Anti-malarial pills combined with an antibiotic failed to put Habeeb Ahmad on the path to recovery. Then doctors got him into a clinical trial of another unproven drug against covid-19. That, too, didn’t work.
But that request also has resulted in frustration, with Gilead, remdesivir’s manufacturer, saying it has been overwhelmed by requests for access and simply cannot satisfy them all.
As Ahmad’s family waits in limbo, similar anguish is playing out across the country as families compete for limited chances to try unproven treatments, some of which have been promoted by President Trump as “game changers.”
The lack of any drug or vaccine for covid-19 has triggered a surge of demand to try not just one, but two or even three medicines of unknown value against the global pandemic.
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“It’s desperate hope. These are very long shots,” said Arthur Caplan, a bioethicist at New York University’s Langone Medical Center.
Mejdi Ahmad, Habeeb Ahmad’s brother, who is a gastroenterologist and is closely monitoring Habeeb’s care, said medical staff should be prioritized for experimental treatments because they are risking infection by working in hospitals.
“I’m pleading on behalf of my family, and the families of health-care workers affected, including his 6-year-old son, who keeps asking me when his father will be coming home,” Mejdi Ahmad said.
“It’s quite shocking,” he said of his brother’s sharp decline from seeing patients in early March to being in an intensive care unit, with failing kidneys and unable to breathe, kept alive by machines. “It’s almost like you’re in a dream. Is this going to be over? When is it going to be over?”
Under “compassionate use” rules, doctors can seek permission from the Food and Drug Administration to try unapproved therapies for critical patients. But the regimen typically involves fewer patients over a longer period of time. In March, with the crush of coronavirus patients, Gilead briefly shut down compassionate-use access to remdesivir, its infectious disease drug that is still in development, while it devised a new plan to expand access.
The drug company’s decision to change the rules for compassionate use also blocked access for Michael Goldsmith, 34, of New Jersey, the father of children ages 6 and 9, said his wife, Elana Goldsmith.
Michael, an IT consultant, has been on a ventilator for 10 days at Hackensack University Medical Center, longer than Gilead’s criteria for access now permits, she said. She and her family have contacted senators from New Jersey and Florida for help, to no avail.
“It seems like my husband Michael has fallen through the cracks every step of the way,” said Elana Goldsmith. “Gilead is denying him a chance to fight this. … I know that he’s not alone, and we’re not alone in this fight to get the remdesivir.”
Consulting firm Avalere Health, which is tracking drug development related to the novel coronavirus, lists more than three dozen potential treatments. But few are in the later stages of clinical trials. The two most prominent are Gilead’s remdesivir, and Regeneron’s rheumatoid arthritis drug Kevzara (the drug used in the clinical trial in which Habeeb Ahmad enrolled), according to Avalere.
The Trump administration has pushed generic anti-malarial drugs through an FDA emergency authorization to distribute millions of doses across the country, despite limited evidence of effectiveness.
Gilead said it has provided remdesivir to 1,000 patients on a compassionate use basis, outside of clinical trials that are being sponsored by the company and the National Institutes of Health.
The company said on March 22 that it was forced to pause its compassionate use program because of the high volume of requests, and create a new program called “expanded access” to handle a larger volume of patients. It said on March 23 that “several hundred” patients had received the treatment under compassionate use, a number that it later revised to 1,000.
Gilead said early this week that it began rolling out the new, broader system March 27 at an undisclosed, limited number of hospitals. The revised program will permit doctors to obtain the drug without seeking approval for individual patients from the FDA and Gilead.
Ahmad felt sick with fatigue, cough and increasing shortness of breath starting March 14 and went to an urgent-care clinic March 17 to get a covid-19 test, which was positive, his brother said. Within two days he was on a ventilator at North Shore University Hospital on Long Island and his kidneys had failed, his brother said. He was also given drugs to keep his blood pressure up. (The infectious-disease doctor treating Ahmad at North Shore declined, through a spokesman, to comment.)
Habeeb was initially given the anti-malarial drug chloroquine combined with the antibiotic azithromycin, Mejdi Ahmad said. The combination therapy has shown some promise in very small, limited clinical studies, has been promoted by Trump, and is being widely used in U.S. hospitals, but it remains unproven. It has not worked on his brother, Ahmad said.
Habeeb’s doctors contacted Gilead on March 20 and asked that he be put into a remdesivir clinical trial or get the drug on a compassionate use basis, Mejdi Ahmad said. Gilead denied the requests, he said, because Habeeb was on a ventilator and was receiving the drugs to boost his blood pressure, which Ahmad said Gilead cited as “exclusion criteria.”
The next step on March 21 was to put Habeeb into Regeneron’s clinical trial of Kevzara. But there is a 20 percent chance that he received a placebo, his brother said. In what’s known as double-blind clinical trials, some patients are given a fake version of the drug as a point of comparison, to see if those who are given the drug have a better outcome.
With still no sign of improvement, Habeeb’s doctors asked Gilead a second time for access to remdesivir, this time only for compassionate use, and they received a second denial on March 25, Mejdi Ahmad said.
Gilead did not respond to a request to discuss Habeeb’s case.
According to the new protocol posted March 27 on the FDA’s clinicaltrials.gov website, patients with renal failure and drugs to boost blood pressure are excluded from eligibility, which could disqualify Habeeb.
“I know I speak for everyone at Gilead when I say how much we all wish we could help every patient in need,” company chairman and chief executive Daniel O’Day said in a statement March 28, responding to the huge demand for the drug. “Today we are working at speed to establish the temporary expanded access programs, while at the same time establishing the potential safety and efficacy of remdesivir and determining for which patients remdesivir may have activity.”
In a statement Tuesday, the company said: “Remdesivir has not demonstrated safety or efficacy to date and so there is an inherent challenge in identifying the appropriate target population for this investigational agent. From a safety perspective, we exclude patients who might be at higher risk for toxicity due to evidence of end organ damage.”
The emotional and difficult search for clinical trials and compassionate use programs is a routine part of treatment for doctors and patients with certain diseases, especially cancer and rare disorders in which approved treatments are limited. The phenomenon occurs sporadically in concert with infectious disease epidemics, specialist said. But the scale of the covid-19 crisis has pushed these struggles to unprecedented levels.
The limited supply of experimental drugs creates winners and losers, say ethics specialists. Because drugs are more likely to be used in academic medical centers and clinical trial sites, rural parts of the country can be left out, said Caplan, the NYU bioethicist. It’s similar to organ transplants, where patients who can afford to apply for organs at multiple transplant centers across the United States, and can commit to traveling quickly, improve their odds of receiving a transplant, he said.
Mejdi Ahmad said he has called everyone he can think of to help push Gilead to approve the treatment for his brother.
“If it were my brother or son or father, I would be just as frustrated,” said Kavita Patel, a primary care internist in Washington, D.C. and a former health policy aide in President Barack Obama’s White House, who was contacted by Ahmad.
She said she did not agree with Ahmad’s assertion that health-care workers should get priority in the compassionate use program. But she knows Gilead’s chief medical officer, Merdad Parsey, and asked him to ensure the company made a timely determination one way or another in Habeeb Ahmed’s case. She did not ask Parsey to approve the request, she said, because she did not believe it would have been appropriate.
“But the reality is that these are not drugs that had been proven and tested. … Americans should realize that just because there is a potentially promising therapy does not mean that everyone should rush out to get it,” she said.
“By putting this kind of false hope out there you end up being distracted from the complete picture of care,” she said. “As a doctor, I would say that’s an even more dangerous thing.”
