candidate for phototherapy by the investigator

15. Subject has used other investigational drugs within 4 weeks prior to the study

16. Subject is known, or suspected of being unable to comply with the study protocol