The outlook for Revive Therapeutics Ltd. (CNSX: RVV, OTCMKTS: RVVTF) Phase 3 clinical trial to evaluate the safety and efficacy of Bucillamine to treat COVID-19 got a little brighter on Thursday. The U.S Food and Drug Administration appears to be amenable to the company’s submitted request to change the trial’s primary endpoints to a ‘symptoms’ focus, as announced on May 16. Although the FDA did not officially grant primary endpoint change yet, Thursday’s news was enough to catalyze forward-looking investors into action, sending Revive shares higher in the U.S. by +21.06% on the best volume in six weeks.
Revive Therapeutics reported that pursuant to its submitted request to change the trial’s primary endpoints to a ‘symptoms’ focus, it has received “positive comments” from the FDA in regards to its request to amend new primary efficacy endpoints for the current trial. This includes the rate of sustained clinical resolution of symptoms of COVID-19, which addresses the shift in clinical outcome. The positive comments following Revive’s May 16 submission are a constructive sign that the FDA is an ally in the endpoint change process.
Furthermore—and perhaps unexpectedly—the FDA agreed that Revive Therapeutics may unblind the pre-dose-selection data for the first 210 patients of the study to further support the new primary endpoint. In essence, the FDA is giving Revive an opportunity to look directly at a portion of the data to make sure they want to proceed with the proposed endpoint change. Up to this point, the entire dataset of the 715 patients already tabulated in the trial have been blinded to the company.
Revive will submit a Data Access Plan to the FDA in early June 2022 with the aim to unblind the pre-dose selection data and submit the amended study protocol with the new primary efficacy endpoints to the FDA.
Under FDA Guidance for Clinical Trial Sponsors, knowledge of unblinded interim comparisons from a clinical trial is generally not necessary for those conducting or sponsoring it. Further, such knowledge can bias the outcome of the study by inappropriately influencing its continuing conduct or the plan of analyses. Unblinded interim data and results of comparative interim analyses, therefore, should generally not be accessible by anyone other than Data Monitoring Committee (DMC)—aka Data Safety Monitoring Board (DSMB) in the current trial—or the statisticians performing these analyses and presenting them to the DMC.
So for Revive Therapeutics qualified statisticians to be allowed to peek under the hood before proceeding with symptoms endpoint change may be inferred as a goodwill gesture by the FDA.
Furthermore, Revive Therapeutics confirmed that the DSMB is scheduled to meet thereafter to evaluate the interim clinical and safety data and may make a recommendation on the study. This could involve the recommendation to continue or halt the study due to positive efficacy based on the resolution of symptoms of COVID-19—assuming the primary endpoint change to symptoms is approved. The DSMB could also recommend that the FDA consider Bucillamine for potential Emergency Use Authorization for the treatment of COVID-19 symptoms, should the data support such a recommendation.
The DSMB has previously met on three separate occasions and supported the continuation of the study each time. To date, no serious adverse events or safety concerns have been reported.
TDR will have additional coverage as events warrant.