Ph2 OPTICOV to evaluate PAXLOVID +/- VEKLURY in IC patients with COVID-19

Today, March 17th, the Ph2 OPTICOV trial was amended to evaluate PAXOVID (oral, protease inhibitor, 300mg PAXLOVID boosted with 100mg ritonavir, generic name nirmatrelvir) with and without VEKLURY in immunocompromised (IC) patients. The trial is expected to start in May 2023 and its estimated primary completion date is in January 2024.

Highlights from NCT05587894:

• Population: The study is enrolling IC patients diagnosed with asymptomatic or mild-to-moderate COVID-19, regardless of symptoms onset (please see trial inclusion criteria for a list of which types of IC patients can be enrolled).
• Dosing: PAXLOVID will be assessed in 5-day and 10-day regimens with and without VEKLURY. Those treated with VEKLURY will receive a 200mg “flash” (the description suggests remdesivir will only be administered as a loading dose).
• Endpoints:
  • Primary: Percentage of patients with SARS-CoV-2 viral load  by RT-PCR in NP swabs at Day 10 after treatment initiation
  • Secondary: Time to first negative SARS-CoV-2 RT-PCR until day 90; all-cause hospitalization and/or death at day 28; number of DDIs who led to dosage adjustment of other patient's drugs
• Trial sites: Only one site in Geneva, Switzerland is currently listed.
• Note - This study was originally designed to test PAXLOVID in combination with EVUSHELD (IV, IM, neutralizing antibody, 300mg tixagevimab + 300mg cilgavimab, experimental name AZD7442).

CI Assessment:

• This is the second randomized study, in addition to Pfizer’s Ph2 EPIC-IC, that is evaluating 5 and 10 regimens of PAXLOVID in IC patients, which could drive use of PAXLOVID over VEKLURY and/or GS-5245 in patient population.
• Per last week’s FDA Advisory Committee meeting, experts anticipate a 10-day regimen of PAXLOVID may be necessary to optimally treat IC patients and mitigate the potential development of treatment resistant variants in IC patients. However, longer treatment durations may further complicate HCPs’ benefit/risk assessments for using PAXLOVID to treat IC patients with DDI risks.
• Use of Veklury in IC patients without serious DDI risks could be negatively impacted in IC patients if the PAXLOVID monotherapy arm demonstrates comparable results to that of the PAXLOVID + VEKLURY arms. However, this study may also lead to increased combination use of these therapies if those arms demonstrate substantially better results. This study may also further characterize the challenges of managing PAXLOVID-associated DDI risks for IC patients with COVID-19, which could reinforce use of VEKLURY, and eventually GS-5245, in IC patients.