- British pharma AstraZeneca will press into clinical study a leukemia drug it thinks could help calm the overactive immune response seen in some patients with COVID-19, the latest example of drugmaker efforts to repurpose existing therapies for the fast-spreading disease.
- The mid-stage trial, which will recruit patients in the coming days in the U.S. and Europe, will test AstraZeneca's Calquence, currently approved for two blood cancers.
- Calquence blocks a protein that regulates the body's production of certain inflammatory markers, which can help reduce the spread of mutating B cells In leukemia and lymphoma. Citing early evidence, AstraZeneca will test whether Calquence can also reduce respiratory distress caused by so-called cytokine storms.
Initially, many of the existing drugs thrust into testing earlier this year as potential treatments for COVID-19 were antivirals like Arbidol and Avigan, or HIV medicines like Kaletra.
Increasingly, however, drugmakers are exploring whether their arsenals of medicines hold potential therapies for the fierce immune attack that can characterize the second phase of COVID-19 disease.
Cytokine release syndrome, or "cytokine storms," are most widely known as a side effect of cancer cell therapy. Whipped up by the engineered T cells infused into the body to fight cancer, the immune system goes into overdrive, spurring high fevers that can be potentially life-threatening.
Gathering evidence suggests this could be happening in late-stage COVID-19, too, although it's not clear how similar these cytokine storms are to the ones that afflict many CAR-T patients.
Studies are underway to test Roche's Acemtra as well Sanofi and Regeneron's Kevzara, both of which target an inflammatory marker called IL-6 that's thought to play a role in cytokine release syndrome. Actemra is approved in the U.S. to treat the condition in the setting of CAR-T.
Novartis, Incyte and, most recently, Eli Lilly, meanwhile, are exploring whether drugs blocking regulatory proteins called Janus kinases could have a broader, but similar effect. Lilly this week announced its therapy Olumiant would be studied in the National Institutes of Health trial currently testing Gilead's antiviral drug remdesivir.
AstraZeneca is betting on a different kind of kinase, called Bruton's tyrosine kinase, or BTK. Calquence inhibits BTK, and has been shown in trials to slow the growth of certain blood cancers.
The drug is associated with numerous side effects, however, including serious and opportunistic infections, which could pose a challenge in treating patients at risk of secondary bacterial infections following COVID-19.
In the study now being set up, AstraZeneca will first test Calquence paired with best supportive care against supportive care alone in hospitalized patients who are not yet in intensive care units or on mechanical ventilation. It will then test Calquence in those more advanced patients. Irregular heartbeat is also a noted side effect on the drug's label.
AstraZeneca claims it's never move quicker in setting up a study.
"This is the fastest clinical trial that I've seen ever designed in my career of over 30 years," said Jose Baselga, AstraZeneca's head of cancer research and development, in a video posted online by the company. "So something that would have taken many weeks, if not months, came together in less than a week."
The drugmaker hopes to enroll more than 400 patients across sites in the U.S. and Europe. Two physicians at the U.S. National Cancer Institute will lead the trial, AstraZeneca said.