A third leading COVID program enters holding pattern as NIH pauses testing of Lilly’s mAb
NIH begins ACTIV-5 study of anti-inflammatory mAbs, plus Moderna starts rolling submission in Canada
The launch of NIH’s Phase II ACTIV-5 Big Effect Trial study of anti-inflammatory mAbs Skyrizi from AbbVie and Boehringer and lenzilumab from Humanigen to treat hospitalized COVID-19 patients has coincided with a pause on the agency’s Phase III study of antiviral mAb bamlanivimab from Lilly and AbCellera in the same setting.
The pause puts a third high-profile COVID-19 program in a holding pattern.
A National Institute of Allergy and Infectious Diseases spokesperson told BioCentury on Tuesday that the Phase III ACTIV-3 trial’s data safety monitoring board (DSMB) noted the study had “reached a predefined boundary for safety at day five” — a safety threshold set based on the difference between adverse events in the bamlanivimab (LY-CoV555) and control arms.
The agency, which said, “The DSMB recommended pausing enrollment out of an abundance of caution,” is continuing to collect safety and efficacy data and will review data again at a preplanned meeting on Oct. 26. During the meeting, it will recommend whether to resume enrollment in ACTIV-3, according to the spokesperson.
Eli Lilly and Co. (NYSE:LLY) said it supports the DSMB’s decision but did not provide details.
ACTIV-3 is testing the antiviral mAb plus Veklury remdesivir from Gilead Sciences Inc. (NASDAQ:GILD) to treat hospitalized COVID-19 patients.
NIAID added that the pause does not affect NIH’s Phase II/III ACTIV-2 trial, which is testing bamlanivimab in an outpatient setting.
The NIH division is also collaborating with Lilly on the mobile Phase III BLAZE-2 trial to prevent COVID-19 in exposed individuals.
The DSMB’s recommendation comes a week after Lilly said it had submitted an emergency use authorization application for bamlanivimab monotherapy to treat high-risk, mild-to-moderate COVID-19 patients in an outpatient setting. The company has rights to bamlanivimab from AbCellera Biologics Inc.
The pause comes a day after Johnson & Johnson (NYSE:JNJ) said it has temporarily paused dosing in its COVID-19 vaccine trials, including the Phase III ENSEMBLE trial of JNJ-78436735, because of “an unexplained illness in a study participant.” The case is being reviewed by an independent DSMB and J&J’s internal physician team.
Trials of AZD1222 from AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and the University of Oxford remain on hold in the U.S. following reports of adverse events in a U.K. trial; they have resumed in the U.K., Brazil, South Africa and Japan.
NIAID also announced Tuesday it had begun the adaptive ACTIV-5/BET trial of a single IV dose of Skyrizi risankizumab from AbbVie Inc. (NYSE:ABBV) and Boehringer Ingelheim GmbH; and three IV doses, each eight hours apart, of lenzilumab from Humanigen Inc. (Pink:HGEN).
Patients in the experimental arms and the placebo group will also receive Veklury.
Like the U.K. ACCORD trial, ACTIV-5/BET is designed to rapidly identify which treatments yield suggestions of efficacy and should be progressed to larger clinical trials, rather than to prove clinical benefit.
Skyrizi is a mAb against IL-23 approved to treat plaque psoriasis. Lenzilumab is an anti-GM-CSF mAb that Humanigen has in a separate Phase III study to treat COVID-19; it is also in a Phase Ib/II study to prevent CAR T cell therapy toxicity in diffuse large B cell lymphoma patients.
Moderna starts rolling submission in Canada
Also on Tuesday, Moderna Inc. (NASDAQ:MRNA) said it has begun rolling submission for mRNA-1237 to Health Canada. Supporting data include those from an animal challenge study and Phase I safety and immunogenicity data from volunteers ages 18-55, 56-70 and 71 and older; and the Canadian agency will assess new data as Moderna submits it. A readout from the Phase III COVE trial is expected in November or December.
GM-CSF (CSF2) – Granulocyte macrophage colony-stimulating factor
IL-23 – Interleukin-23