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Clinical trial for ruxolitinib planned in fight against COVID-19

Treatment for rare blood cancers could temper cytokine storm in people with severe forms of the disease

by Bethany Halford
April 7, 2020


The structure of ruxolitinib.

Drugmakers Incyte and Novartis are gearing up for a Phase III clinical trial of their drug ruxolitinib to see if it can help patients with severe COVID-19, the respiratory disease caused by the new coronavirus.

Doctors think the compound might dampen the out-of-control immune response—known as a cytokine storm—seen in people with severe COVID-19. If the cytokine storm can be tempered before there is significant damage to the lungs, patients might not need ventilators or might need them for less time and could have a better chance of surviving the disease.

Plans for the randomized trial were announced April 2. The trial will compare the outcomes of about 350 hospitalized patients who either get ruxolitinib or the current best standard of care without the drug. Severe COVID-19 patients who are unable to enroll in a trial can still get the drug through a so-called open-label study, in which both the doctor and patient know it is being given.

Ruxolitinib, sold as Jakafi in the US and Jakavi elsewhere, is approved to treat certain rare blood cancers. The drug works by blocking enzymes in the JAK-STAT pathway, which is overactive in these blood cancers.

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“It’s probably the most common drug I use,” says Prithviraj Bose, a hematologist and oncologist at the University of Texas MD Anderson Cancer Center, who is not involved in the clinical trial. Bose explains that the JAK-STAT pathway is fundamental to many biological processes related to immunity and inflammation, including marshaling a cytokine response. Cytokines are signaling molecules produced by the immune system’s cells.

“Most cytokines actually signal through the JAK-STAT pathway,” Bose says. “They need the JAK-STAT pathway in order to exert their actions.”

Steven Stein, chief medical officer at Incyte, says the company has been studying ruxolitinib to accompany CAR-T therapy, which involves engineering a patient’s own T-cells to better detect and respond to cancer cells.

“One of the things that happens with those therapies, particularly when they’re effective, is that you get a cytokine storm,” Stein explains. Scientists at Incyte spent the past two years investigating whether ruxolitinib could ameliorate that overreaction without interfering with the CAR-T’s cancer-killing ability. What’s more, anecdotal reports from China and Italy suggest that people with severe COVID-19 have better outcomes when given ruxolitinib.

In recent weeks, Sanofi, Regeneron, and Roche have announced that they will try treating COVID-19 with drugs for rheumatoid arthritis that go after the cytokine known as IL-6. While those drugs block a single cytokine, ruxolitinib “could block a whole array of cytokines,” Bose says.

Although ruxolitinib is generally safe, it can suppress the body’s immune response. For that reason, Stein says, ruxolitinib “shouldn’t be used very early on when people are just infected and your body is revving up to fight the virus.” Instead, he says, it’s better to give the drug when the viral load has gone down but the cytokine storm is starting up, which can happen in the second week after infection.

“Can you give the therapy in the right window that prevents the storm, that prevents clinical deterioration, and that prevents needing ventilation?” Stein asks. “If we get to that, we’ll feel like we played a really big role here.”

“Everything right now is just sort of intuition and logic, and the proof of the pudding will be in the clinical trials,” Bose says. “But I think this is a promising development.”


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