When COVID-19 first presented itself in December 2019, almost two years ago, drugmakers (and others) were caught blindsided. The big three that have emerged since then—Pfizer/BioNTech, Moderna and Johnson & Johnson—are determined to make sure history doesn’t repeat itself so soon.
As soon as—and even before—news of the omicron (B.1.1.529) variant spread over Thanksgiving weekend, the pharmaceutical companies each had strategies they could start implementing to handle possibly the most dangerous strain of SARS-CoV-2 we have seen yet. The omicron variant, which is reported to differ significantly from other strains like beta and delta, has 32 mutations in the spike protein—the target for existing vaccines.
Pfizer/BioNTech and Moderna both said they expect to know if their current vaccine dosages are effective against the omicron variant in about 2 weeks.
"Pfizer and BioNTech have taken actions months ago to be able to adapt the mRNA vaccine within 6 weeks and ship initial batches within 100 days in the event of an escape variant," a BioNTech spokesperson said. "To that end, the companies have begun clinical trials with variant-specific vaccines (alpha and delta) to collect safety and tolerability data that can be provided to regulators.”
Moderna and Pfizer/BioNTech have a leg up on Johnson & Johnson as their COVID-19 vaccines are based on mRNA technology, shortening the time needed to create a booster.
“From the beginning, we have said that as we seek to defeat the pandemic, it is imperative that we are proactive as the virus evolves. The mutations in the omicron variant are concerning and for several days, we have been moving as fast as possible to execute our strategy to address this variant,” said Stéphane Bancel, Chief Executive Officer of Moderna.
Moderna’s strategy is three-fold: 1) a higher dose booster of mRNA-1273 (the original); 2) multi-valent booster candidates designed to anticipate mutations; and 3) an omicron-specific booster candidate.
The pharmaceutical company has already begun testing the safety and immunogenicity of a 100 µg booster—as opposed to the current 50 µg booster of mRNA-1273. Dosing as been completed in 306 participants, and preliminary results indicate the highest neutralizing titers against prior SARS-CoV-2 strains. Now, Moderna is working to rapidly test sera from the high-dose booster participants to determine if the 100 µg dose provides neutralizing protection against omicron, specifically.
Moderna is also studying two multi-valent booster candidates—mRNA-1273.211 and mRNA-1273.213—that include several mutations present in the omicron variant, as well as the beta and delta strains. The company has completed dosing in a safety and immunogenicity study for both booster candidates at the 100 µg dose level. mRNA-1273.211 has also been tested at 50 µg, while Moderna plans to explore that dose level for 1273.213 in approximately 584 participants ASAP.
Lastly, Moderna said it will seek to rapidly advance mRNA-1273.529, an omicron-specific booster candidate the company says it can advance to clinical testing in 60 to 90 days.
Like Moderna, Johnson & Johnson, who’s initial COVID-19 vaccine is based on viral vector technology, said it is already testing blood serum from participants in completed and ongoing booster studies to look for neutralizing activity against the omicron variant. In addition, the pharmaceutical giant said it is pursuing an omicron-specific variant vaccine and will progress it as needed.
“It’s standard procedure to begin developing an updated vaccine in parallel with running tests of how the new strain reacts with the existing shot in order not to waste any time,” a BioNTech representative told Bloomberg. “Lab tests will deliver more information on whether or not adaption of the vaccine will be necessary.”
Pfizer has additional reason to be optimistic about controlling the omicron variant as the company is currently seeking Emergency Use Authorization for investigational oral pill PAXLOVID (PF-07321332) for the treatment of mild to moderate COVID-19 in patients at increased risk of hospitalization or death. The pharma giant submitted data to the FDA for EUA approval on Nov. 16.
In an interview with CNBC, Pfizer CEO Albert Bourla expressed confidence in PAXLOVID, regardless of mutation or strain.
"I'm very, very confident that this drug works for all known mutations, including the omicron one," Bourla said. "But we are working on other drugs for the eventual case that maybe a resistance is developed."
In a clinical trial for adults aged 18 and older with high-risk COVID-19, patients who received PAXLOVID showed an 89% reduction in risk of hospitalization or death, compared with those who received a placebo within three days of symptom onset, with no deaths in the treatment group. Similar results were seen when treatment was administered within five days of symptom onset.
Bourla said Pfizer designed the oral treatment with the ever-evolving mutations in mind, especially ones that affect the spike protein—like omicron. PAXLOVID works by blocking the activity of the SARS-CoV-2-3CL protease, an enzyme the coronavirus needs to replicate. It is administered with a low dose of the HIV drug ritonavir, which slows the metabolism and allows PAXLOVID to remain active in the body for longer periods of time at higher concentrations.
If authorized or approved, PAXLOVID will be administered at a dose of 300 mg (two 150 mg tablets) of PF-07321332 with one 100 mg tablet of ritonavir, given twice-daily for five days.