Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and
dysphagia and if left untreated can promote the development of laryngeal cancer. More than
20% of the United Stated population suffer from LPR, yet there is no effective medical
therapy. Proton pump inhibitors (PPIs), which inhibit gastric acid production but do not
prevent reflux events, continue to be prescribed for LPR despite their poor efficacy for this
patient population, high cost ($26 billion/year), and associated risks. Pepsin, detected in
the airway of these patients and now known to cause laryngeal inflammation and promote
disease independent of gastric acid, is a key therapeutic target. We report preclinical
studies of select HIV inhibitors that bind to and inhibit pepsin and thus hold promise for
the treatment of LPR. In support, a very low incidence of LPR was found in patients taking
these drugs compared to the general population. HIV inhibitors are ideal drugs to repurpose
because they target a foreign virus. Thus, a repurposing approach can be used to safely
perform proof of concept testing of the efficacy of a pepsin inhibitor for LPR. The Specific
Aim of this project is to perform a 12-week randomized, double-blind, placebo-controlled
clinical trial to assess the efficacy of fosamprenavir/Lexiva for LPR. Lexiva will be used at
the FDA approved, manufacturers recommended dose for HIV for 12 weeks in medically refractory
patients with clinically diagnosed moderate/severe LPR and combined multi-channel
intraluminal impedance - pH (MII-pH) confirmed laryngeal reflux events. Routine clinical
outcome measures for LPR (Reflux Symptom Index and Reflux Finding Score) will be documented
pre- and post-treatment with Lexiva (n = 52) and placebo (n = 52). Saliva will be collected
pre- and post-treatment for both pepsin protein analysis and kinetic activity assay to
compare with clinical measures. There is currently no effective medical therapy for LPR and
pepsin is the key therapeutic target. Identification of an FDA approved drug which inhibits
pepsin allows for a clinical trial to determine efficacy using a faster and safer repurposing
approach to address a significant gap.