Add another drugmaker to the list of those repurposing existing meds for COVID-19. AstraZeneca is now trying to turn a blood cancer drug against dangerous immune complications in seriously ill patients.
In what's been labeled the fastest launch of a clinical trial in the history of AstraZeneca, the British pharma will start testing Calquence to examine its effects on the potentially lethal immune overreaction storm associated with COVID-19 infection. The drug is currently approved in the U.S. for mantle cell lymphoma and chronic lymphocytic leukemia.
The decision comes after researchers at the NIH’s National Cancer Institute observed “some clinical benefit” of the drug’s use in a small number of hospitalized COVID-19 patients with advanced lung disease at the Walter Reed Army Medical Center, according to Forbes.
As the body’s immune system fights the novel coronavirus, the reaction can spin out of control in a phenomenon known as cytokine storm, which can cause serious lung damage.
Previous studies suggest that BTK, the oncogenic protein Calquence targets, is also a key regulator of the production of multiple inflammatory molecules in the lung. Therefore, BTK inhibition could theoretically reduce the release of these cytokines and dampen an excessive immune response. In real life, blood cancer patients who got BTK inhibitors also experienced decreased proinflammatory cytokines and chemokines, according to AstraZeneca.
The new trial, dubbed Calavi, will be conducted in two parts. The first will test Calquence on top of the current standard of care in patients who are hospitalized but not on ventilation or in intensive care. The second part will evaluate the regimen in critically ill patients in ICU. Because Calquence comes as a capsule, for those patients already on ventilators, AZ’s advising doctors to give the drug in a liquid solution made up of Coca-Cola to utilize the beverage’s acid property, according to Forbes.
The hope is to demonstrate that Calquence “reduces the need to place patients on ventilators and improves their chances or survival,” José Baselga, AstraZeneca’s oncology R&D chief, said in a statement on Tuesday. Baselga told Forbes that the company completed drafting the trial protocol and submitted it to the FDA within three days of receiving early evidence from NCI, setting a new record for the fastest launch of a clinical trial in the company's history.
The trial is expected to start enrolling patients in the coming days in the U.S. and several countries in Europe, AZ said.
As COVID-19 continues to wreak havoc across the globe, biopharma companies have been busy looking for inspiration from existing drugs in the absence of an approved treatment—and Calquence isn’t the first cancer med that’s been redirected that way.
Last week, Karyopharm Therapeutics said it would test its own blood cancer drug Xpovio—recently approved by the FDA to treat advanced patients with multiple myeloma—in severe COVID-19 patients. The drug blocks the protein XPO1, which the Massachusetts biotech said plays important roles in both the interaction of several viruses with host cells and the activities of pro-inflammatory molecules. Therefore, Karyopharm argues, it holds promise as a blocker of both viral replication and immune-related injury.
Johnson & Johnson’s Imbruvica leads Calquence as the current market leader in the BTK class. “We have received and reviewed proposals to conduct exploratory research studies to evaluate [Imbruvica] for the treatment of patients with moderate or severe COVID-19 requiring hospitalization,” a spokesperson for J&J's Janssen said in a statement to FiercePharma. “The investigators and institutions sponsoring the studies are in the process of registering the trials with the [FDA].” The spokesperson also stressed that the company's “first priority is to the patients living with B cell malignancies and chronic graft-versus host disease where [Imbruvica] is approved by health authorities,” as well as other ongoing clinical trials. BeiGene recently won an FDA nod for in-class competitor Brukinsa, and clinical data suggest it’s a safer option than Imbruvica.
In addition, Roche has also launched a clinical trial of its anti-inflammatory med Actemra to assess its potential in managing cytokine storm in COVID-19 after anecdotal efficacy stories from China, and its IL-6 inhibitor rival—Sanofi and Regeneron’s Kevzara—is also in two studies in the U.S. and Europe.
Eli Lilly, meanwhile, is enlisting its rheumatoid arthritis drug Olumiant in a master trial run by the NIH’s National Institute of Allergy and Infectious Diseases, hoping that the drug’s “anti-inflammatory activity” by way of blocking JAK could also be beneficial for patients hospitalized with COVID-19.