Revive Therapeutics To Schedule DSMB Meeting In Lieu Of FDA Decision
Revive Therapeutics Ltd. (CNSX: RVV) (OTCMKTS: RVVTF) obtained a material ruling from the U.S. Food & Drug Administration (FDA) pertaining to its current Phase 3 clinical trial to evaluate the safety and efficacy of Bucillamine to treat COVID-19. While dour sentiment was reflected on the public exchanges, the ruling does not explicitly change the trajectory of the trial, from an analytical perspective.
On Wednesday, Revive Therapeutics announced that pursuant to its intention to pursue new primary symptoms endpoints, the FDA determined that Revive’s proposed amended endpoint protocol, while still under review, does not support the time to resolution via the polymerase chain reaction (PCR) test. The PCR data was envisioned to be an important supportive biomarker in measuring time to resolution of symptoms and secondary endpoints in patients with mild-moderate COVID-19 receiving Bucillamine therapy compared with those receiving placebo.
However, the FDA’s determination does not mean that Revive’s trial is over, or even necessarily diminished—at least from an analytical perspective. The company still intends to pursue a Data Safety Monitoring Board (DSMB) meeting to review statistical trial data and advance the study:
As a result, to potentially obtain FDA agreement and strengthen the relevance of the revised endpoint, which relied upon the Study’s Pre-Dose selection data, the Data Safety Monitoring Board (“DSMB”) will review the completed Post-Dose selection data of approximately 500 subjects… Regardless of the outcome, the Company would proceed to seek a meeting with the FDA to agree on a proposed plan for potential regulatory approval…Revive Therapeutics Provides Update on Phase 3 Clinical Trial for Bucillamine in COVID-19, September 28, 2022
Pursuant to a prospective DSMB meeting, the committee shall offer one of several possible courses of action:
• Make a recommendation on continuing the study by enrolling additional patients
• Advise on halting the study early due to positive efficacy showing statistical significance
• Recommend halting the trial due to lack of safety and/or efficacy
So while Wednesday’s FDA ruling undoubtedly takes Revive Therapeutics’ COVID-19 trial down a more winding path, the DSMB will remain the ultimate arbiter of trial outcome. This includes the possibility of providing valuable feedback (i.e. trend analysis pertaining to the resolution of symptoms) to Revive as it inevitably re-engages endpoint swap discussions with the FDA.
Revive Remains In Discussion With The FDA
Although today’s news was not a best-case scenario for Revive, it was far from an outright rejection that could have diminished the trial’s prospects significantly. The FDA simply set preliminary parameters on which types of endpoints, and the basis thereof, that it is willing to consider before moving forward—but is keeping the discussion going. The press release explicitly states that the FDA is amenable to meeting further “to discuss the appropriate endpoints and justification of the relevance of the revised primary endpoint.”
Therefore, the FDA has not slammed the door on potential endpoint change submission. It is simply seeking the appropriate justification and relevant data points in which to do so.
According to Revive CEO Michael Frank, whom TDR spoke with earlier today, DSMB input in the next phase will be important in determining next steps towards endpoint protocol resolution. “We look forward to presenting additional post-dose selection data covering approximately 500 trial patients to the DSMB,” said Mr. Frank. “From there, we anticipate receiving valuable feedback that may be used to further negotiations with the FDA regarding revised endpoint submission. This is our next point of focus in the coming weeks.”
While today’s decision may be interpreted as a setback for Revive, it’s essential to note that the FDA’s ruling was conceptual, not statistical. The FDA does not believe PCR data should be the primary basis of new symptoms endpoints sought by Revive, so another path must be chosen. However, in no way does the FDA’s ruling reflect on the robustness, or lack thereof, of Revive’s patient data. It is predominantly a procedural obstacle in which the FDA is amenable to revisit once new protocols are developed.
TDR will have additional coverage as warranted.