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Product Development

Lilly’s Olumiant adds to remdesivir benefit in NIH COVID-19 study

Sep 15, 2020 | 1:25 AM GMT

Data from NIAID’s ACTT-2 study mark Lilly’s rheumatoid arthritis drug as the first targeted immunomodulator to succeed in a randomized, controlled Phase III study in hospitalized COVID-19 patients, and support combining immunotherapies with Gilead’s remdesivir to improve outcomes.

Not yet determined is whether the combination of Olumiant baricitinib and Veklury remdesivir reduced death.

Eli Lilly and Co. (NYSE:LLY) and Incyte Corp. (NASDAQ:INCY) announced Monday that oral Olumiant  reduced time to recovery by about one day when added to Veklury from Gilead Sciences Inc. (NASDAQ:GILD), meeting the primary endpoint in ACTT-2. The study defined recovery as no longer requiring supplemental oxygen or ongoing medical care, or hospital discharge by day 29.

Olumiant also met the the study’s key secondary endpoint, which compares outcomes on an 8-point ordinal scale at day 15. Detailed data, including COVID-19 severity in patients in ACTT-2, were not disclosed.

The pharma plans to discuss with FDA emergency use authorization for the oral JAK-1/JAK-2 inhibitor based on the readout. The EUA would authorize a 4 mg dose daily, which the pharma said is twice what FDA has approved to treat rheumatoid arthritis.

In May, the agency had issued an EUA for Veklury to treat hospitalized COVID-19 patients based in part on the Phase III ACTT study, also run by NIH’s National Institute of Allergy and Infectious Diseases, which had shown the antiviral reduced time to recovery vs. placebo by four days. The study did not show a significant survival benefit (see “Remdesivir’s Challenge”).

Lilly will also review the ACTT-2 data with NIAID to assess whether it will impact the pharma’s double-blind, Phase III COV-BARRIER of Olumiant in hospitalized COVID-19 patients.

Olumiant’s standing

Like ACTT, ACTT-2 is assessing day 15 and day 29 mortality as secondary endpoints; analyses of the survival data from ACTT-2 are under way.

Dexamethasone is so far the only drug to have demonstrated a survival benefit in a Phase III trial: the U.K.’s RECOVERY study in hospitalized COVID-19 patients. The generic anti-inflammatory steroid is approved for COVID-19 in the U.K. and is under review by EMA, but is not authorized in the U.S. (see “U.K. Approves Steroid”).

RECOVERY’s data for the broad immunosuppresive drug had underscored the case for anti-inflammatory drugs in treating later COVID-19 stages as it showed stronger effects in patients with more severe disease who required mechanical ventilation.

Dexamethasone’s success had contrasted sharply with July’s Phase III disappointments for anti-IL-6 mAbs Actemra tocilizumab from Roche (SIX:ROG; OTCQX:RHHBY) and Kevzara sarilumab from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Sanofi (Euronext:SAN; NASDAQ:SNY) (see “Second IL-6 Failure”“Data for IL-6 mAb in COVID-19 Disappoint”).

Actemra is in a handful of other COVID-19 trials including including the Phase III REMDACTA study of the mAb plus remdesivir. Kevzara is no longer in development for COVID-19.

Machine-learning validation

The data from ACTT-2 also validate BenevolentAI’s machine learning platform, which in early February predicted that the oral JAK-1/JAK-2 inhibitor could be repurposed for COVID-19 (see “BenevolentAI Deploys Machine Learning”).

BenevolentAI’s algorithms had suggested that in addition to its anti-inflammatory activity, Olumiant could have direct antiviral properties via binding at least one target required for viral entry. 

Patrik Jonsson, president of Lilly Bio-Medicines, previously told BioCentury the pharma had chosen to test Olumiant in ACTT-2 because evaluation under master protocol provides the fastest path to data and ultimately authorization; and because, based on the potential dual mechanism for COVID-19, partnership with NIAID was the best path forward (see “Why Lilly Chose NIH’s COVID-19 Master Protocol”).

TARGETS
IL-6 – Interleukin-6
JAK-1 – Janus kinase-1
JAK-2 – Janus kinase-2

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