Moderna's announcement Monday that its experimental coronavirus vaccine spurred potentially meaningful immune responses in eight patients was good enough news to lift global markets and enable the Massachusetts-based biotech to raise more than $1 billion from investors.
But more is unknown than known about how well, if at all, the vaccine will prevent cases of COVID-19. Also unclear is whether the vaccine will be safe enough to use in the broad population, especially since treatments using Moderna's messenger RNA technology have never before received full regulatory approval.
Monday's news set expectations even higher, and any setback now could be damaging not just for Moderna, but also for hopes that the pandemic can be defeated in 2021.
"We're in the 'science by press release' age," Paul Offit, director of the vaccine education center at Children's Hospital of Philadelphia, said in an interview with BioPharma Dive. "I just wish there were more data before people step up to the microphone."
The main aim of the Phase 1 study the National Institutes of Health ran for Moderna's vaccine was to establish its safety before testing it on a larger groups of patients. For the most part, mRNA-1273, as it's called, met that goal. However, the information accompanying those safety results — eagerly awaited signs that the vaccine induces an immune response — were far less clear.
Without revealing specifics, Moderna said a total of 25 participants who received two shots of either a low or medium dose of mRNA-1273 had levels of binding antibodies — proteins recruited by the immune system to fight the virus — that reached or exceeded levels found in the blood of recovered COVID-19 patients.
Data on the more significant neutralizing antibodies, which stop viruses from entering cells, were available for four patients in each of those two dose groups. Moderna said antibody levels were at or above that seen in recovered COVID-19 patients, again, without providing detailed data.
William Petri, an epidemiology professor at the University of Virginia, said the results show that researchers have correctly identified a good target on the virus' surface to keep it from entering cells and reproducing itself. Vaccines for other viruses, like HIV, haven't even gotten that far.
"That's a huge advance because it has taken us 30 years to try to understand what is a protective antibody response for HIV," Petri said in an interview with BioPharma Dive. "With this infection, we know from the get-go that this is the immune response that we want to generate."
He added, however, that until the vaccine is tested against a placebo, it won't be clear whether that response is strong enough to prevent infection. Moderna is planning more advanced trials to begin in coming months, with a Phase 3 trial planned for July.
Adding to the uncertainty is Moderna's reluctance to reveal specific numbers on the antibody concentrations seen in the trial. The company said it was leaving that data to the NIH and clinical trial sites, which will want to publish more in a peer-reviewed journal.
In addition, Tal Zaks, Moderna's chief medical officer, cautioned that SARS-CoV-2 is such a new virus that researchers are still trying to determine, from the blood samples of recovered patients, what a meaningful immune response looks like. Specific numbers of antibodies initially observered could therefore be misleading, Zaks suggested.
"I don't think it'd be appropriate to just give a number out there because what's relevant is not the number; it's our confidence and context of what that number means," Zaks told analysts in a conference call Monday.
Moderna recognized this issue in its Securities and Exchange Commission filing on its share sale, stating blood samples "have been taken from a small number of people and may not be representative of the antibody levels in a broader population of people who have recovered from COVID-19."
The vaccine's safety profile is still uncertain, despite the early and generally positive results. This is especially noteworthy because Moderna's technology, which tells cells to produce the coronavirus' characteristic spike protein, triggering an immune attack, has never been used in a drug that has received Food and Drug Administration approval. The same approach is being used by another leading coronavirus vaccine candidate from BioNTech and Pfizer.
Patients receiving the 25 and 100 microgram doses experienced mostly mild injection site reactions, but a third dose group, receiving two shots of 250 micrograms, produced severe "systemic symptoms," which Moderna described as fever-like.
The company is not planning on using that high dose in the next set of trials, although further testing could reveal cases of fever in patients who get the lower doses. Nonetheless, both Offit and Petri noted that fever is a side effect of the shingles vaccine Shingrix, and the FDA viewed it as safe enough even though shingles does not have the death rate of COVID-19.
Nonetheless, far more patients need to be tested, and followed over a longer period of time, to truly know if the vaccine is safe. "You don't know about uncommon side effects," Offit said, nor whether it can defeat the coronavirus.
To demonstrate that the vaccine actually will work to defeat the coronavirus, Offit offered some numbers. "I'd like to see roughly 20,000 vaccinated, 10,000 getting placebo. A few hundred placebo patients get sick, very few in the vaccinated group get sick," he said. "That's what I want to see."