Novel Monoclonal Antibody Promising Against Hendra and Nipah Viruses

By Marilynn Larkin

February 11, 2020

NEW YORK (Reuters Health) - The monoclonal antibody m102.4, being developed to prevent and treat Hendra and Nipah virus infection, was well tolerated and safe in a first-in-human study.

These henipaviruses are emerging zoonotic viruses that affect multiple animal species and, in humans, result in often-fatal respiratory or neurological disease, or both, note Dr. Elliott Playford of Princess Alberta Hospital in Woolloongabba, Queensland and colleagues.

In the phase I study, 40 healthy adults were randomly assigned to five cohorts; in each cohort, six patients received m102.4 and two received placebo. Four cohorts received a single IV infusion of m102.4 -- either 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), or 20 mg/kg (cohort 4) -- and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 hours apart and was monitored for 123 days.

Eighty-six treatment-emergent adverse events were reported, with similar rates between the treatment and placebo groups. The most common treatment-related event was headache in 40% of the combined m102.4 groups (12 of 30 participants) and 30% (three of 10) in the pooled placebo group.

No deaths or severe adverse events led to study discontinuation.

Overall, pharmacokinetics were linear, with a median half-life of 663.3 hours for cohort 1; 466.3 for cohort 2, 397 for cohort 3; and 466.7 for cohort 4.

Elimination kinetics were similar in those receiving single doses or repeated doses, with a median elimination half-time of 472 hours.

No anti-m102.4 antibodies were detected at any time-point during the study, according to the report in The Lancet Infectious Diseases.

"This long-awaited phase 1 clinical trial suggests that the antiviral antibody therapy is safe and well tolerated to human adults as a post-exposure prophylaxis," Dr. Hossain Sazzad of the University of New South Wales in Sydney, author of a related editorial, told Reuters Health by email.

"The therapy might be more effective if is administered immediately following infection," he noted. "However, in a real-world outbreak situation in South Asian countries, delays in seeking healthcare are common, which leads to advanced clinical progression of disease and poses a greater risk of making the therapy ineffective."

"We have seen in Africa how Ebola virus has persisted for a long time, then suddenly emerged as a massive outbreak with high fatality," he said. "We are now seeing how a small amount of mutation in pre-existing Corona virus has emerged as a novel coronavirus (n-CoV) with pandemic potential."

"Similarly, Nipah and Hendra viruses are causing occasional small clusters and outbreaks with almost 100% case fatality in South Asia and Australia, in both humans and animals," he noted. "We do not want to see these Henipaviruses emerge as global pandemics in future. Therefore, we need enhanced surveillance and early intervention approaches."

Dr. Waleed Javaid, Director of Infection Prevention and Control at Mount Sinai Downtown in New York City, also commented in an email to Reuters Health, "Both Nipah and Hendra can cause infections in humans with high mortality. WHO has identified Nepah virus infection as a priority disease for research, so a treatment is needed. This study helps in determining (its) safety."

Dr. Playford did not provide a comment.

SOURCE: The Lancet Infectious Diseases, online February 3, 2020.