The only drug in clinical trials for prevention of cold sores is squaric acid dibutylester (SADBE, available at square-immune.com). It is being developed as a drug by SquareX Pharmaceutical Corporation.
Squaric acid dibutylester (SADBE).
Dosing: Topical. Apply to the inner aspect of the upper arm (the part facing the chest), not to a cold sore or lesion. One dose every 3 months. Can be taken during or between outbreaks.
Efficacy:
Duration: Not tested.
Severity of outbreaks: Not reported.
Prevention: Reduces number of outbreaks by 62% (0.231 in the treatment group versus 0.610 in the placebo group) in the period from 43 to 121 days after a single dose to the arm.
Mechanism of Action:
SADBE causes a delayed-type hypersensitivity response in the skin at the drug application site, and this, after an immune training period similar to a vaccine, which the data suggests takes 3 to 6 weeks to happen, causes a shift in the immune responso to the herpes virus from an antibody to a T-cell response and from what is called a type 2 immune response (interleukin-5) to a type-1 response (interferon gamma). The cellular and type 1 immune response is more effective than an antibody and type 2 response against viruses in general and herpes virus in particular.
Expression of 14 immune related genes was found to correlate with fewer cold sore outbreaks in persons infected with HSV-1, and dosing patients with one dose of SADBE was found to improve expression of all 14 genes by immune cells 8 weeks after one dose to the patients.
Side Effects: SADBE often causes a mild rash with mild itching, pain, and redness on the skin at the drug application site. That is why it is advisable to apply it to the arm and not to a lesion. Dosing on the arm only was found in two clinical trials to be effective in reducing number of outbreaks compared to placebo.
Availability:
SADBE is not approved as a drug and therefore not generally available. A 2% SADBE solution (the formulation used in clinical trials) can be purchased online as a cosmetic from square-immune.com.
References:
Chang ALS, Honari G, Guan L, Zhao L, Palli MA, Horn TD, Dudek AZ, McTavish H.
A phase 2, multi-center, placebo-controlled study of single dose squaric acid dibutyl ester (SADBE) to reduce frequency of outbreaks in subjects with recurrent herpes labialis.
Journal of the American Academy of Dermatology 2020 Dec;83(6):1807-1809. PMID: 32289388 DOI: 10.1016/j.jaad.2020.04.021. https://pubmed.ncbi.nlm.nih.gov/32289388/
McTavish H, Zerebiec KW, Zeller JC, Shekels LL, Matson MA, Kren BT.
Immune characteristics correlating with HSV-1 immune control and effect of squaric acid dibutyl ester on immune characteristics of subjects with frequent herpes labialis episodes.
Immunity, Inflammation and Disease 2019;7(1):22-40. PMID: 30756512 PMCID: PMC6416766 DOI: 10.1002/iid3.241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416766/
McTavish H, Kimball A, Horn TD. Immunotherapy of recurrent herpes labialis with squaric acid.
JAMA Dermatology 2017;153:828-829. PMID: 28538997 PMCID: PMC5817593 DOI: 10.1001/jamadermatol.2017.0725. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817593/
SquareX Pharmaceutical Corporation website: https://squarex-pharma.com