AstraZeneca's COVID-19 vaccine 70% effective, shares fall

AstraZeneca’s COVID-19 vaccine has achieved 70% efficacy in a late-phase analysis. The 70% figure is an average that masks variation in the performance of two dosing regimens, one of which was found to be 90% effective.

With the Pfizer-BioNTech and Moderna vaccines achieving efficacy of around 94%, the bar was set high for AstraZeneca’s AZD1222. Overall, the COVID-19 vaccine, which AstraZeneca is developing with the University of Oxford, fell well short of that bar. Yet, the details offer encouragement that the vaccine can be highly effective and more broadly adopted than the other candidates.

The 70% efficacy figure is the average result for two regimens given to 11,636 people. Most subjects, 8,895, received the same dose for their first and second jabs. A smaller cohort, 2,741 subjects, got a half dose for the first jab followed by a full booster shot.

Vaccine efficacy in the cohort of subjects who received two full doses was 62%. Efficacy in subjects who began with a half dose was 90%. Nobody who received the vaccine was hospitalized or had a severe case of COVID-19. The difference between the two regimens may reflect AstraZeneca’s use of a chimpanzee viral vector to deliver the payload of the vaccine.

“One potential explanation for this is that the body is mounting an anti-vector immune response to the second dose, which is lower if the first dose is reduced; such an immune reaction could reduce the efficacy of the vaccine,” Gillies O’Bryan-Tear, chair of policy and communications for the Faculty of Pharmaceutical Medicine, said in a statement.

The relatively small number of subjects enrolled in the half-dose cohort makes it hard to draw firm conclusions about the finding. Further use of the regimen should show whether 90% is an accurate reflection of the effectiveness of the half-dose approach. The disclosure sparked criticism.

"The company tried to embellish their results by highlighting a reported 90% efficacy in a relatively small sub-set of subjects in the study. They did not disclose the exact number of events in each study, or how they calculated the blended 70% efficacy for the full cohort. The suggestion by the inventors that the small sample given the lower priming dose was evidence of superior efficacy only brings discredit to the program. We regard the data disclosure as premature and insufficient," SVB Leerink analyst Geoffrey Porges wrote in a note to investors.

Differences between the designs of the clinical trials of different vaccines may have contributed to the seemingly lower efficacy of AstraZeneca’s candidate. Notably, AstraZeneca’s U.K. trial swabbed participants weekly, positioning it to detect asymptomatic cases. Pfizer and Moderna’s results are based on symptomatic cases.

Safety was a concern during the development of AZD1222, with an adverse event putting the R&D program on pause at one point. AstraZeneca is yet to share late-phase safety and tolerability data but said no serious safety events related to the vaccine have been confirmed. Some observors were critical of the level of disclosure.

"The company is likely to be roundly criticized today for their disclosure, since the safety disclosure simply state that “no serious safety events related to the vaccine have been confirmed” which is hardly reassuring. They did not disclose any information about any actual safety events," Porges wrote.

AstraZeneca is preparing regulatory filings based on the data, including emergency use listing from the World Health Organization. AZD1222, unlike Pfizer and Moderna’s mRNA vaccines, is kept at normal refrigerator temperatures, lessening a logistical difficulty and making it more suitable for use in countries without widespread deep-freeze capabilities.

The deals AstraZeneca has put in place in recent months position AZD1222 to be used widely across the world. AstraZeneca, working with partners, expects to make 3 billion doses next year and sell them on a nonprofit basis at around $3 a dose. Porges doubts if the U.S. will be among the destinations of the doses.

"We believe that this product will never be licensed in the U.S. This belief is based on the design of the company’s pivotal trials (which does not appear to match the FDA’s requirements for representation of minorities, severe cases, previously infected individuals and elderly and other increase risk populations), and based on the occurrence of severe safety events (why take the risk) that resulted in the extended clinical hold on enrollment into the trials in the U.S.," the analyst wrote.

Shares in the Big Pharma were off nearly 1.5% in London trading Monday morning, showing just how high the bar for a COVID-19 vaccine now is and how complex the picture for its efficacy remains.