Coronavirus: Who gets access to scarce experimental drug?

No one yet knows if a Bay Area medicine can help save the lives of coronavirus patients.

Yet demand is so high, and desperation so great, that Gilead Biosciences is tapping into its old stockpiles, scaling up manufacturing and announcing new rules for who gets access to its promising but unapproved drug.

With little but supportive care to help sick people, global hopes are pinned on its experimental antiviral agent called remdesivir. Demand was further fueled by President Trump, who in press conferences has promoted remdesivir and other unproven drugs.

An exponential increase in requests for the drug “has flooded an emergency treatment access system that was set up for very limited access to investigational medicines and never intended for use in response to a pandemic,” according to a statement this week from Gilead, a Foster City pharmaceutical powerhouse.

Of all the drugs now under investigation for COVID-19 treatment, remdesivir is one that makes the most biological sense. It incorporates itself into the viral genetic code, interrupting reproduction. In animals and cell cultures, it has killed the pathogens MERS and SARS, which are genetically similar to the new virus.

This week, after giving away the drug to hundreds of critically ill patients under an emergency “compassionate use” program, Gilead announced it is shifting to a new distribution strategy. It is no longer accepting new individual “compassionate use” requests, except in cases of severe disease in children and pregnant women.

Instead it is building a new pipeline called “expanded access,” which will distribute the drug to large groups of sick patients through specific hospitals.

It will also continue sending the drug to researchers at Stanford, UC San Francisco and medical centers conducting clinical trials. These trials are limited in size, and only open to patients who meet certain criteria.

The families of very sick ill patients — many of whom were already in line for “compassionate use” access – say they’re running out of time. Fearing they’ll be cut off, they’re begging for whatever treatment they can get.

“We’re in limbo. I want it on hand,” said Lori Lewis of Palatine, Illinois, stunned by the sudden illness of her husband Grant Reffell, a once-healthy 55-year-old chiropractor who is now fighting for his life in an Intensive Care Unit. Initially, he only felt fatigued and never had a fever, shortness of breath or other classic symptoms. Now he has severe pneumonia.

Her husband was approved for the drug last week, but it hasn’t arrived. As soon as his blood pressure stabilizes, his doctor at Northwest Community Hospital in Arlington Heights, IL, wants to try it.

“They told us it should be here last Saturday,” said Lewis. Now they’ve been promised the drug by Friday. “I just hope and pray that this is the truth. I hope they are working around the clock and sharing how to make the drug with other manufacturers.”

The problem, said bioethicist Art Caplan of New York University’s Langone Medical Center, is that there just isn’t enough drug for everyone. It isn’t practical, he said, for drug companies to start mass producing an agent that might not ever be approved.

“You can’t build a factory to make an unlicensed drug,” said Caplan, who leads the NYU’s Working Group on Compassionate Use and Preapproval Access, which studies the ethics of access to investigational medical products.

“Gilead doesn’t have an unlimited supply,” he said. When a drug is still under investigation, “companies are almost always facing some sort of scarcity.”

The issue of preapproval access has long generated controversy, according to the NYU Working Group. There’s no constitutional right to these drugs.  And when companies grant access, they do not always do so in a fair or transparent manner.

It’s an issue that’s been confronted by patients with other deadly diseases, Caplan said. For example, there was a shortage of the Janssen drug called Darzalex after early indications that it helped treat an aggressive bone cancer called multiple myeloma.

Remdesivir was created by Gilead during the West African Ebola outbreak of 2013 to 2016. It worked in cell cultures and in animals. But in people, it was a flop.

Now the drug has been repositioned as a treatment for coronaviruses.

“There is some theoretical advantage to using it,” said Dr. Aruna Subramanian, clinical professor of medicine and infectious diseases at Stanford University School of Medicine, who is involved in three remdesivir trials launched March 14.

Gilead expects some early results from its China trials in late April. In an unrelated development on Wednesday, the drug company bowed to public pressure to drop its bid for “orphan-drug status” for the drug, which could have limited affordability and blocked generic competition.

While no conclusions can be drawn from individual recoveries, anecdotal reports are driving demand.

In January, in the first known U.S. case of the illness, a man in Snohomish County, Washington, improved after receiving a single treatment.

Palo Alto resident Monica Yeung Arima, hospitalized this month with pneumonia after contracting the COVID-19 virus on a cruise in Egypt, began to improve after five days of intravenous treatment.

“It’s not a toxic drug. It’s generally well tolerated, which is amazing,” said Dr. Peter Chin-Hong, professor of medicine at UCSF, who is managing patients with COVID-19, including some who are critically ill, and has requested remdesivir for compassionate use.

“When you think of a drug like that — if it’s not going to cause a patient that much harm and you have a little evidence of benefit and the patient might die without treatment, of course you want to use it as much as you can,” he said in an interview with Infectious Disease News. “Scientifically, we always want evidence. But the risks are very low, as we know them.”

The first clinical trial began in February with passengers of the Grand Princess cruise ship treated at the University of Nebraska.

The new trials — four in the U.S. and two in China, involving hundreds of patients — started in early March. They study the effectiveness of the drug in patients with moderate or severe disease, with patients randomly assigned to receive different doses of remdesivir or a placebo.

“Compassionate use” access is much more logistically challenging, said Caplan. Designed to help seriously and terminally ill patients with no approved treatment options, it requires drug companies and federal regulators to review each individual patient request. The drug must get sent to far-flung patients. And because no data is collected, no one knows if it’s working or not.

“It’s a huge undertaking. You may be sending it to people who have no idea how to use it,” said Caplan. “And you have to get it there. Imagine sitting at a desk trying to figure out how to ship it to someone in Oklahoma.”

“Basically, you’re just trying to rescue people. You’re throwing them a life preserver in hopes they live,” he said. “You don’t learn anything.”

The multi-patient “expanded access” process is more efficient and meaningful, Caplan said. And the application for physicians is streamlined, so the drug could be shipped faster.

But only certain medical centers are designated as distribution centers, so not every patient, everywhere, will have access. Gilead has not said how large this program will be.

To prepare, Gilead is tapping into stockpiles of the drug that were created during West Africa’s Ebola outbreaks, as well as a stockpile of the ingredients needed to manufacture it. It is making two formulations, liquid and freeze-dried. It is expanding its network of manufacturing partners and has started its own internal production of the drug.

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“We’re investing tens of millions of dollars today, hundreds of millions of dollars in the very near future to scale up manufacturing facilities to make this happen,” said Gilead’s chief executive, Daniel O’Day at a briefing in early March.

“We’re investing heavily in our supply chain and manufacturing,” he said, “such that — should it work — we can respond immediately.”