Eli Lilly Launches Phase III Trials of Baricitinib in COVID-19

Eli Lilly and Company reported it had enrolled the first patient in its Phase III trial of baricitinib in hospitalized adults with COVID-19. The drug is marketed as Olumiant for adults with moderately to severely active rheumatoid arthritis (RA).

The company plans to enroll 400 patients and will be run in the U.S., Europe and Latin America. It will include hospitalized patients who have at least one elevated marker of inflammation but who are not in mechanical ventilation.

The drug, an oral JAK1/JAK2 inhibitor, will be tested to see if it can decrease the incidents of the cytokine storm associated with COVID-19 infection. The drug may also inhibit the host cell proteins involved in viral reproduction.

The primary endpoint for the trial is the proportion of patients who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation by Day 28 in patients receiving 4 mg of Olumiant daily with background therapy compared to the placebo group (with background therapy). Key secondary endpoints include the percentage of patients showing clinical improvement at different times, time to recovery, length of hospital stays, number of ventilator-free days and mortality over a 28-day period.

“Lilly is committed to fighting this global pandemic, and this includes testing whether existing medicines including baricitinib could help treat the complications of COVID-19 in patients,” said Patrik Jonsson, Lilly senior vice president and president of Lilly Bio-Medicines. “This randomized controlled study is an important step in our understanding of baricitinib as a potential COVID-19 treatment.”

The data from this trial will complement results from a trial of Olumiant with Gilead Sciences’ remdesivir in the second phase of their Adaptive COVID-19 Treatment Trial (ACTT-2) that is being run by the National Institute of Allergy and Infectious Diseases (NIAID). It enrolled the first patient in May. It is comparing the efficacy and safety of the 4-mg daily dose of Oluminant plus remdesivir compared to remdesivir alone. Remdesivir is the only drug authorized for use in treating COVID-19, showing about a 33% decrease in recovery rates of the disease.

There are also other trials Lilly is supporting in North America and Europe in hospitalized COVID-19 patients.

“Following upon the success of remdesivir to treat moderate to severe COVID-19, hospitalized patients are still in need of novel approaches to reduce mortality,” said Vincent C. Marconi, professor of medicine and global health at Emory University School of Medicine and Emory’s Rollins School of Public Health. “Several ongoing studies with baricitinib will provide necessary data about this treatment that may combine antiviral activity with suppression of cytokine storm.”

In an interview with Reuters, Jonsson indicated that if the trial is positive, the company could possibly receive approval in the U.S. from the Food and Drug Administration (FDA) for this indication as early as August. For the combination with remdesivir, should they prove even more effective together, an approval could happen in July.

Jonsson also indicated the company has a drug specifically designed to treat COVID-19 that could potentially be authorized for use as early as September. This refers to neutralizing antibodies the company is testing.

On Monday, June 8, Lilly announced that its partner Junshi Biosciences had dosed the first healthy volunteer in a clinical trial of a neutralizing antibody against COVID-19. The company is testing a second antibody to test and is conducting preclinical studies of a third antibody. In an interview with Reuters, the company’s Chief Scientific Officer Daniel Skovronsky said the third antibody could possibly begin human trials in the next few weeks. One of the antibodies might be available for use by September.

“For the treatment indication, particularly, this could go pretty fast,” Skovronsky said. “If in August or September we’re seeing the people who got treated are not progressing to hospitalization, that would be powerful data and could lead to emergency use authorization. So that puts you in the fall time: September, October, November is not unreasonable.”

Monoclonal antibodies are used to treat cancer, rheumatoid arthritis and many other diseases. They are essentially immune cells that have been found to activate against a specific type of cell, whether it’s a specific type of cancer cell or a specific virus, in this case, SARS-CoV-2, the virus that causes COVID-19.

One advantage of the antibody approach is they are generally faster than the development of a vaccine. Even though vaccine development for COVID-19 is moving at an unprecedented pace, many things need to go perfectly for one to be available before the end of the year that is both safe and effective, and many experts question the likelihood of that happening.

Lilly’s two antibodies are LY-COV555, which is being developed with Canadian biotech company AbCellera. The second, JS016, is partnered with Chinese company Shanghai Junshi Biosciences. Both act by blocking the virus’s spike (S) protein that it uses to enter human cells.

Skovronsky indicated that the third possible antibody candidate acts on a different part of the virus, and most likely will be tested with one or both of the other candidates.

“It’s good to have two antibodies,” Skovronsky said. “The downside is that manufacturing is precious. We have limited manufacturing capacity. If two antibodies are required, half as many people will get treated. So our goal is to see if we can do one antibody at as low a dose as possible.”

If one of the antibodies is effective, the company has the manufacturing capacity to deliver hundreds of thousands of doses by the end of the year. However, the capacity isn’t enough for global distribution.

Skovronsky said, “Global capacity for antibodies is just not high enough that we could ever think about adequate doses” for “billions of people in the prophylactic setting.”

He went on to suggest that the best solution would be to widely inoculate individuals with COVID-19 vaccines when they become available and hold back antibody treatments for people who either have the disease or have recently been exposed to it. This, in particular, could help with vulnerable populations, such as nursing homes, where vaccines are less effective. Vaccines depend on the immune system being able to build an adequate response to the vaccine, which will then be able to mount a defense against the actual virus. The elderly and immuno-compromised may not always build enough response to the vaccine to provide effective defense.