AstraZeneca, Oxford snare U.K. clearance for their COVID-19 vaccine

AstraZeneca's COVID-19 vaccine has had a bumpy ride to the finish line, navigating safety scares and confusion over which dosing regimen offers the greatest level of protection. While decisions in Europe and the U.S. are still a ways out, the British drugmaker managed to pull off an authorization in its native Britain in 2020's eleventh hour.

The U.K. Medicines and Healthcare products Regulatory Agency (MHRA) on Wednesday cleared AstraZeneca and the University of Oxford’s adenovirus shot for emergency use in people 18 years and older. The authorization allows AZ to release doses immediately, paving the way for vaccination starts early next year, the company said. AZ’s vaccine is the second to snag a green light in the U.K. after Pfizer and BioNTech’s shot.

The authorization recommends patients receive two 0.5-ml doses of AZ’s shot at an interval of between four and 12 weeks. It’s the same regimen that boasted 62% efficacy in interim analyses from late-stage trials in the U.K. and Brazil, well below the 90%-plus bar set by Pfizer and Moderna’s mRNA vaccines. AstraZeneca made waves earlier this year when it revealed a half-dose primer shot, given ahead of a full-dose booster, triggered a protection rate of 90%, more in line with the efficacy of its rivals.

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At the time, Executive Vice President Mene Pangalos, Ph.D., described the use of the half-dose regimen in AZ’s phase 3 as a mistake, though the apparent efficacy boost motivated the British drugmaker to dig deeper. Ruud Dobber, president of AZ’s U.S. business, told CNBC he expected regulators to focus on the half-dose regimen, hypothesizing the smaller initial dose may have worked by “priming the immune system with a relatively low dose or lower dose.”

The MHRA, for its part, didn’t find the data convincing enough to clear AZ’s half-dose regimen. Government advisers who worked on the authorization said the apparent benefit of the primer dose might have stemmed from a longer period between dosing in that particular subgroup, rather than the primer itself—though it did inspire the government's decision to recommend up to 12 weeks between shots, The Wall Street Journal reports.

“We felt the results were not borne out by the full analysis,” Munir Pirmohamed, a pharmacologist who chairs the U.K.’s Commission on Human Medicines (CHM) Expert Working Group—tasked with advising the CHM on potential COVID-19 vaccines—said in a media briefing Wednesday.

What's more, “effectiveness was high, up to 80%, when there was a three-month interval between first and second doses, which is the reason for our recommendation,” Pirmohamed added

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AZ has teamed up with Public Health England and National Health Service England to support the rollout in the U.K. and plans to supply millions of doses in the first quarter of 2021, part of an agreement to provide upward of 100 million doses total. Meanwhile, the company is continuing to work with global partners to build out manufacturing capacity for up to 3 billion doses globally in 2021 on a rolling basis, it says.

While AZ’s vaccine efficacy may appear slightly lackluster, the company’s shot could boast a distribution and storage edge over its competitors. Unlike Pfizer and Moderna’s mRNA shots, which must be kept at subzero temperatures, AstraZeneca’s vaccine can be stored, transported and handled at standard refrigerator temperatures of 2 degrees to 8 degrees Celsius (36 degrees to 46 degrees Fahrenheit) for at least six months, potentially easing rollout hurdles in regions lacking cold-chain support.

AZ’s vaccine may run cheaper than its rivals, too, and the company has pledged not to profit off its shot during the pandemic’s run. “This vaccine will be made available to some of the poorest regions of the world at a low cost, helping protect countless people from this awful disease,” Matt Hancock, U.K. secretary of state for health and social care, said in a release.

Meanwhile, AstraZeneca is plowing ahead on a U.S. phase 3, which it will need to wrap before it can file for approval in the country. In the meantime, the drugmaker is also pursuing an emergency use listing from the World Health Organization—a bid to speed up vaccine access in low- and middle-income countries.

Elsewhere, the Serum Institute of India—shoring up manufacturing and running clinical trials on AZ’s vaccine in India—applied in early December for emergency use authorization of the shot, dubbed Covishield in-country.

With three Western vaccines now cleared in various parts of the world, Johnson & Johnson and Novavax’s prophylactic hopefuls are the next likely candidates for an emergency nod. 

Novavax late this month kicked off a phase 3 study of its recombinant nanoparticle, adjuvanted vaccine in Mexico and the U.S. The study joins a slate of ongoing trials, including a phase 2b assessing safety and efficacy in South Africa, a pivotal phase 3 in the U.K. and an ongoing phase 1/2 in the U.S. and Australia. Data from those trials could emerge early in 2021’s first quarter, though it will depend on transmission rates in regions where the trials are running, Novavax said.