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Gilead, without details, says COVID-19 drug clears crucial clinical test

An experimental Gilead drug helped patients hospitalized with COVID-19 in a closely watched clinical study, the drugmaker said Wednesday, offering a tantalizing sign that antiviral treatment could curb the disease’s assault on the body.

Detailed data from the trial, run by the U.S. National Institutes of Health and viewed as the most rigorous test of the therapy’s potential, were not immediately available.

Bolstering the announcement, though, were findings from a Gilead-led study of severe COVID-19 patients, which the company also disclosed Wednesday. Unlike NIH’s, Gilead’s trial was not placebo controlled, and therefore results from the study are harder or, some argue, even impossible to gauge appropriately.

For its test, Gilead compared five- and 10-day treatment regimens of remdesivir, as the drug is called. Measured by time to clinical improvement, patients appeared to do equally well on either regimen, showing signs of improvement in either 10 or 11 days.

By the two-week mark, more than half of the roughly 200 patients in each group were discharged from the hospital. Gilead said the drug was relatively well tolerated, although 3% of patients discontinued treatment due to signs of liver toxicity and 7% of those treated overall stopped taking remdesivir.

The results are the first complete data to come from a slate of mid- to late-stage trials testing remdesivir. While scores of repurposed drugs have been pushed quickly into testing, and dozens of research efforts to find new ones are now underway, remdesivir has been viewed as a near-term hope for battling back against a virus that’s led to more than 218,000 deaths globally through Wednesday.

Until now, information on how well remdesivir might work against the new coronavirus has trickled out in snapshots, first from a leaked presentation by doctors at the University of Chicago, then from summary results posted in error to the World Health Organization website.

Those disclosures presented conflicting, but incomplete, views of remdesivir’s effectiveness. The study data released by Gilead on Wednesday, by contrast, offers a more comprehensive look, though many questions about the drug’s potential remain unanswered.

On their own, the data aren’t clear evidence remdesivir works. Gilead set up the study without a control arm, instead comparing less or more drug. Without a group of untreated patients to measure against, the data showing patients improving after receiving remdesivir is much more difficult to assess.

“In a month’s time, we’ve had some promising results,” said Kevin Grimes, an infectious disease specialist and associate professor of clinical medicine at Houston Methodist, which is a site for the Gilead trial. “Whether those people would’ve gotten better with supportive care, we don’t know,” he added in an interview ahead of Wednesday’s data.

Gilead emplyoees unloading filled vials of investigational remdesivir

Permission granted by Gilead Sciences

 

Recent figures from New York City doctors, for example, showed about two-thirds of a group of some 390 adults with COVID-19 were eventually discharged and 10% died. And in a recent randomized clinical study, 78% of COVID-19 patients taking the HIV drug Kaletra improved after 28 days, but so too had 70% of those on placebo. Investigators concluded the therapy offered no benefit.

By comparison, 61% of the 320 patients treated outside of Italy in Gilead’s study were discharged by two weeks, while 7%, or 23, had died.

“There’s a critique to be had that Gilead classifies it as an efficacy study,” said Brian Skorney, a biotech analyst at investment bank Baird, in an interview before the data was announced. “The better way to look at it is as a large, data-generating compassionate use study.”

Still, the positive-seeming findings, coupled with news of the NIH study’s success, are likely to heighten expectations remdesivir could play a role in treating COVID-19, placing new pressure on the company and on regulators tasked with assessing the drug’s safety and efficacy.

Both will soon have more information in hand. A second Gilead-led study, in patients considered to be in moderate condition, is expected to deliver data from 600 patients by the end of May. Unlike Wednesday’s news, those results will show how remdesivir fares against standard of care.

The National Institutes of Health trial, meanwhile, is viewed as the most definitive, having included a placebo and stipulated both doctors and physicians be “blinded” to who is receiving treatment. In a Wednesday statement, Gilead said it understood that trial has “met its primary endpoint” and that the institute would be providing more detailed information in an upcoming briefing.

Randomized studies of Gilead’s remdesivir in COVID-19
Study sponsor Patient population Target enrollment Control arm? Status
Gilead Severe disease, not ventilated at screening 6,000 No Data on first 397 patients reported April 29
Gilead Moderate disease 1,600 Yes Enrolling, data due by the end of May
NIAID Hospitalized adults 440 Yes Enrolling, data due soon
Capital Medical Univ. (China) Severe disease 453 Yes Terminated early after enrolling 237 patients. Summary data were posted in error April 23
Capital Medical Univ. (China) Mild to moderate disease 308 Yes Terminated early due to low enrollment
World Health Organization Hospitalized adults At least several thousand Yes Enrolling, data after June
INSERM Hospitalized adults 3,100 Yes Enrolling, data after June

SOURCE: Company, clinicaltrials.gov

Gilead’s study wasn’t supposed to be the first trial of remdesivir to read out. When it began, Gilead was expecting it would follow two China-based studies and the NIH trial.

In a statement, Gilead said it chose to design its severe study without a control group in order to prioritize supplies of the placebo version of remdesivir that it had on hand for those three trials.

“Given three randomized, placebo-controlled trials with remdesivir were either underway or about to start at the time we designed the SIMPLE studies, our goal with these studies was to answer the question of treatment duration, comparing safety and efficacy with 5 or 10 days of remdesivir treatment,” Gilead said.

The urgent need for coronavirus treatments may push the FDA to prioritize expanding access to the drug, even with limited information. A similar scenario unfolded with the malaria pill hydroxychloroquine, two versions of which the agency authorized on an emergency basis, but one of those drugs was already approved for use in other conditions.

For the study Gilead reported on Wednesday, the company enrolled patients who were hospitalized with positive COVID-19 tests and showed some signs of respiratory difficulty. Anyone already on mechanical ventilation, the prevailing intervention for those suffering heavily from COVID-19, were initially excluded. So, too, were patients with signs of liver or kidney damage.

Such criteria are typical for studies, but may mean the group of patients tested in Gilead’s trial were relatively healthier than its severe classification suggests.

“If you look at the criteria here, they’re really not severe,” said Baird’s Skorney.

Gilead later amended the study, allowing for thousands more patients to be enrolled and adding a second cohort of patients who went on to receive ventilation. Data on those patients are not available yet.

The timing of treatment might be particularly important, doctors interviewed by BioPharma Dive said.

Remdesivir works by stopping SARS-CoV-2 from reproducing itself in cells it’s invaded, a mechanism of action that suggests giving it sooner in the course of disease could help patients more.

“What concerns me, and people in my field, is that ordinarily with a respiratory virus you’d want to interfere with viral replication very early before the virus has had a chance to do damage in the respiratory tract and the lung,” said Elizabeth Duke of the University of Washington and the Fred Hutchinson Cancer Research Center, in an April interview. Duke is an investigator in the placebo-controlled, NIH study of remdesivir.

An exploratory analysis of the trial data conducted by Gilead seemed to support that thinking. By the 14th day, 62% of patients who were treated within 10 days of symptom onset were able to be discharged from the hospital, compared to 49% of patients who were given remdesivir later.

Giving remdesivir earlier, though, would be difficult. The drug is administered intravenously over multiple days, which would be challenging to manage on an outpatient basis in hospitals overwhelmed with COVID-19 cases.

“When patients with COVID-19 are stable and do not meet inpatient admission criteria, we cannot offer them an IV drug; so it is important to find a drug that can be given in the outpatient setting as well,” said Neera Ahuja, division chief of hospital medicine at Stanford University School of Medicine, in an April interview. Ahuja is also working on the NIH study.

Even if remdesivir can help, multiple treatments will be essential for beating back an infectious disease with attacks the lungs, but also affects organs like the heart and kidneys, too.

Drugmakers are moving rapidly to test an array of existing therapies, as well as to launch development efforts for new antivirals and antibody-based treatments. Most of those efforts will in all likelihood come up short, given the difficulties of drug development. But the hope is, by later this year, some will show enough promise to buy time until a vaccine is available.

Six vaccines are now in human testing, a scientific achievement that shatters pre-pandemic norms for how long is required to design and validate new candidates. Anthony Fauci, the U.S.’s top infectious disease expert and head of the National Institute of Allergy and Infectious Diseases, has repeatedly set expectations of a 12- to 18-month timeline, although that is still exceptionally optimistic.

But success with remdesivir could provide a needed morale boost and carry broader scientific significance in the battle against the new coronavirus.

“If this works, it’s fantastic because that means there’s other antivirals that can work much much better,” Skorney ​said.

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