After weeks of small-cap biotechs touting their wares as possible treatments for the new coronavirus emerging from Wuhan, China, an established big-cap group has begun work here, and Gilead’s candidate remdesivir might be a more realistic prospect. Certainly this is what shareholders believe: Gilead’s stock was up 4% in early trade today.
So far, however, remdesivir has only entered formal clinical trials in Ebola virus patients, and questions remain about how fast it can be trialled and approved against 2019-nCoV. A randomised, controlled trial in coronavirus patients in Wuhan is being set up, and despite the need for effective therapies and the US FDA’s eagerness to approve new products, clean safety and at least a hint of efficacy will be crucial.
Remdesivir has already been given to a 2019-nCoV patient in the US on compassionate grounds. That patient recovered and had no side effects, though more than a single-case study will be needed.
Nuc it from orbit
So far clinical data on the project is limited, its only trials having been two NIAID-sponsored studies in Ebola virus patients. Of particular interest is the phase II/III Palm study. This tested four drugs from different developers, and essentially kyboshed remdesivir’s development for Ebola when an independent data-monitoring board concluded that two of the other drugs worked better than Gilead’s molecule, and recommended that the study be halted. At that point 681 patients had been treated, 155 of them with remdesivir.
Theoretically Gilead could still bolster the approval case for remdesivir in 2019-nCoV by using safety data from the NIAID Ebola trials – but this is not without blemish. There were four serious adverse events in Palm that were judged to be potentially related to the trial drugs, two of which occurred in a patient treated with remdesivir. The patient had hypotension that resulted in the halting of a loading dose of remdesivir, and that was followed rapidly by cardiac arrest.
It should be noted, however, that the researchers stated that the adverse events in Palm “could not readily be distinguished” from the underlying Ebola infection.
|NIAID-sponsored trials of remdesivir in Ebola virus|
|Phase II/III||Palm: 1,500-patient trial in the Democratic Republic of the Congo and the US|
|Phase II||38-patient trial in Guinea and Liberia|
|Source: EvaluatePharma, clinicaltrials.gov.|
Also getting in on the action is Glaxosmithkline, this time not directly but in collaboration with the Coalition for Epidemic Preparedness Innovations. Through CEPI’s auspices researchers from the University of Queensland, Australia, will gain access to Glaxo’s pandemic vaccine adjuvant platform to aid their efforts to develop a coronavirus vaccine.
CEPI is already working with smaller biotechs including Curevac, Inovio and Moderna, and it is possible that these groups too could sign partnerships under which they could use Glaxo’s adjuvant technology.
None of these vaccine projects has yet reached the clinic, though, leaving Gilead’s nuc the only potential coronavirus project with at least some limited clinical data. But much more evidence of efficacy is needed in this specific infection, and remdesivir’s safety is not a slam-dunk. The new trial in Wuhan will be conducted at top speed; regulators must be certain that it is robust before rushing to approve.