Revive Therapeutics Ltd. has announced a strategic collaboration with Attwill Medical Solutions LP (AMS) to advance the clinical and commercial development of a novel lyophilized formulation of Bucillamine, positioning the oral thiol-based drug as a potential treatment for long COVID and other inflammatory conditions.
Enhanced Formulation Shows Promising Solubility Improvements
The University of Waterloo research team has successfully improved Bucillamine's solubility through lyophilization, resulting in more than double enhancement of solubility compared to standard formulations. This breakthrough could unlock the therapeutic utility of Bucillamine across multiple indications, according to Michael Frank, CEO of Revive Therapeutics.
"The formulation development of our novel lyophilized formulation of Bucillamine at the University of Waterloo is near complete, and we are now entering into the next phase of our product development cycle and preparing for a clinical trial," Frank stated.
Manufacturing Partnership Accelerates Clinical Timeline
AMS, one of the largest medical lyophilizers in the U.S., operates cGMP facilities with dryers capable of lyophilizing volumes ranging from 1 to 2,000 liters per cycle. The collaboration will support technology transfer from the University of Waterloo to AMS, followed by GMP manufacturing for clinical trials. Revive expects to have its novel lyophilized Bucillamine ready for clinical evaluation in 2024.
Long COVID Represents Significant Market Opportunity
The CDC estimates that 7.5% of U.S. adults currently experience long COVID symptoms. Harvard University economics professor David Cutler estimates the total economic cost of long COVID could reach $3.7 trillion, highlighting the substantial unmet medical need.
Revive is preparing a clinical package that includes a proposed Phase 2/3 clinical protocol for long COVID to present to the FDA and international health regulatory bodies. This initiative builds upon existing data from the company's previous Phase 3 clinical trial in mild to moderate COVID-19.
Previous Trial Data Supports Development Strategy
In July 2023, Revive announced results from its Phase 3 study evaluating oral Bucillamine in patients with mild to moderate COVID-19. Under the study's primary endpoint measuring hospitalization or death through Day 28, there were no deaths and four hospitalizations total. Notably, three hospitalizations occurred in the placebo arm and one in the low-dose Bucillamine group (300mg/day), while no hospitalizations occurred in the high-dose Bucillamine group (600mg/day).
The study also demonstrated that for patients with oxygen saturation below 96% at baseline, Bucillamine showed a 29.1% improvement over placebo in time to normal oxygen saturation.
Scientific Rationale for Thiol-Based Approach
Research published in a study titled "Thiol-based drugs decrease binding of SARS-CoV-2 spike protein to its receptor and inhibit SARS-CoV-2 cell entry" provides mechanistic support for Bucillamine's potential efficacy. The study showed that thiol-based drugs like Bucillamine decrease SARS-CoV-2 spike protein binding to its receptor, reduce viral entry efficiency, and inhibit live virus infection.
Multiple Therapeutic Applications Under Development
Beyond long COVID, Revive and AMS are preparing plans for potential commercial scale-up to support public health medical emergencies, including pandemic influenza and emerging infectious diseases. The enhanced formulation may also support Revive's ongoing research project with Defence R&D Canada - Suffield to evaluate Bucillamine as a potential treatment for nerve agent exposure.
As a potent antioxidant and anti-inflammatory agent, Bucillamine may prove beneficial for orphan indications in rare inflammatory disorders such as ischemia-reperfusion injury related to organ transplantation. The FDA granted orphan drug designation for this indication in 2022.
The collaboration positions Revive to leverage multiple regulatory incentives, including Emergency Use Authorization, Orphan Drug, Fast Track, and Breakthrough Therapy designations as the company advances Bucillamine through clinical development for various therapeutic applications.
