AstraZeneca has come under a lot of slack for its perceived poor communication and weaker results than its mRNA rivals, but the U.K. Big Pharma is still gunning in the COVID vaccine R&D game as its steps up to beat back new variants.
AZ said Monday morning that it has started testing its new COVID vaccine, known as AZD2816, as a tweaked version using the same platform as its authorized (though not in the U.S.) pandemic vaccine AZD1222, aka Covishield/Vaxzevria.
AZD2816 has been built using the same adenoviral vector platform as its existing vax, with minor genetic alterations to the spike protein based specifically on the so-called beta (B.1.351, South African) variant.
The beta variant vaccine contains 10 changes across the spike protein, many of which are also seen in other variants of concern and lead to effects such as, reduced ability of antibodies induced against the original virus to block cell entry (K417N, E484K, N501Y); increased infectivity compared to the original virus (D614G); and reduced sensitivity of neutralizing antibodies to the original virus (L452R).
“These modifications are only minor and in all other ways the two vaccines are the same,” AstraZeneca says.
It has today started giving the tweaked vax to patients in its new phase 2/3 trial, and it's set up to assess its safety and immunogenicity in both previously vaccinated and unvaccinated adults.
The trial will sign up around 2,250 participants across the U.K. (where the so-called delta or Indian variant is predominant) as well as South Africa, Brazil and Poland.
Under the trial, AZD2816 will be given to those who have previously been fully vaccinated with two doses of Vaxzevria or an mRNA vaccine at least three months after their last injection.
In non-vaccinated subjects, AZD2816 will be given as two doses, four or12 weeks apart, or given as a second dose following a first dose of Vaxzevria four weeks apart.
The company will, however, likely need to keep a very close eye on safety given the still rare but mounting safety issues from its vaccine causing potentially fatal clots in a small number of those taking it in the real world. Many countries in Europe have already decided against using the vaccine, or restricted its use in younger adults who appear more at risk of these clots.
Efficacy will also be closely watched: AZ’s vaccine is seen as a second-tier solution against the new mRNA vaccines used now predominantly in the U.K., U.S. and Israel, though it's cheaper and easier to move around the globe given that it is not as protective compared to its rivals.
Given how close the new vaccine is to the old, it is hard to see how easily issues over safety and efficacy will be overcome, and, in a relatively small trial, safety too may be difficult to full ascertain when compared to a larger rollout.
In the U.S., it already looks unlikely that AZ will be given the nod for its original vaccine, given the high success rate of Pfizer-BioNTech and Moderna’s mRNA vaccines, which have proved pretty solid against new variants, though they have not been free of safety woes given that both, and Pfizer's especially, have been linked to a rare heart condition known as myocarditis, notably in younger males taking the shot.
If its variant booster wins through in the trial, it remains to be seen just how well it will be taken up.
“It is important we continue to stay ahead of genetically distinct variants of the coronavirus. AZD2816 should help broaden individuals immune response against emerging variants of concern,” said Mene Pangalos, Ph.D., executive vice president of biopharmaceuticals R&D as AstraZeneca.
“Initiating the phase 2/3 trial for AZD2816 means we can be prepared should a variant vaccine be required in the future.”
Initial data from the trial is expected later this year and, once available, “will be submitted to regulators for assessment as a next-generation booster vaccine and through an expedited regulatory pathway,” the company said.