Covid-19 roundup: Gilead touts preclinical promise for oral remdesivir; Roche prepares for virus to become endemic
With remdesivir still standing as the only antiviral approved to treat Covid-19, Gilead has been exploring new ways to expand its use. Now its researchers, in collaboration with a team from the University of Carolina in Chapel Hill, have come up with preclinical results backing up an oral candidate.
And they have their sights set beyond Covid-19.
GS-621763, a prodrug of the parental nucleoside of remdesivir, appeared promising in both in vitro experiments in cell cultures and in vivo experiments involving mice. Notably, the scientists also compared GS-621763 against Merck’s molnupiravir, another oral nucleoside analog antiviral currently being tested in humans, and found both drugs to be “similarly efficacious.”
They started the paper, posted on bioRxiv, by noting that lagging vaccination rates, coupled with waning immunity and breakthrough infections by SARS-CoV-2 variants, highlight the need for second-generation treatments — but therapeutic options are limited. The ones that are available, such as remdesivir and the monoclonal antibodies, largely have to be infused intravenously, hindering widespread use, not to mention that some antibodies are showing signs of diminished efficacy against variants.
By targeting a highly conserved RNA-dependent RNA polymerase, GS-621763 is touted as an alternative candidate that can fight through all those mutations. Across studies, it showed “significant antiviral activity in lung cell lines and two different human primary lung cell culture systems” and triggered “dose-dependent antiviral activity in mice infected with SARS-CoV-2” with regards to viral load, lung pathology and pulmonary function, they reported in a preprint.
Gilead has also proposed the option of intranasal delivery, with trials for an inhaled formulation of remdesivir underway.
“Next-generation oral coronavirus (CoV) antivirals, if widely disseminated and given early in infection, could curtail the duration of disease, reduce long-term sequelae of COVID-19, minimize household transmissions, and lessen hospitalizations, thus having a broad impact on public health,” they wrote.
The goal, though, is not just to fight Covid-19, but any other coronavirus that emerges in the years to come.
The data provided herein supports the future evaluation of orally bioavailable prodrugs of GS-441524 in humans with COVID-19. If safe and effective, this class of RdRp inhibitors could become part of the arsenal of existing oral antivirals that are desperately needed to address a global unmet need for the COVID-19 pandemic and CoV pandemics of the future.
Predicting 200M-500M cases each year, Roche vows to keep up Covid-19 R&D
Roche doesn’t see Covid-19 going away any time soon, if ever.
That’s why the pharma giant will keep working on treatments and diagnostics against the coronavirus, said Barry Clinch, global head of infectious disease clinical development, on a conference call with analysts, per Bloomberg.
On top of making Covid-19 diagnostics and helping Regeneron manufacture its antibody cocktail, Roche is also developing an antiviral to tackle the infection.
The way Roche sees it, the disease will most likely become seasonal and endemic, with 200 million to 500 million new infections each year — not just another common cold.
While the virus will “become easier to manage over time,” it will still call for management, Clinch was quoted as saying, representing a middle ground between the best-case scenario of it disappearing and a worst-case scenario of it becoming unpredictable due to constant mutations.
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