AstraZeneca dumps late-phase, next-gen COVID-19 vaccine, calling time on a beta player in an omicron world

Events have overtaken AstraZeneca’s next-generation beta variant COVID-19 vaccine. After moving the prospect into phase 2/3 last year, AstraZeneca saw beta fall down the list of the most worrying variants, culminating in today’s decision to dump the AZD2816 vaccine candidate.

The removal (PDF) of AZD2816 from the pipeline follows the conclusion of work that persuaded AstraZeneca to stick with Vaxzevria, its first-generation vaccine, rather than push ahead with plans to seek authorization for its beta-specific sibling. AstraZeneca's decision is underpinned by AZD2816's lack of differentiation against the now-dominant omicron.

“Vaxzevria was exactly the same—there was no meaningful difference between immunogenicity of 2816 and Vaxzevria. It meant there was no need to switch from one to the other because obviously switching vaccines at this stage is not an easy thing, from a manufacturing perspective, capacity perspective. It would have to be really considerably better to make that switch,” Mene Pangalos, EVP biopharmaceuticals R&D at AstraZeneca, said.

When beta was identified in October 2020, it represented the most worrying COVID-19 variant yet from an immune escape perspective. The virus has 10 changes across the spike protein and was soon shown to render first-generation vaccines less effective, with the efficacy of Novavax’s vaccine falling from 89% in the U.K. to 49% in beta-dominated South Africa. 

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AstraZeneca responded by tweaking its Vaxzevria in light of the small genetic differences between beta and the original SARS-CoV-2. At one point, the development of a beta-specific vaccine looked like a prudent move. Beta established itself in South Africa and was making inroads into some European countries around the time that AstraZeneca began its AZD2816 trial. However, first delta and then omicron swept beta away around the world, significantly reducing the need for a vaccine specifically against the once-worrisome variant. 

AstraZeneca dosed the first subjects in the phase 2/3 clinical trial in June, marking the start of a study that ultimately enrolled more than 2,800 people to evaluate the effect of its beta vaccine and its original Vaxzevria product in multiple different contexts. Investigators gave AZD2816 to unvaccinated individuals and to people who had previously received either Vaxzevria or an mRNA vaccine against COVID-19.

The rise and fall of AZD2816 offers a cautionary tale for Moderna and Pfizer, which have recently moved omicron-specific vaccines into clinical development. While omicron is far more prevalent than beta ever was, the pace with which it displaced delta, and the fact it differs so much from that formerly dominant variant, shows any jab against a specific form of SARS-CoV-2 could be rendered obsolete before it gets to market.

AstraZeneca disclosed the termination of AZD2816 in a quarterly update that also saw it remove a clutch of earlier-stage programs from its pipeline. The Big Pharma disclosed the divestitures of cholesterol drug MEDI5884, which it recently offloaded to Regio Biosciences, and an antibody for preventing pneumonia caused by Staphylococcus aureus. Both assets were in phase 2. Another phase 2 project, solid tumor candidate AZD2811, got the chop, as did three phase 1 programs, including the push to develop inhaled JAK inhibitor AZD0449 for use in patients with asthma.