Eli Lilly launches PhIII JAK study, aiming for the first drug to lower mortality in Covid-19
Soon after the NIH announced in late April that Eli Lilly’s JAK inhibitor baricitinib would be the second drug tested in the trial that had proven remdesivir effective, doctors around the world began telling Lilly that that wouldn’t be enough.
Since the early days of the pandemic, the Indianapolis pharma had heard from doctors in Italy, Spain and elsewhere who, facing hospitals full of patients with a disease with no known treatment, used the JAK inhibitor — known commercially as the rheumatoid arthritis drug Olumiant — off-label. The doctors wanted to know conclusively if it worked. But the NIH trial could only tell them if, when combined with remdesivir, it worked better than remdesivir alone. And then only in the more severe patients.
“We decided it’s our obligation,” Eli Lilly Bio-Medicines President Patrik Jonsson told Endpoints News. “For scientific reasons but most importantly for healthcare providers and for patients, we needed to understand the overall effects of Olumiant/baricitinib alone in treating Covid-19.”
Lilly is now launching their own Phase III, 400-person study to test whether baricitinib alone can beat placebo in treating Covid-19. Spread across 15 sites in 4 countries, the trial will test the idea that the drug not only has potential to manage the cytokine storms that afflict late-stage patients, but also treat the disease in its mild to moderate manifestations.
Unlike some other major Covid-19 trials, including most notably the first part of the NIH study and several Gilead ran on remdesivir, the trial’s primary endpoint won’t be about time to recovery or how symptoms improve on an 8-point scale. Instead, the question will be simple: At day 28, is there a significantly fewer number of patients on the drug arm who have died or gone to ventilation than in the placebo arm?
“Since the community got the data on remdesivir in the beginning of May, we are setting the bar higher,” Jonnson said. “We need to add incremental value.”
The new Lilly trial joins a throw-anything-against-the-wall now covered in traditional Chinese and Indian medicines, immune blockers and immune boosters, anti-coagulants, and antivirals of myriad origins. Clinicaltrials.gov now lists 1,211 different interventional Covid-19 trials.
Still, researchers say there’s reason to believe that baricitinib has better odds than others. It was first identified as a potential treatment in February by the British biotech Benevolent AI as part of a machine learning-based drug screen.
“Baricitinib, being a JAK inhibitor, has some advantages on some of the other cytokine agents,” Vincent Marconi, an infectious disease specialist at Emory University, told Endpoints.
Like the Roche drug IL-6 blocking drug Actemra — which has shown potential in early studies — baricitinib blocks some of the cytokines, or immune signals, that can lead to an overactive inflammatory response in some patients. But unlike IL-6 blockers, Marconi said, baricitinib blocks several immune pathways as opposed to just one.
“The hope with a single cytokine therapy is that maybe you can get the critical one and that’s all that’s needed, and the other ones don’t play much of a role. We don’t know the answer to the yet,” Marconi said. “But with JAK-STAT inhibitors like baricitinib, we’re really targeting multiple of these cytokine pathways. I think that’s one of the main attractive rationales.”
With virus-neutralizing antibodies now entering human testing — including two from Eli Lilly — to great medical attention, Marconi said he could imagine a future where several of the most effective therapies were used in combination, as in HIV treatments.
Any coronavirus study will fluctuate with the case counts in trial site cities, but Lilly is hoping to have results by September. The NIH hasn’t announced a timeline, but the company said it is already more than half-enrolled.
Patients in the trial will still be able to take remdesivir if their doctors prescribe it, although patients would not necessarily fit criteria for both, said Patrick Milligan, an infectious disease specialist at the Community Health Network in Indianapolis, one of the study sites. Although guidance for remdesivir can vary state to state and even hospital to hospital, it is generally given to later-stage patients.
Milligan said his hospital has given baricitinib to Covid-19 patients since the early days of the pandemic and the patients who received it seemed to do better than those that got Actemra. But the results were hard to parse; the patients who got Actemra were generally already in worse condition.
”This is all anecdotal. It’s useful. If that’s the data you have, that’s fine,” he told Endpoints. But now they were joining the study “to hopefully help get some definitive answers.”
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