Doctors cut out part of her lung. They delivered radiation, immunotherapy, and chemotherapy. But Rose Fraenza’s stage 4 lung cancer proved to be stubborn.
In search of a new treatment, her doctors’ testing zeroed in on ulixertinib, an experimental drug designed to strike at genetic changes in her tumor. She volunteered for a clinical trial at Smilow Cancer Hospital, the clinical arm of Yale Cancer Center, to try ulixertinib. In March, doctors planned to enroll Fraenza. Then came Covid-19.
Across the globe, while research into potential Covid-19 vaccines and treatments is speeding along, the pandemic has slowed or brought to a halt clinical trials for other diseases. Clinical trials demand patient travel, doctors, and clinical space—all pinched by the rapid spread of Covid-19. By one count from the publication BioPharma Dive, more than 70 companies so far reported an interruption to at least one clinical trial because of the pandemic.
These delays could extend an already lengthy process to get drugs to market. And they may cut off a lifeline for patients willing to try a drug before it gets regulatory approval. A clinical trial can also be a way for a patient to ease their symptoms or provide an altruistic gift to scientific research. For Fraenza, she says, her eight grandkids need their nana.
During a FaceTime call from her living room in New Haven, Connecticut, Fraenza pulls out some family photos. She talks about how when her grandson was in elementary school, he loved coming over to watch scary movies. Now that he’s a teenager, they’ve graduated to cooking together. She holds up a photo of her twin sister at her hospital bedside after a surgeon removed part of two ribs and a cancerous lung lobe. The procedure vanquished Fraenza’s tumor, but the cancer later spread to her pelvic lymph nodes as well as her clavicle and femur bones. “Who lives long with stage 4 cancer?” Fraenza asks. “But this trial is another chance.”
Unlike many clinical trials that split patients into control and treatment arms, the ulixertinib study guaranteed all participants would receive the drug. Experimental drugs often flop in clinical trials. But ulixertinib, which was developed by BioMed Valley Discoveries, showed promise in an early-stage study with 135 cancer patients who had already tried other treatments. That led to the drug’s inclusion in MATCH, a 1,100-site study sponsored by the National Cancer Institute that pairs drugs with tumor mutations. (A spokesperson for BioMed Valley Discoveries, the drugmaker that hatched ulixertinib, said a representative wasn’t available to talk about how the clinical trial delay could affect the company’s business.)
“It’s likely the ultimate effect will be to reduce the rate at which we can complete the trials,” says Lyndsay Harris, associate director for the cancer diagnosis program at the National Cancer Institute. As for the timing of when stalled studies will resume, she says that will be determined on a case-by-case basis.
The freeze in clinical trial starts comes as physicians of all stripes are rerouted to handle a surge in Covid-19 patients. “Now we even have our oncologists working in the intensive care unit,” says Roy Herbst, chief of medical oncology at Yale Cancer Center. “These are very trying times.”
Fears abound over exposing patients to the virus, especially because many cancer drugs weaken the immune system to the point where it can’t mount a counterattack. Drugmakers, doctors, and ethics committees must weigh the risk of a clinical trial patient contracting Covid-19 against the benefits of a therapy. It’s not always clear-cut. “We’ve had to think about, how essential are these study visits?” asks Susanna Naggie of Duke University School of Medicine, who provides oversight of trials there. “Is the participant already receiving a medication that they cannot otherwise get? Is this a potential lifesaving medication?”
Sometimes, patients voluntarily drop out of studies that are midway through or in late stages to cut down on exposure to the new coronavirus, raising the specter of costly clinical trial reboots. (I recently covered this in an article about Covid-19 scrambling the biotech industry.)
Emma Meagher, chief clinical research officer for Perelman School of Medicine at the University of Pennsylvania, says there’s no telling when clinical trials will go back to normal. It depends on the severity of the outbreak—and how hard-hit a particular region is. And in the future, things won’t necessarily be the same. “I think we will become more careful and more thoughtful about what actually requires in-person visits versus remote visits,” she says.
For Sharon Terry, her 25-year quest to find a cure for her two kids’ rare disease just entered an unwelcome phase: navigating clinical trial headaches. In 1994, Terry suspected a reoccurring rash on her daughter indicated something more serious. Confirming Terry’s instincts, a dermatologist diagnosed both her daughter and her son with pseudoxanthoma elasticum, or PXE. The slow-onset disorder can obscure vision and cause a host of cardiovascular issues.
When scientists had few answers, Terry and her ex-husband formed PXE International, a nonprofit that orchestrates research into the disease. By 2000 the organization’s scientific partnerships successfully pinpointed the gene behind the mutation that causes PXE, but it took years to understand the disruption that ensues. It turns out, those with PXE have lower levels of an enzyme called pyrophosphate, causing calcification of elastic tissues.
Terry has long dreamed of the next step: early-stage clinical trials to assess a pair of potential PXE treatments. One study led by PXE International will analyze whether simply ingesting pyrophosphate—already approved as a food additive by the US Food and Drug Administration—helps PXE patients. The group also plans to support a biomarker study, followed by an early-stage clinical trial to assess whether an existing drug from Japanese pharmaceutical Daiichi Sankyo can fight PXE. But the pandemic has pushed back the studies, possibly by six to nine months. “When it was 1999 and 2000, we knew we were many years from a treatment,” Terry says. “And now, everybody was pretty hyped up, geared up and excited that we might be on the verge.”
But tacking a delay onto what’s already been a lengthy search comes at a cost. “Pushing it back means some people are going to have vision loss when we could have potentially had a treatment sooner,” says Ian Terry, Sharon’s son, now 30 years old. Ian describes himself as healthy but says he keeps his fingers crossed: The disease progresses with age.
With a surge in clinical trial disruptions, doctors who are still running studies are turning to desktops and tablets, virtual screenings, and uploading paperwork remotely. When possible, medications are being mailed, and health care workers travel to deliver home care. The FDA recently encouraged the pivot, noting that some trials could go virtual. Suddenly there’s willingness to “adopt technology that exists to run clinical trials in the 21st century,” says Greg Dombal, the chief operating officer of Halloran Consulting, which advises companies on clinical trials.“The world of clinical research is maybe 10 to 15 years behind most other industries in terms of adopting technology,” Dombal says, noting as an example that electronic signatures only became mainstream in this realm in the last year or two.
But many trials can’t be done remotely. For instance, IVs and in-hospital monitoring typically accompany CAR-T cell therapy that uses a patient’s modified blood cells to fight cancer cells.
For those eager to join upcoming trials, the disruption has been distressing—to say the least. Rene Roach pinned her hopes on an experimental cancer drug called cibisatamab, paired with other drugs. The stage-4 colon cancer patient took part in early screening for a clinical trial at Duke University School of Medicine. Then trial enrollment paused indefinitely. The culprit: Covid-19.
“I thought, ‘Maybe this is something that’s really going to help me, and who knows, maybe even cure me,’” Roach says. “But then I hear the study is suspended, and if I’m being honest, I cried.”
Roach, who is 50 years old and was diagnosed in 2016, considers herself healthy for someone with such a harrowing diagnosis. Earlier treatment blunted the cancer’s spread. As she sat on the back porch of her Maryland home, her red hair backlit in the early afternoon sun, she reflected by video chat on how this critical stretch of her life could unfold. She hopes that her current chemotherapy regimen keeps her stable until the trial starts back up. For her, the ideal scenario would be that a drug cocktail that includes cibisatamab assails the cancer, and later, surgery mops it up.
But Roach also laid out an unnerving possibility: In the meantime, her body could develop chemotherapy resistance, and with other promising clinical trials laid up, her options could narrow to third-line drugs known for nasty side effects.
In an emailed statement, representatives from Roche, the drugmaker behind the clinical trial, wrote: “The Covid-19 situation is dynamic and we are seeing some impacts on the continuity of certain clinical trials in all the regions where we conduct clinical studies. Our commitment to sites and patients is finding new and flexible ways to work.”
Meanwhile, Roach said she’s trying to keep positive: “It’s a tough situation, but we’re counting our blessings.” Behind Roach, cream-colored seashells from North Carolina’s Outer Banks were lined up on a ledge. She collected them with her family. Roach hopes the future holds many more trips with them.