First clinical data show biopharma the way against Covid-19

Clinical development in tackling the Covid-19 pandemic has moved at pace. The first biopharma projects recently entered trials, and already the first clinical data – albeit from academic centres – have emerged.

True, the results, concerning the flu antiviral Avigan, the anti-HIV combination Kaletra and the antimalarial Plaquenil, are highly equivocal, and come with a range of caveats. But they represent the first hints of how Covid-19 could be tackled, if only to dampen the severity of the disease, and serve as an important guide for industry.

Already it is evident that existing antivirals might form a first line of attack for people infected with Covid-19, even if their activity is limited to blunting the course of disease (A Covid-19 treatment plan slowly emerges, March 18, 2020). The first clinical data with Gilead’s remdesivir, due in May, are keenly awaited.

Interest has grown around Avigan, the Taisho/Fujifilm drug that is available for treating flu in Japan, since it was added to China’s emergency Covid-19 treatment programme. Yesterday Chinese authorities published the first evidence of Avigan’s efficacy against coronavirus.

On the face of it the data were positive, with Avigan-treated patients clearing the virus in four days, versus 11 days for those given lopinavir. However, subjects were not enrolled in a randomised fashion, some got additional background therapy, and none seem to have been severely ill – the very setting that a front-line treatment should target.

Intriguingly, China is claiming that no serious adverse events were seen; Avigan is known to carry numerous toxicities, and indeed its development outside Japan had largely been discontinued. Like Avigan remdesivir is an RNA polymerase inhibitor, so there could be a read-across to the Gilead trials.

Failure or success?

Also yesterday the first clinical data concerning Abbvie’s anti-HIV combo Kaletra in Covid-19 were published in the NEJM by academic teams at several Chinese centres. The authors were clear: the study failed, showing no benefit for Kaletra versus standard care in time to clinical improvement.

However, Evercore ISI’s Umer Raffat disagreed, pointing to subjects in whom treatment was initiated relatively quickly. In patients given Kaletra within 12 days of symptom onset, mortality was 15%, versus 27% for standard of care.

This subset comprised just 19 subjects. But it has set another benchmark for the remdesivir trials.

Finally, Professor Didier Raoult of the IHU Méditerranée Infection in Marseille reported data via a Youtube video on 24 Covid-19 subjects given the malaria drug Plaquenil. He claimed that after six days only 25% of the subjects tested positive for Covid-19, versus 90% in a separate group of untreated patients.

The caveats are that these are unpublished results from a trial without a formal control cohort. Choloroquine, the non-hydroxylated version of Plaquenil’s active ingredient, is separately in a 10,000-subject Covid-19 prevention study at the UK’s University of Oxford.

Trial initiation

Other studies listed in the past day include Massachusetts General’s Covid-19 prevention trial using inhaled nitric oxide; the idea had been mooted by Mallinckrodt a week ago.

The private company Pulmotect has started a prevention study using inhaled PUL-042, which appears to be a TLR 2/6/9 agonist. In January Pulmotect claimed to have seen positive preclinical signals.

And Roche moved to begin a phase III study of Actemra in 330 Covid-19 patients, cautioning that there was very little evidence backing IL-6 inhibition in coronavirus. Sanofi and Regeneron have separately begun a trial of the similarly acting Kevzara.