Moderna bolsters global hopes in Covid-19 vaccines, but big obstacles remain
Where does the world go from here?
Eleven months after word first broke out, two companies now say they have developed an effective Covid-19 vaccine, a key triumph in the fight against the worst pandemic in a century and the first major round of evidence for a previously untested genetic technology whose rapid response potential long captured the imaginations of researchers in the US and Europe.
Experts cautioned for months that mRNA was unproven and the first vaccines may only be 60% or 70% effective, if they worked at all. Now both frontrunners say they prevent disease more than 90% of the time.
“All the boxes have now been checked,” NIAID chief Tony Fauci told reporters Monday morning. “The platform clearly works, it worked here with Moderna, it worked with Pfizer.”
Although both rounds of results came by press release, Moderna’s announcement clarified key questions. They gave the first snapshots for safety data and the first demographic breakdown of who came down with Covid-19 in the trial.
They also showed that it likely helped prevent hospitalization and death, with 11 cases of severe disease occurring in the placebo group and zero occurring in the vaccine group, answering a key question FDA advisors raised during a recent committee hearing.
Paul Offit“Arguably it’s 100% effective at preventing severe disease based on those data,” Paul Offit, director of the Vaccine Education Center and a member of the FDA vaccine advisory committee, told Endpoints News. “But it’s not shocking. It’s actually harder to prevent mild disease.”
And yet the US and the world still face the same question that has always loomed at the end of the first major trials: how to scale up a vaccine once it’s authorized, and how to get vaccine-skeptic corners of the country to take it once it’s available.
The six companies involved in Operation Warp Speed have all talked about making a huge number of doses for next year, and the government has invested in scaling up their technology. Still, biologics are tricky to produce, and Moderna and Pfizer say they will only be able to make enough to vaccinate 20 million Americans combined this year. At one point, US officials had talked about having 300 million doses available by January.
Jesse Goodman“I was struck by the relatively low number of doses,” former FDA chief scientist Jesse Goodman told Endpoints. “Scale-up of these technologies is something we’re all still learning about and we have to keep our fingers crossed that that all goes well.”
There’s a chance that the US government could look to exercise the Defense Production Act to ramp up manufacturing, Warp Speed vaccine lead Matthew Hepburn told reporters Monday, although he cautioned that they were “looking at all the tools available.”
Still, the data today showing Moderna can keep their vaccine at refrigerator temperatures were crucial, government officials and outside experts said, helping alleviate concerns about how well rural areas will be able to handle the -70 degree cold chain Pfizer’s vaccine required.
“This is really good news,” Norbert Pardi, who studies mRNA vaccines at the University of Pennsylvania, told Endpoints.
Norbert PardiModerna CEO Stéphane Bancel said in an interview with Endpoints Sunday that the biggest limiting step for the company’s manufacturing was raw material, as they have already built the capacity and hired the staff to ramp up to maximum production. They should be able to make between 500 million and 1 billion vaccines next year, he said.
No plans have yet been finalized for rolling out the vaccine, with US officials putting much of the burden on cash-strapped states. Despite those obstacles, Fauci reiterated Monday that he expects the vaccine will be able to be rolled out to the general population by April.
By that time, other vaccines will likely also have crossed the finish line, including a one-shot viral vector inoculation from J&J, a two-shot jab from AstraZeneca and protein-based vaccines from Sanofi and Novavax. They will all still have to prove themselves in late-stage trials, but the Moderna and Pfizer news has bolstered confidence, particularly in the viral vector vaccines.
The vectors operate on a similar genetic principle to the mRNA vaccines, delivering instructions for cells to produce the coronavirus spike protein.
“You can argue this validates the general approach,” Offit said. “They’re just different ways of getting the gene inside cells.”
Still, despite the early signs of success, mRNA still has its skeptics. Maria Bottazzi, a vaccinologist at Baylor University who is developing a protein-based Covid-19 vaccine, said that the speed of the platform made sense for tackling more controlled outbreaks. But she argued that given the size of the current pandemic, more money should have gone toward accelerating protein-based vaccines.
Maria BottazziThese approaches are more scalable and early studies induced more neutralizing antibodies, she said, potentially conferring longer-term protection. She also questioned whether the side effect profile — fatigue in 9.7% of participants and muscle ache in 8.9% — could make some hesitant to take the vaccine.
“The adverse events and the range of the scoring — it’s not fabulous,” she said. “These have to be deployed in a large number of people, in high education and low education, and we have to make sure some people use it and we already know confidence is not very high.”
Pardi said the safety data was “acceptable,” but Offit said he needed to see the full analysis. He noted that the Phase I trial indicated higher rates of side effects, including fever. That would make it similar to the shingles vaccine from GlaxoSmithKline, Shingrix.
“Often people will say to people that get Shingrix, get it on Friday, so you don’t miss a day of work,” Offit said. “If there’s fever and enough side effects associated with fever that would cause one to miss a day of work, you have to make sure that if you’re vaccinating your ER staff, you don’t vaccinate them all the same day.”
Several questions around immunity and protection still remain, including whether or not the Pfizer or Moderna vaccine can prevent people from getting infected or reduce the amount of virus they shed. That would give officials key information on whether and when measures like social distancing can be eased, although experts cautioned that the vaccines are unlikely to fully stop infection and the studies are not well-designed to prove if one did.
The bigger question will be over durability, a question that only time can answer. When the FDA reviews the vaccines, most participants will only be two months past inoculation.
“I’m optimistic,” Pardi said. “But I always need to mention and I always need to emphasize long-term followup will be critical and long-term followup will determine the actual efficacy.”
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