Explained: What pause in Johnson & Johnson Covid-19 vaccine trial means

 The Indian Express,

October 15, 2020

A COVID-19 vaccine developed by Johnson & Johnson subsidiary Janssen Pharmaceutica has come under the spotlight after late-stage human trials were paused over a potential safety concern. This vaccine uses the same approach as that of Oxford-AstraZeneca — whose trials were globally paused over similar concerns last month.

What do we know about the pause?

Late on Monday, trials for Janssen’s vaccine candidate, including phase 3 testing with 60,000 participants, were put on pause after a participant developed an “unexplained illness”. According to J&J, the illness is being reviewed by an independent Data Safety Monitoring Board as well as J&J’s internal clinical and safety physicians. The pause — decided by the company and not regulators — basically means the firm will temporarily halt recruitment and dosing of participants.

What is common between the two trials that were halted?

In the Oxford-AstraZeneca trials, a participant in the UK had developed a serious reaction. While AstraZeneca declined to disclose the nature of the illness, the patient had reportedly developed a neurological disorder called ‘transverse myelitis’ — an inflammation of a section or both sides of the spinal cord.

Other vaccines in large-scale, advanced human trials include mRNA vaccines from Moderna and Pfizer, as well as “inactivated” vaccines (which involve killing the SARS-CoV-2 virus for injection) from China’s Sinopharm. So far, none of these trials has been paused over potential serious adverse events (SAEs).

Janssen’s vaccine, like Oxford-AstraZeneca’s, uses a modified adenovirus — a common cold virus — to act like a Trojan horse that can deploy the SARS-CoV-2 virus’s “spike protein” to human cells. The Oxford vaccine uses a genetically engineered chimpanzee adenovirus; the Janssen one uses a variant of a human adenovirus known as Ad26.

Are we seeing a pattern, then?

In the context of the halted trials, the similarities between the Janssen and Oxford-AstraZeneca candidates may end with the vaccine platform. It is likely, some experts feel, that the potential safety concerns flagged with both vaccines are more a coincidence than a pattern. For one, there are several other adenovirus vaccines either in late-stage or post-marketing trials without similar incidents, according to them. These includes candidates developed by China’s CanSino Biological and Russia’s Gamaleya Research Institute. “With the preliminary information that we have, it would be too premature to say that the issues raised with the Janssen candidate have something to do with the (adenovirus) platform,” said vaccine expert Dr Davinder Gill.

“Primarily, there is also the question of whether this illness is vaccine-related. As it happened with the Oxford vaccine, once this incident is investigated a bit more, it may turn out that the reaction was not necessarily caused by the vaccine,” he said. “But I think we do have to keep an eye on these platforms.”

Gill said the adenovirus platform has been around for “at least” a decade, and a vaccine with a different variant of this virus was previously used in HIV trials. “Of course, in that case, it was tested on severely immunocompromised patients and, so it was a very different type of setting,” he said. “There is a concern, I think, with Covid-19 — for the first time, we are seeing these vectors being tested in very large patient cohorts. I think that, during these studies, we will learn more about how safe and how well tolerated these vectors are.”

Does this suggest the J&J vaccine isn’t safe?

The pause is not a matter of major concern at the moment, as there is no clarity on what caused the “unexplained” illness in the participant. It is not correct to assume this is a vaccine-related issue at this stage, and the pause is a precaution being taken as part of protocols. “Adverse events… even those that are serious, are an expected part of any clinical study, especially large studies,” stated J&J in a statement. “SAEs are not uncommon in clinical trials, and the number of SAEs can reasonably be expected to increase in trials involving large numbers of participants. Further, as many trials are placebo-controlled, it is not always immediately apparent whether a participant received a study treatment or a placebo.”

Gill pointed out that a very diverse population is recruited into phase 3 trials. “These people have all sorts of medical backgrounds and genetic predispositions, so it is not uncommon that something like this pops up sometimes during clinical trials,” said Gill. “Most of the time, it’s not related to the drug or the vaccine, but here, that needs to be investigated,” he said.

In any case, the real test of any Covid-19 vaccine, even one with a clean phase 3 record, will come when it is launched and used in the larger community. “That is where any potentially rare events that did not crop up during any of the trial phases will show up,” Gill said.

Do Indians need to worry?

The Janssen candidate has not yet been tested in India. Hyderabad-headquartered Biological E in August struck an agreement with Janssen to produce the vaccine and, while this is yet to start, the firm aims to make around 400-500 million doses a year. While Biological E has not commented, the outcome of J&J’s investigations may impact the future course of this agreement and determine whether this vaccine is tested on participants in India as well.

What happened to the Oxford-AstraZeneca trials after the pause?

Following reviews, the UK government allowed resumption of trials within the week. Shortly after, Serum Institute of India, which had been directed by the Indian drug regulator to pause its own testing of the Oxford -AstraZeneca candidate during the global pause, was given permission to resume its trials. It is currently conducting mid- to late-stage human trials of the vaccine. Trials for this vaccine have also resumed in South Africa, Brazil and Japan. However, the US is still looking into potential concerns with this adverse effect and, amid broadened investigations, trials there are yet to resume.

Reference: https://indianexpress.com/article/explained/what-pause-in-jj-covid-vaccine-trials-means-6727165/