Johnson & Johnson said it has temporarily paused further dosing of its adenoviral vector-based COVID-19 vaccine candidate, JNJ-78436735, due to an unexplained illness in a study participant. Trial enrollment is also on hold while the company awaits a recommendation on how to proceed from the study's data safety monitoring board. “It will be a few days at minimum for the right set of information to be gathered and evaluated,” said Mathai Mammen, global head of R&D for the company’s Janssen unit.
Neither the nature of the illness, of which J&J was informed on Oct. 11, nor any telling details about the affected patient have been disclosed so far, nor is it clear whether the affected patient received the vaccine candidate or a placebo. The company said its team is still "learning more about this participant’s illness, and it’s important to have all the facts before we share additional information."
"It's not at all unusual for unexpected illnesses to occur in large studies over their duration," said Mammen, adding that such events "may have something or nothing to do with the drug being investigated."
The recombinant non-replicating adenoviral vector vaccine, also sometimes called Ad26.COV2.S, has been developed in collaboration with the U.S. Biomedical Advanced Research and Development Authority and Beth Israel Deaconess Medical Center. It leverages J&J subsidiary Janssen's Advac technology platform. The same platform was used to develop and manufacture Janssen’s European Commission (EC)-approved Ebola vaccine and construct its Zika, respiratory syncytial virus and HIV vaccine candidates, the company said.
The trial interruption was, at least superficially, similar to the sudden stoppage of clinical activity around Astrazeneca plc's COVID-19 vaccine candidate, AZD-1222. Global trials of that candidate were put on hold during September following a reported case of transverse myelitis, or inflammation of the spinal cord, in one person who received the vaccine, but have since restarted in many countries, except the U.S. and Russia. Like J&J's candidate, AZD-1222 consists of a replication-deficient adenovirus vector encoding spike protein antigen from SARS-CoV-2. However, Astrazeneca is using a simian adenovirus while J&J is employing a human adenovirus.
No hold here
J&J was at pains to point out that a "study pause" is a "temporary" action taken by research sponsors, such as itself, rather than a regulatory hold place by the FDA.
But no matter the drivers of the move, it was clear that clinical activity in the company's studies is frozen for now.
Those trials include an ongoing phase I/IIa study designed to evaluate the safety and immunogenicity of two dose levels of the candidate as well as single and two-dose schedules. An interim analysis of the trial, announced Oct. 4, showed that a single dose induced a robust immune response and was generally well-tolerated, the company said.
The data were said to be "consistent with preclinical studies, published in the scientific journal Nature, which showed that a single dose of the vaccine successfully prevented subsequent infection and provided complete protection in the lungs of nonhuman primates," J&J said.
Based on the interim findings, the company decided to move ahead with a single dose containing 5x1010 virus particles in its pivotal phase III Ensemble trial, designed to enroll up to 60,000 volunteers across three continents, starting in the U.S.
It wasn't clear how many people have enrolled in the now-stopped placebo-controlled study, initiated in September. But the inclusion criteria at least paint a general picture of who they are: adults 18 or older, with what's hoped to be a "significant representation from those that are over age 60" with and without co-morbidities.
J&J has already made significant deals to supply the vaccine globally, announcing on Aug. 5 that the U.S. Department of Health and Human Services and Department of Defense (DoD) had agreed to support a large-scale manufacturing demonstration of the vaccine that would produce 100 million doses. Under the terms of the agreement, the federal government will own the resulting 100 million doses of vaccine. A BARDA contract/DoD contract was, at the time, expected to provide about $1 billion to support the manufacturing demonstration project, including support for the ability to deliver vaccine doses to government-designated locations across the country.
On Oct. 8, the EC also approved an advance purchase agreement, giving European Union Member States an option to secure up to 400 million doses of the vaccine. A similar supply deal was made with Canada.
During J&J's third-quarter earnings call, held Oct. 13, Chief Financial Officer Joe Wolk told investors that the company has been scaling up its manufacturing capacity, putting it on track to deliver more than 1 million doses of a COVID-19 vaccine per year. Furthermore, he said, the company has committed to provide the vaccine, should it be approved, "on a not-for-profit basis for emergency pandemic use."
Despite that momentum, he said executives at the company "have not encountered any undue pressure" and would maintain "the rigorous requirements of research, development and manufacturing" to bring a safe and effective COVID-19 vaccine to the public.
Furthermore, he said, "we also appreciate that a two-dose regimen may have the potential for enhanced durability in some participants." Therefore, the company is planning to run a phase III trial with a two-dose regimen beginning later this year.