Pomotrelvir did not meet the primary endpoint measured by proportion of participants below the limit of detection for infectious SARS-CoV-2 on day 3 of treatment with pomotrelvir vs. placebo
Otherwise healthy, vaccinated adults without risk factors for progression to severe disease experienced rapid clearance of SARS-CoV-2 virus and evidence of rapid alleviation of targeted and key
COVID-19 symptoms independent of treatment arm
Based on these results, Pardes to suspend further clinical development of pomotrelvir and explore
a range of strategic alternatives
“We continue to believe in the need for new oral antivirals for COVID-19, and the importance of continued investment in next generation therapeutics that will be needed to help prevent the next pandemic. However, these unexpected results have forced us to make the difficult decision to suspend further development of pomotrelvir and pursue alternative strategic opportunities for the company,” said
Topline Phase 2 Results
Pomotrelvir did not achieve the primary endpoint as measured by proportion of participants below the limit of detection for infectious SARS-CoV-2 on day 3 by infectious virus assay (IVA) with 70% reaching undetectable levels in the pomotrelvir treated group versus 63% in the placebo group (p=0.57). Pomotrelvir did not demonstrate meaningful improvement over placebo in reduction from baseline of SARS-CoV-2 infectious virus titer by IVA or in the reduction from baseline or proportion achieving undetectable viral load (RNA) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) measured from mid-turbinate swabs.
Table 1. SARS-CoV-2 Infectious Virus Titer and Viral Load by Study Treatment and Visit through Day 5
Infectious Virus Titer (by IVA) [log10 TCID50/mL] | Viral Load (RNA by qRT-PCR) [log10 copies/mL] | ||||||||
Pomotrelvir | Placebo | Pomotrelvir | Placebo | ||||||
N† | 53 | 32 | 153 | 77 | |||||
Baseline | 2.0 | 2.1 | 5.3 | 5.1 | |||||
Day 2 | Mean change | -1.0 | -0.7 | -0.7 | -0.6 | ||||
p-value | 0.11 | 0.47 | |||||||
Proportion negative | 45 | % | 31 | % | 17 | % | 21 | % | |
p-value | 0.17 | 0.43 | |||||||
Day 3 | Mean change | -1.4 | -1.3 | -1.5 | -1.0 | ||||
p-value | 0.40 | 0.05 | |||||||
Proportion negative | 70 | % | 63 | % | 27 | % | 26 | % | |
p-value | 0.57 | 0.81 | |||||||
Day 5 | Mean change | -1.6 | -1.8 | -2.6 | -2.6 | ||||
p-value | 0.78 | 0.79 | |||||||
Proportion negative | 96 | % | 97 | % | 46 | % | 59 | % | |
p-value | NE | 0.07 |
†N: Infectious virus titer assessments were conducted on the modified intent-to-treat virology (mITTV) analysis set, which is a subset of the modified intention to treat (mITT) analysis set that includes participants who had detectable infectious SARS-CoV-2 at Baseline/Day 1. Viral load assessments were conducted on the mITT analysis set, which includes all randomized participants with ≥ 2 symptoms consistent with COVID-19 ≤ 5 days prior to randomization and a positive SARS-CoV-2 test (qRT-PCR or RAT) ≤ 24 hours prior to randomization who received ≥ 1 dose of study drug.
Mean change from Baseline: p-value = difference between treatment groups by van Elteran test
Proportion negative: For IVA = below limit of detection (LOD, 0.375 log10 TCID50/mL); For viral load = undetectable RNA (1.24 log10 copies/mL); p-values = standardized risk difference between treatment groups by Mantel-Haenszel method (with adjustment for the following stratification factors: SARS-CoV-2 positive direct test diagnosis <= 3 days versus > 3 to 5 days from first onset of COVID-19 symptom(s))
NE = not evaluable
There were no deaths and no participants experienced progression to severe COVID-19. There were no drug-related adverse events, serious adverse events, or adverse events leading to discontinuation in either treatment arm. Pomotrelvir was well tolerated, with treatment-emergent, drug-related nausea occurring in 3.1% of participants, which represented the only adverse event occurring in greater than 2% of pomotrelvir-treated participants.
The median time to alleviation of the 14
Overall, baseline levels of SARS-CoV-2 infectious virus and viral load were lower, clearance of infectious virus was more rapid, and the speed of COVID-19 symptom improvement was faster than anticipated when the study was designed. These are important considerations when exploring the clinical benefit for potential SARS-CoV-2 therapeutics at this stage of the COVID-19 pandemic, with high levels of underlying population immunity due to vaccination plus ongoing community exposure to SARS-CoV-2 variants resulting in the likelihood of more modest viral burden and acute symptoms.
This study was conducted in otherwise healthy, vaccinated adults without risk factors for progression to severe disease with ≥ 2 symptoms consistent with COVID-19 for ≤ 5 days and with a positive SARS-CoV-2 test (qRT-PCR or RAT) within 24 hours of randomization. The majority (83%) of enrolled participants were randomized to treatment within 3 days of COVID-19 symptom onset. Participants received study drug treatment as soon as possible upon randomization and were instructed to take the full 1400 mg total daily dose of study drug on study day 1, followed by 700 mg twice-daily, approximately every 12 hours, administered with food, for a total of 5 days (10 doses).
The Company continues to analyze the results from this study and intends to submit these data to a scientific conference and/or peer-reviewed publication to contribute to the understanding of SARS-CoV-2 and the development of potential COVID-19 therapeutics.
Based on these results, the Company will suspend further clinical development of pomotrelvir and the Company’s Board of Directors has initiated a review of a range of strategic alternatives that may include, but are not limited to, an acquisition, merger, business combination, or other transaction. There can be no assurance that this review process will result in the Company pursuing a transaction or that any transaction, if pursued, will be completed on attractive terms or at all. The Company does not intend to comment further unless or until the Board of Directors has approved a definitive course of action, the review process is concluded, or it is determined that other disclosure is appropriate. As of
The Company’s unaudited financial statements for the three months ended
About Study PBI-0451-0002 (NCT 05543707)
The Phase 2 double-blind, randomized study enrolled 242 participants at 63 sites within
This Phase 2 clinical trial was powered to assess the primary endpoint of the proportion of participants below the limit of detection for infectious SARS-CoV-2 on Day 3 of treatment as measured by infectious virus assay from nasal swab samples. Secondary objectives assessed included the dynamics and time to negativity in SARS-CoV-2 viral load by both qRT-PCR and rapid antigen testing, safety and tolerability, and clinical efficacy through assessment of COVID-19 symptoms, hospitalizations and deaths through Day 28.
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Forward Looking Statements
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