Preclinical potencies of clinical COVID-19 candidates
How clinical candidates for COVID-19 stack up preclinically against COVID-19, SARS-CoV and MERS-CoV
Among the several dozen agents in clinical testing for COVID-19, in vitro data against the new coronavirus have only been reported for four, and they support the WHO’s prioritization of remdesivir from Gilead Sciences Inc. (NASDAQ:GILD).
WHO's R&D Blueprint Clinical Trials expert group named remdesivir, a nucleotide analog, the most promising candidate for COVID-19 in a Jan. 29 draft report, and this week, Gilead announced plans to ramp up manufacturing of the compound, though it is not yet approved for any indication (see “Gilead Ramping Up Remdesivir Production” and “WHO Prioritizing Gilead’s Remdesivir”).
The WHO group chose the combination of lopinavir and ritonavir as a “suitable second option for rapid implementation in clinical trials.”
Data from lopinavir and ritonavir have not been reported against COVID-19, but their potency against two other coronaviruses -- severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) -- can be compared to remdesivir and other therapies (see Table: “In vitro EC50s of COVID-19 clinical candidates”).
Several groups have reported in vitro data again SARS-CoV and MERS-CoV that could hint at efficacy in COVID-19 patients.
As of Feb. 7, at least 31 trials of COVID-19 therapies were under way. One group of trials is testing approved antivirals in combination with IFNα or IFNβ; another handful of trials is evaluating chloroquine or chloroquine derivatives; and at least two trials are testing remdesivir (see "Clinical Trials for Coronavirus Have Begun").
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Table: In vitro EC50s of COVID-19 clinical candidates
Among the seven clinical COVID-19 interventions that have publicly available EC50 data for inhibition of COVID-19, SARS-CoV or MERS-CoV replication in cells, remdesivir from Gilead Sciences Inc. (NASDAQ:GILD) is the most potent. Lopinavir and ritonavir are being tested as a combination in the clinic; the table includes in vitro data from the compounds both as monotherapies and in combination.
With the exception of Avigan favipiravir from Fujifilm Holdings Corp. (Tokyo:4901) and remdesivir, all the candidates listed have been approved in the U.S. for other indications and are available as generics. Interferon potencies are given in international units (IU)/mL, and IFNα potencies comprise data for all isoforms. The remaining potencies are given in μM. Source: Scientific literature
IFNα - Interferon α
IFNβ - Interferon β