Actions speak louder than words, and a burst of well-meaning promises from biopharma to fight the coronavirus outbreak originating in China may have finally converted into action- although government agencies are still signalling for expectation management in the face of record-setting drug development speed.
Moderna announced that it has delivered its first RNA candidate to the National Institute of Allergy and Infectious Diseases (NIAID) for the prevention of the novel coronavirus. The mRNA vaccine, mRNA-1273, was produced just 42 days after selection of a target sequence, highlighting the utility of RNA as a means to produce both highly customisable and rapidly scalable drug candidates.
The company also took the opportunity to talk up its Norwood, Massachusetts manufacturing site as a means of enabling its rapid production time. It opened the facility in 2018, touting the new addition as a means to provide the "necessary scale and flexibility to support the development of high-quality mRNA medicines."
In the same breath, NIAID- partnered with Gilead Sciences- started a US trial of antiviral candidate remdesivir, on top of two trials previously disclosed in China. Thus far, data have only been released from a single patient, who experienced clinical improvement the day after treatment that enabled the discontinuation of oxygen therapy.
Separately, Gilead's work got a big endorsement from the World Health Organisation (WHO) this week, with an agency representative saying at a press conference that remdesivir is the only drug that "we think may have real efficacy." The company is conducting two trials of the antiviral in China- one in patients with mild or moderate COVID-19 respiratory disease, and one in patients with severe COVID-19 respiratory disease- and anticipates results in April.
The bigger picture
Much of the earlier biopharma activity around coronavirus treatment had been viewed as an attempt to bolster enthusiasm for stock offerings, as companies with little potential to make a near-term impact made broad statements about their antiviral offerings.
But outside of that opportunist sect, the outbreak has driven some truly impressive and rapid activity within biomedicine. Since its emergence in December, the SARS-CoV-2 virus, which causes COVID-19, has already stimulated significant research investments with the goal of treating, preventing, or abating the spread of the virus- including the rapid generation of a complete crystal structure and genomic sequence for SARS-CoV-2.
While companies like Gilead and Johnson & Johnson can scour through their small molecule libraries for antivirals with activity against related pathogens, much of the remainder of drug development in the space has centred on the virus' so-call spike protein- enabled by the rapid production of structural data from the virus. The protein is part of a complex that enables membrane fusion to host cells and subsequent infection, and has been the focus of new medicines for both prevention and treatment of COVID-19.
Moderna's vaccine candidate encodes an antigen modelled after the spike protein that is hoped to stimulate immunity; similarly, work from Regeneron Pharmaceuticals, Vir Biotechnology, and Sanofi to generate novel antibodies are all targeting the spike protein.
But speed is of the essence with the new therapeutics, and candidates to treat infection will face a shorter path to proven efficacy than a preventative vaccine. That certainly gives an advantage to re-purposed candidates like remdesivir, Tamiflu (oseltamivir), or darunavir, which can come with a package of safety data derived from prior patient exposure in Ebola, SARS, MERS, or HIV.
Speaking at a press briefing on February 25, NIAID director Anthony Fauci said that determining efficacy of a vaccine approach like Moderna's- "even at rocket speed"- would likely take about a year and a half, with three to four months dedicated to the Phase I study. He noted that clinical trials of remdesivir, on the other hand, could produce "an answer within a reasonable period of time."
However, any candidates that emerge successfully this spring from the growing group of Phase I studies will immediately hit an inflection point on whether to continue into Phase II development- one that will likely be decided by the severity of the pandemic at that time point, and the availability of continued funding from entities like NIAID.
While the rapid mobilisation of biopharma's energy against the outbreak has been an impressive feat, it's still not clear what, if any, positive impact the efforts might have on biopharma's bottom line. At Gilead in particular, the company has advertised its readiness to make substantial investments in manufacturing; however, analysts at Morgan Stanley highlight that the best sustainable gains for Gilead will come from a bolstered reputation, rather than drug sales.
Events could still conspire against the company on this front. The Chinese firm BrightGene has already claimed it has the ability to manufacture remdesivir- setting up a potential intellectual property dispute in a high-need region that isn't known for the integrity of its patent protection. Gilead management has already expressed its disinterest in getting entangled in a patent dispute for remdesivir- but permitting local product of an effective treatment mid-outbreak may not score the company any humanitarian points.
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