Since the new coronavirus was first identified in Wuhan, China, on Jan. 7, companies and academic groups around the world have been working at breakneck pace to develop new therapies for the virus, now called SARS-CoV-2. This week, two US biotech firms, Moderna and Gilead Sciences, positioned themselves as frontrunners.
The world’s first clinical trial of a vaccine for the novel coronavirus will soon begin in the US. On Feb. 25, Moderna announced that it has shipped its experimental vaccine to the National Institutes of Health (NIH), which will conduct the trial. The entire process—from vaccine design to manufacturing to shipment—took only 7 weeks.
Separately, NIH says it has begun a clinical trial testing the ability of Gilead’s experimental drug remdesivir to treat people with COVID-19—the official name for the disease caused by the new coronavirus.
The news comes at a crucial moment. On Feb. 27, officials reported over 82,500 confirmed cases of the virus and more than 2,800 deaths. The majority of cases, over 78,000, are in China. And although the rate of new infections seems to be slowing in China, new outbreaks in Iran, Italy, and South Korea have the world on high alert. Experts suggest that a pandemic could be imminent, and the US Centers for Disease Control and Prevention warned that US communities should brace themselves for “disruption to everyday life.”
Gilead was able to move quickly because it conceived remdesivir, a small molecule, as an antiviral to treat people infected with Ebola virus. This month, researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, tested remdesivir in monkeys and showed that it can prevent and stop infections of Middle East respiratory syndrome coronavirus, which is related to the new coronavirus. Now, NIH is testing remdesivir in a Phase II study of people infected with SARS-CoV-2 at the University of Nebraska Medical Center.
Gilead has already shared remdesivir with hospitals in China that are running two Phase III clinical trials; results are expected in April. On Feb. 26, Gilead announced that it will launch two additional Phase III clinical trials of its own that together involve 1,000 people in Asia and elsewhere in the world. During a coronavirus forum held by WuXi AppTec, Thomas Cihlar, Gilead’s vice president of virology, suggested a successful trial could provide enough data for approval of remdesivir.
Moderna, meanwhile, wants to show that it can make experimental vaccines for COVID-19 and other new diseases more quickly than other companies.
Vaccines are typically made from bits of viral protein, molecular mugshots that our immune systems study so they know how to mount an attack against the real virus. But those mugshots are made by growing the viral proteins in millions of chicken eggs or in giant vats of cells—laborious and time-consuming processes.
Moderna takes a different approach. The company’s vaccines are made from messenger RNA (mRNA) molecules, which are instructions for making proteins. So instead of struggling to identify and grow the right viral protein bits, Moderna simply needs to know the genetic sequence of the virus that encodes them. It then can chemically synthesize the mRNA that encodes instructions for the viral protein.
Like other firms, Moderna has homed in on part of the coronavirus called spike proteins, which the virus uses to latch onto and infect cells. Moderna is packaging mRNA instructions for the spike protein into lipid nanoparticles. When the nanoparticles are injected into a person’s muscle, their cells should start making the spike protein. In theory, that gives the body a chance to study the protein and prepare for an infection of the real coronavirus.
Moderna began developing its coronavirus vaccine with the NIH in January with the help of funding from the Coalition for Epidemic Preparedness Innovation (CEPI). NIAID will conduct a clinical trial of the vaccine at Kaiser Permanente Washington Health Research Institute in Seattle. The study is designed to test the safety of the vaccine in 45 healthy adults.
The trial could begin in March or April, and investigators should be able to tell if the vaccine is safe and immunogenic after three months. If the Phase I trial is successful, a larger trial of hundreds to thousands of people will be launched to see if the vaccine is effective, NIAID director Anthony Fauci said in a White House press conference. That trial would take an additional 6 to 8 months.
“So although this is the fastest we’ve ever gone from a sequence of a virus to a trial,” Fauci said, wide deployment of a vaccine will still take 12 to 18 months, at best.
Perhaps the biggest risk with Moderna’s approach is that little is known about how well mRNA vaccines work in humans compared to traditional vaccines. Moderna has tested six other mRNA vaccines in Phase I trials for infectious diseases including influenza, chikungunya, respiratory syncytial virus, and Zika, but they are all years away from approval.
Manufacturing could also pose a problem. Although mRNA vaccines can be made faster than egg- and cell-based vaccines, Moderna has not indicated whether it has the capacity to scale up production for the millions of doses that could eventually be needed in the US. The company did not respond to an interview request.
While Moderna is the first to start human studies, many other firms are also developing coronavirus vaccines. Sanofi and Janssen are developing ones that rely on cells to produce bits of viral protein. Human testing would begin by the end of the year, at the earliest. Both firms are collaborating with the US Biomedical Advanced Research and Development Authority.
Smaller but potentially speedier vaccines are in the works as well. Inovio Pharmaceuticals, which makes DNA rather than mRNA vaccines, plans to begin clinical trials in the US and China in early summer. Novavax hopes to begin testing the safety of its nanoparticle vaccine in humans in May or June.
Like Moderna, Curevac received funding from CEPI to develop an mRNA vaccine against the virus, although the firm hasn’t provided a timeline of when it will be ready to test.
Other companies that have invested in mRNA vaccines include Pfizer, which partnered with BioNTech, and Sanofi Pasteur, which partnered with Translate Bio. None of these 4 companies have announced plans to develop mRNA vaccines for the new coronavirus.