As drugmakers mobilize to repurpose existing medicines for COVID-19, Eli Lilly is hoping its arthritis med Olumiant could play a part.
The Indianapolis pharma has kicked off a phase 3 clinical trial testing whether Olumiant can cut the rate of death or the need for ventilation or other oxygen support in 400 hospitalized patients, it said Monday. Data from the trial, expected in the next few months, will complement those from the NIH-run ACTT-2 trial, which is combining Olumiant with Gilead Sciences’ remdesivir.
The drug, which Lilly licensed from Incyte, works by inhibiting JAK1 and JAK2, thereby controlling inflammation in arthritis patients. The hope is that the same mechanism could be helpful in treating COVID-19.
Patrik Jonsson, president of Lilly Bio-Medicines, told FiercePharma that Olumiant could represent a “very important first step” toward reducing mortality for patients hospitalized with COVID-19.
“It’s not going to be the final step,” he said. Instead, antibody therapies or vaccines would represent that "final step" toward defeating COVID-19, Jonsson said. Lilly has started two antibody trials in recent weeks.
For the phase 3 study, Lilly is planning to enroll patients in the U.S., Europe and Latin America and anticipates opening sites where “we see a spike or significant increase” in infections.
If the data show an effect that’s “significantly better” than existing options, such as Gilead's remdesivir, Lilly would “sit down regulatory bodies across the globe … immediately."
In severe COVID-19 cases, the immune system may overreact against the virus, launching a potentially life-threatening condition known as a cytokine storm that can damage the lungs. Other drugs have been turned toward dampening that immune response, including Roche’s IL-6 inhibitor Actemra and AstraZeneca’s BTK inhibitor Calquence.
Olumiant (baricitinib) has been approved by the FDA to treat moderate-to-severe active rheumatoid arthritis since June 2018, and it sold $427 million in 2019. Lilly promises an adequate supply of Olumiant in both its current indication and potential COVID-19 use should clinical trials prove successful.
The idea that Olumiant could work in COVID-19 was raised by artificial intelligence drug discovery firm BenevolentAI.
In a study published in February in The Lancet, a BenevolentAI team suggested Olumiant could not only reduce inflammation but also block the virus from entering and infecting lung cells by inhibiting a protein called AAK1.
Two other JAK inhibitors—Bristol Myers Squibb’s Inrebic and Novartis and Incyte’s Jakafi—were later ruled out by the team as “unlikely to reduce viral infectivity at tolerated doses, although they might reduce the host inflammatory response through JAK inhibition,” according to a study in The Lancet Infectious Diseases. Nevertheless, Novartis is running its own Jakafi studies in COVID-19 focused purely on its ability to control cytokine storm.
Lilly will find out whether the AI prediction translates into real clinical benefits. The phase 3 trial will mainly compare the proportion of patient deaths or ventilation by day 28 between Olumiant and placebo. Investigators will also measure other outcomes, including clinical improvement, time to recovery and duration of hospitalization.
Besides Olumiant, Lilly is working on two investigational neutralizing antibody drugs specifically designed to target the novel coronavirus. The first project with AbCellera has just been pushed into phase 1, and last week, it licensed Chinese firm Junshi Biosciences’ candidate, eyeing potential combination of the two in a cocktail.