Researchers Stop Vitiligo Progression! New hope for millions worldwide. Dr. Igor Korobko, Chief Scientific Director of the non-profit Vitiligo Research Foundation (http://www.vrfoundation.org/), has reported a major breakthrough in vitiligo therapy development at the 10th EADV Spring Symposium in Krakow, Poland. Data released on May 24, 2013 from VRF's preclinical study of a Pharmsyntez drug, sold under the trademark Neovir, has shown positive results in arresting vitiligo lesion progression in 73.3 percent of patients with an active form of vitiligo. In four of the 60 patients taking part in the study, vitiligo lesions re-pigmented significantly. Sodium oxodihydroacridinylacetate (ODHAA) is the active ingredient in Neovir, with an immunomodulatory capacity that is currently being used to normalize impaired immune system functions for various conditions. Serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were used as predictive and end-point markers during the trials. The treatment was well tolerated by patients, and no side effects were observed. Researchers from the VR Foundation study did not compare the drug with a control placebo or other treatment modality, and it is, as yet, unclear how long the effects will last, though there are signs that for many patients, it could be up to a year or more. It may also be used to prevent vitiligo relapse after stopping its progression with an annual administration of the drug. It is also not clear yet whether the drug will work for segmental vitiligo, which is often seen as a distinctly different form of the disease. This study, and others on immune system drugs, will perhaps be the most closely watched items in the Vitiligo Research Foundation’s drug re-purposing research activities. The Foundation’s CEO, Yan Valle, noted that today scientists know the molecular cause of 4,000 diseases, but treatments are available for only 250 of them. Systematic drug development is lagging behind for many rare and complex diseases. Drug re-purposing offers some effective and cost-efficient solutions. Mr. Valle went on to add, “We are focused on off-label testing of approved drugs that are already on the market, and thus are already available to patients immediately. Neovir is cheaply available without prescription across the former Soviet Union, it is very affordable and has an excellent long-standing safety profile,”. At the moment it is still unclear when this drug will be available in the United States or European Union. Coming a month before World Vitiligo Day (http://25june.org/) on June 25, it is another positive sign that there is hope on the horizon for vitiligo sufferers.

1. Igor V. Korobko,1 Konstantin M. Lomonosov1,2
1 VR Foundation, New York, NY, USA
2 Department of skin and venereal diseases, I.M. Sechenov First
Moscow State Medical University, Moscow, Russia

2. ABSTRACT
INTRODUCTION & OBJECTIVES
Vitiligo is a pigmentary disorder affecting around 0.5% of the world population.
Recent vitiligo treatment armory is quite scanty, and little efforts are undertaking to
bring novel treatment options to patients, most likely due to a non-life threatening
nature of the disease. Yet vitiligo often results in a social repulsion and psychological
burden thus demanding for novel treatments to cope with this condition. Stopping
depigmentation progression is a prerequisite for subsequent successful
repigmentation when dealing with active vitiligo. Although mechanisms of vitiligo
pathogenesis are far from being completely understood, disease progression is most
likely linked to autoimmune processes. Sodium oxodihydroacridinylacetate
(ODHAA) is a substance with immunomodulatory activity which is used to
normalize impaired immune system functions under various conditions. The aim of
the study was to investigate efficacy of ODHAA in stabilizing active vitiligo.
MATERIALS & METHODS
Sixty patients with active non-segmental vitiligo were treated with ODHAA (10
intramuscular injections every other day). Vitiligo progression was assessed in 1, 3, 6
and 12 months after treatment. Serum tumor necrosis factor a (TNFa) and
interleukin-6 (IL-6) levels were measured prior and after treatment by IVD-certified
ELISA.

3. ABSTRACT (continued)
RESULTS
After treatment with ODHAA, in 44 out of 60 patients (73.3%), cessation of vitiligo
activity has been observed, with disease remaining stable in 12 month follow-up. In 4
patients, some repigmentation of depigmented lesions was seen. The treatment was
well tolerated by the patients, and no side effects were observed. Absence of other
autoimmune diseases, younger age and shorter disease duration correlated with
favorable treatment outcome. In addition, serum IL-6 level prior the treatment
emerges as a prognostic factor to predict successful arresting disease progression by
ODHAA.
CONCLUSIONS
Our results enlighten ODHAA as a novel efficient agent for active vitiligo treatment
and warrant its further investigation in a larger study.

4. Stop disease
progression
Induce
repigmentation
Prevent
recurrence
Systemically acting treatments:
Phototherapy – lengthy treatment with strict schedule
Steroids – side effects
Experimental treatments – side effects, incomplete efficacy

5. Stop disease
progression
Induce
repigmentation
Prevent
recurrence
?Need for convenient side
effect free treatments

6. N-acridone acetic acid: sodium or N-methylglucamine salt

7. •Long-term officially approved use in medicine
•Excellent safety profile
Mode of action:
•Immunomodulating compound, interferon inducer
Official indications:
•Viral infections
•Immunodeficiency
•Oncological diseases
•Multiple sclerosis

8. •Long-term officially approved use in medicine
•Excellent safety profile
Mode of action:
•Immunomodulating compound, interferon inducer
Official indications:
•Viral and bacterial infections
•Rheumatoid and systemic connection tissue diseases –
suppressing autoimmune reactions, anti-inflammatory

9. • alterations in blood immunophenotype (CD3+,
CD4+, CD8+, CD19+; CD4+/CD8+)
• positive results in experimental treatment of
diseases with autoimmune etiology:
- rheumatoid arthritis;
- lupus erythematosus;
- psoriasis,
which were accompanied by normalization of
immunophenotype in peripheral blood

10. Autoimmune reaction
Vitiligo activity
Acridone acetic acid
Normalizing immune
system functions,
including
autoimmune
processes
Acridone acetic acid Active vitiligo
?

11. Aim:
to evaluate efficiency of acridone acetic acid, sodium salt,
in stopping active nonsegmental vitiligo progression
Study design:
• pilot uncontrolled study;
• 60 patients with nonsegmental vitiligo were treated by
10 i.m. injections (250 mg each) every 48 hrs;
• serum IL-6, IL-8, TNFa and serum, spontaneous and
induced IFNa and IFNg levels were determined prior to
and after the treatment;
• disease activity was assessed in 1, 3, 6 and 12 months
after treatment.

12. Gender: females – 38 (63.3%); males - 22 (36.7%)
Age: 34.3±10.2 years (range 18 – 64)
Disease duration: 13.6±8.7 years (range 1 – 36)
Vitiligo type: localized – 46 (76.7%), generalized – 14 (23.3%)
Leukotrichia: 6 patients (10%)
Family history: 7 patients (11.7%)
Co-morbid autoimmune diseases: 6 patients (10%)

13. 38
15
7
42
15
3
44
16
43
1
16
1 month
12 months
3 months
6 months
stable disease
active disease
no data
44 out of 60
patients
(73.3%)
achieved
long-term
disease
stabilization

14. Presence of other autoimmune pathologies
Р=0.038, OR=7.0, 95% CI 1.14-42.97; n=6
Lower age
32.5±10.1 years, n=44 versus 39.2±8.8 years, n=16, Р=0.0219
Age under 35: Р=0.0189, OR=5.2, 95% CI 1.30-20.84
Age under 40: Р=0.0039, OR=6.48, 95% CI 1.86-22.61
Shorter disease duration
12.1±8.0 years, n=44 versus 13.6±8.7 years, n=16, Р=0.0234

15. High IL-6 level before treatment
Serum IL-6 above normal level
(>5.9 pg/ml)
Р=0.0009, OR=25.8, 95% CI 2.8-239
Detectable (>2 pg/ml) serum IL-6
Р=0.0005, OR=13.7, 95% CI 2.97-63
0
5
10
15
20
25
30
35
40
45
IL-6 <2 pg/ml IL-6 >2 pg/ml
0
5
10
15
20
25
30
35
40
45
50
IL-6 < Ref IL-6 > Ref

16. 0
5
10
15
20
25
30
35
0 20 40 60 80
Age
Low IL-6 (<2 pg/ml)
Ageofdiseaseonset
0
5
10
15
20
25
30
35
40
0 20 40 60 80
High IL-6 (>2 pg/ml)
Ageofdiseaseonset
Age
stable disease active disease

17. In the preliminary study, sodium
oxodihydroacridinylacetate showed high efficiency
in achieving long-term stabilization of
nonsegmental vitiligo
Lower age, shorter disease duration, lack of other
autoimmune diseases, and low serum IL-6 level are
predictors of good response
Further controlled studies are required to prove it
efficiency and further validate prognostic factors

18. Sodium oxodihydroacridinylacetate (and other salts of
acridone acetic acid) emerges as novel treatment for
vitiligo
•efficient and long-term cessation of disease
activity;
•excellent safety profile

19. Identified clinical parameters permit prediction of
response:
• rational selection of treatment;
• personalized approach

20. Potential to apply for vitiligo recurrence prevention:
• none presently exists.

21. I.M. Sechenov First Moscow
State Medical University
Vitiligo Research Foundation
(VR Foundation)