Veru announced agreement with FDA on a confirmatory Ph3 clinical trial for sabizabulin for the treatment of hospitalized adult patients with moderate-to-severe SARS-CoV-2 infection

On May 4 2023 Veru announced an agreement with the FDA on a confirmatory Ph3 clinical trial design for sabizabulin (oral, tubulin polymerization inhibitor, 9mg once daily, alternative name VERU-111) for the treatment of hospitalized adult patients with moderate-to-severe SARS-CoV-2 infection at high-risk for acute respiratory distress syndrome (ARDS)

• Based on Veru’s April 27^th, 2023 meeting with the FDA, the FDA agreed to a randomized (1:1), multi-center, global, efficacy and safety study
• Study Arms: 9mg oral daily dose + standard of care (SoC) vs. placebo + SoC in 408 hospitalized adult patients 
• Indication: The patient population include all hospitalized moderate to severe COVID-19 patients defined as WHO-4 (passive, low flow oxygen), WHO-5 (forced, high flow oxygen), or WHO-6 (mechanical ventilation) without a requirement to have a comorbidity
• Endpoints:
  • Primary: All-cause mortality at Day 60
  • Secondary/Exploratory: Days in the hospital and ICU, Days on mechanical ventilation, proportion of patients alive without respiratory failure, presence of long COVID-19 symptoms at Day 180
• Timing: Enrolment to begin in H2-2023
• Data Readout and Regulatory Filing Plans:
  • Two interim efficacy analyses are planned, and if either planned interim analysis meets statistical significance criteria, the trial could be stopped
    • 1^st Interim Analysis: Expected to occur when ~50% of patients (204) have completed the Day 60 primary efficacy endpoint as recommended by FDA, expected in 2024
    • 2^nd Interim Analysis: Expected to occur when ~71% of patients (290) have completed the Day 60 primary efficacy endpoint
  • Veru could submit a new FDA EUA request and/or a rolling NDA submission (based on current FDA Fast Track Designation) if the primary endpoint demonstrates a statistically significant effect on all-cause mortality in favor of sabizabulin treatment

Assessment:

• The clinical trial design is in-line with expectations based on previous committee concerns noted during the FDA AdComm in Nov 2022; seemingly addressed with a larger enrolment number and a broader hospitalized population. With Veru generating sufficient capital and FDA alignment on trial design, sabizabulin continues to pose a potential competitive threat in the hospitalized treatment setting.
• based on this trial design, we could see combined use of sabizabulin and VEKLURY where the latter is SoC (e.g., the US); 
• Sabizabulin is still under regulatory review in certain ex-US countries based on its initial Ph3 study results (e.g., Europe, Canada). However, it remains unclear if these reviews will be delayed to await data from this new Ph3 study
• Given the currently lower hospitalization and mortality rates, it is questionable how feasible Veru’s 2024 interim analysis timelines are.
• Veru is likely to face similar enrolment challenges seen with other competitors, like Pfizer (PAXLOVID) and PharmaMar (plitidepsin), who conducted trials in hospitalized settings but ultimately terminated or withdrew their trials due to enrolment challenges