Impacts of AstraZeneca's COVID-19 Vaccine Trial Pause

Sep 10

The Impacts of AstraZeneca's COVID-19 Vaccine Trial Pause: The Good and the Bad

Updated Sep 13: Trial Resumed After the Pause

In the wake AstraZeneca’s pause of its late-stage COVID-19 vaccine trial due to a serious safety issue, we are all pondering what it could mean. While in the middle of enrolling tens of thousands of human participants, AstraZeneca voluntarily halts its global trial after a patient in U.K. experienced an adverse event—this was first reported by Stat on Tuesday. The New York Times reported that this patient was diagnosed with transverse myelitis, or inflammation of the spinal cord that can be triggered by infections.

AstraZeneca’s vaccine uses a chimpanzee adenovirus as a vehicle that has been modified to carry a tiny portion of the coronavirus genes and deliver them into human cells. The adenovirus is generally harmless because they are modified to be crippled and inactivated such that they do not multiply in humans like the real virus. The coronavirus components of the vaccine are intended to generate a protective immune response that would be retriggered in the event the actual coronavirus infects a vaccinated individual.

While this sudden news makes the vaccine seem like the main culprit, these trial pauses are rather “routine” mandates that allow the drug makers to properly conduct a safety review. This happens whenever there is a potentially unexplained illness in a clinical trial study. Even before this adverse issue was reported, there were lots of anxieties, in general, involving the safety of any of the COVID-19 vaccines in the development pipeline. Moreover, the push for an accelerated path of development incited added concerns to what was already there. Yes, safety should be assessed very carefully, and it should be evaluated in a large number of populations to achieve statistical confidence. To that end, the upside of this AstraZeneca trial hiccup is, we know that the company is committed to the safety evaluation and the highest standards of protocol to maintain the integrity of their clinical study. Safety is one of the main reasons why rigor is baked into a clinical trial design before a drug is approved for broader use. Not only that, in a late stage/phase 3 study, the investigators evaluate thousands of people to ensure safety and efficacy. AstraZeneca’s vaccine is currently in Phase 2/3 trials in England and India, and in Phase 3 trials in Brazil, South Africa, and the U.S. The company had plans to test this vaccine in 30,000 people in more than 60 sites in the U.S.

In large trials like this, it is not uncommon for the participants to become sick by chance. This sickness is reported as an adverse event. These adverse events are independently reviewed by a data safety monitoring board. After a thorough review, the data safety monitoring board determines whether the sickness is due to the drug, in this case, the vaccine, or due to an unrelated cause.

AstraZeneca is working to expedite this review to minimize the delay of trial completion. Although it is unclear as to how long the hold will last. If the event is determined to not be transverse myelitis or not related to the vaccine, some analysts think that the trial could proceed after a delay of weeks to months. It could take months for AstraZeneca to prove the problem wasn't associated with their vaccine. On the flip side, this trial would be “terminated” if indeed transverse myelitis is linked to the vaccine. Similarly, another serious adverse event could permanently halt the program altogether.

However, the Financial Times reported that the trial could resume next week, according to individuals familiar with the patient’s case--meaning that the serious adverse reaction is not due to the vaccine and that the company may have this issue under control.

What does all this mean for other lead COVID-19 vaccines? Well, there is still fierce competition in the overall COVID-19 vaccine landscape. Moderna now could be second in position to arrive in the market after Pfizer.

As a result of AstraZeneca’s safety issue, analysts think that other vaccine makers using adenovirus platforms, such as Johnson & Johnson and CanSino, could face slight delays as they may update their patient consent forms and patient brochures for trial enrollment.

Analysts also believe that companies using other vaccine platforms may not be impacted as much, however one can expect more scrutiny for vaccines using novel platforms, such as Pfizer’s and Moderna’s mRNA vaccines. Companies such as GlaxoSmithKline, Sanofi, and Novavax using traditional technologies or protein subunit vaccines are in the best place. Protein subunit vaccines use a tiny fragment of the virus to trigger an immune response to achieve immunity rather than introducing the whole virus (though crippled, inactivated, and non-infectious) to the body's immune system.

Updates from Sep 13

Oxford and AstraZeneca Resume COVID-19 Vaccine Trial After Halting It for a Safety Concern

AstraZeneca announced on Saturday that its coronavirus vaccine studies have resumed in the U.K., although not in the United States just yet. Their trials had been put on hold after a U.K. participant developed a neurological illness.

This particular vaccine was developed by the University of Oxford in partnership with AstraZeneca. The goal of the phase 3 (large) studies is to see whether the vaccine is capable of preventing COVID-19 and whether it is safe in thousands of people. It is common that the serious adverse reactions may not show up in the initial smaller/pilot studies; however, if there are any rare complications of a vaccine, it may not turn up until it has been administered to thousands, or tens of thousands of people—hence the need for a large trial investigation.

The Oxford and AstraZeneca trial has restarted in U.K. based on the conclusions derived from an independent review process as well as recommendations from both the independent safety review committee and the U.K. regulator, the MHRA. Although Oxford/AstraZeneca would not disclose information about the patient's illness due to participant confidentiality, they reassured that they are committed to ensuring the safety of their trial participants, the highest standards of trial conduct, and the monitoring of safety closely.

Sources: Stat, The New York Times, U.S. News, Fierce Pharma, and NPR

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