Low-dose Oral Thimerosal for the Treatment of Oral Herpes: Clinical Trial Results and Improved Outcome After Post-hoc Analysis

Stephen W Mamber, Thomas Hatch, Craig S Miller, John V Murray, Cynthia Strout, John McMichael, Stephen W Mamber, Thomas Hatch, Craig S Miller, John V Murray, Cynthia Strout, John McMichael

Abstract

Background: Thimerosal (TML) is an organomercury antimicrobial. Low doses (1/250th of the amount in a typical vaccine dose) may promote an antiviral immune response. Low-dose TML (BTL-TML) was evaluated for safety and efficacy against herpes labialis in two FDA-approved, randomized, double blind, placebo-controlled clinical trials.

Methods: BTL-TML was evaluated in a Phase IIa trial for its ability to block progression to lesion in subjects with recurrent oral herpes caused by dental trauma. Subjects were administered BTL-TML or a saline control over a 7-day period. In a Phase IIb trial, BTL-TML was evaluated for its ability to block progression to lesion over a 7-day period in subjects with herpes lip infections induced by exposure to ultraviolet (UV) radiation.

Results: Progression to lesion post-dental procedure was prevented in 54.5% (12/22) TML subjects versus 22.2% (2/9) control subjects (p = 0.106). Progression to lesion post-UV irradiation was blocked in 47.8% (11/23) BTL-TML treatment subjects and 42.8% (6/14) control subjects. A post-hoc analysis yielded 52.2% (12/23) BTL-TML subjects with no progression to lesion versus 28.6% (6/21) control subjects with no progression (p = 0.099). There were no significant differences in adverse effects between treatment and control groups in either trial.

Conclusions: Neither clinical trial showed a statistically significant effect of BTL-TML on progression to lesion. However, the post-hoc analysis suggested there is a 48-hour period following UV radiation exposure during which the anti-herpes activity of antivirals such as BTL-TML is reduced. Accordingly, BTL-TML may have promise in subsequent, properly designed and powered clinical trials.

Trial registration: ClinicalTrials.gov NCT01308424 NCT01902303.

Keywords: HSV1; cold sores; herpes simplex labialis; oral herpes; oral treatment; thimerosal.

Conflict of interest statement

Declaration of Conflicting Interests: Hatch and McMichael are employees of Beech Tree Labs, the sponsor of both the P2a and P2b studies.

Figures

Figure 1.
Figure 1.
Average pain scores for the treatment and control groups, treatment days 0-7. Black = BTL-TML, grey = saline control.
Figure 2.
Figure 2.
Prevention of progression to lesion from post-hoc analysis of self-assessment data (>48 hours through 7 days post-UV exposure).

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