Tackling coronavirus is the next challenge for Penn cancer pioneer
“There are many redundant trials, not prioritized based on science but on companies’ portfolios,” Carl June said.
The coronavirus is giving a new direction to Carl June’s life — after menacing it.
June is the Penn Medicine researcher whose lab pioneered T-cell immune therapy, a revolutionary, albeit fabulously expensive, one-time treatment that has cured blood cancer patients who were terminally ill.
It turns out that the worst coronavirus infections often trigger an immune-system overreaction that is also a side effect of the T-cell therapy, now made by Novartis and branded Kymriah.
That’s why June is joining the pell-mell global race to find medicines for COVID-19, and publishing papers about likely candidates. Actemra, a rheumatoid arthritis drug that June’s team used as an antidote to Kymriah’s immune overstimulation, is now in clinical trials for severe COVID-19. And June has proposed a trial of cyclosporine, an immune suppressant long used to prevent organ rejection in transplant patients.
Lanky and fit at 66, June is also newly recovered from the disease that has killed more than 140,000 people worldwide. While he didn’t need to be admitted to the Hospital of the University of Pennsylvania, he felt as if he were “coughing up a lung.”
“I was sick for about three weeks,” said June, who before the pandemic regularly biked to work from his Merion Station home. “I don’t know where I got [infected], but I do a lot of traveling. My case was mild to moderate.”
He’s now trying to donate his plasma, he added during an interview last week. Penn is among many centers testing the theory that coronavirus-fighting antibodies in recovered patients’ blood plasma may help critically ill patients.
Coronavirus “has a way to outwit the immune system,” June said. “That’s why the illness drags on.”
Besides plasma, the mainstream media have focused on two other potential treatments: hydroxychloroquine, an anti-malaria drug that President Donald Trump has touted; and remdesivir, the experimental antiviral made by Gilead that was not effective against the Ebola virus.
But doctors around the world — especially in China, where the coronavirus emerged — are desperately trying a long list of other drugs, as well as alternative therapies. More than 500 clinical trials, and counting, are underway. There are so many that websites have been created to keep track, and to help recruit the millions of participants needed for the studies.
The fingers-crossed list includes antivirals that usually treat hepatitis C and the AIDS virus; anti-inflammatory drugs used for a lung-scarring disease; steroids and other immune-suppressants; cancer drugs that inhibit blood-vessel formation; cancer drugs that cut a brake on the immune response; stem cells; and experimental drugs in the pipeline for various conditions.
The urgency only heightens flaws in the drug-development process.
“There are many redundant trials, not prioritized based on science but on companies’ portfolios,” June said. “They use patients up. It doesn’t allocate basic resources wisely."
For example, he said, there are at least 16 trials of drugs like Genentech’s Actemra, also called tocilizumab. These drugs block one of the powerful inflammation-causing “cytokines” that send the immune system into overdrive.
Nearly eight years ago, a “cytokine storm” almost killed 7-year-old Emily Whitehead, the first child to receive the experimental T-cell therapy at Children’s Hospital of Philadelphia. She was days from dying of leukemia. But the therapy — made by genetically engineering her T cells to attack her cancer — sent her into a tailspin of organ failure.
June’s team saved her with a medical Hail Mary: Actemra, which is now approved to treat the cytokine storm. Emily’s 15th birthday is next month.
Actemra has relieved severe COVID-19 in a small study in China, and, anecdotally, in at least one dramatic case in the United States.
June said he’s confident Actemra will prove effective, “but they can’t afford it in India. They need something cheap.”
That’s the advantage of cyclosporine.
“Carl was particularly interested because it’s off patent, it’s affordable, there’s a good supply, and it could be very helpful in the developing world,” said Emma Meagher, Penn Medicine’s chief clinical research officer.
Penn’s ethics-review board is now considering June’s proposal for a small trial to see if giving cyclosporine to patients soon after hospitalization can prevent the immune overreaction.
But the risk-benefit trade-off is dicey, Meagher explained. The release of inflammatory proteins in COVID-19 is slower and less severe than with T-cell therapy, so reducing the body’s natural defenses could backfire, maybe upping the chances of pneumonia. And while lab studies suggest cyclosporine could reduce the virus’ ability to reproduce, it might actually do just the opposite.
For June, the coronavirus brings him full circle, back to infectious disease. The U.S. Naval Academy grad spent the early part of his career researching the AIDS virus alongside government scientists including Anthony Fauci and Deborah Birx, who are now leading the federal public health response to the pandemic. June is sanguine that the coronavirus crisis, like the AIDS crisis, will force changes for the better.
“I think we’re going to come out of this with lessons that help us change,” he said. “That’s the small silver lining.”