The storm started with a single Facebook post from a desperate mom. “Please help us save our son,” it began. Josh Hardy, the writer’s 7-year-old boy, had contracted a deadly viral infection while being treated for cancer. A potentially lifesaving drug was in late-stage clinical trials, but the company developing the drug, Chimerix, had refused requests by Josh’s doctors to provide it. “Basically they are not going to save a child’s life for money,” Aimee Hardy wrote, urging people to share her post.
And with that, everything changed for Kenneth Moch ’76.
The drug, called brincidofovir, was the lead product for Durham, N.C.-based Chimerix. The antiviral had indeed shown some potential to treat the type of virus that had infected Josh, called an adenovirus. But the company’s ongoing clinical-trial program wasn’t an option for Josh, for several reasons. Chimerix was studying the drug’s ability to prevent — not treat — the reactivation of another pathogen, cytomegalovirus, in adults. That was the path that Moch, the company’s CEO since 2010, considered the most direct way to win approval from the Food and Drug Administration — and so the most worthy of the time, money, and resources necessary to conduct a significant clinical trial.
Josh’s doctors at St. Jude’s Children’s Research Hospital in Memphis, where the boy was in intensive care, wanted Moch’s company to provide brincidofovir under an FDA program — commonly called compassionate use — that permits companies to provide unapproved, investigational drugs to seriously ill patients under certain circumstances. Chimerix previously had run such a program for brincidofovir, but its dedicated government funding ran out in 2012 and the company stopped providing the drug, hunkering down to focus on FDA approval. The hundreds of requests for compassionate use of the drug since then were, like Josh’s, denied by the company’s medical-affairs department. Moch had never heard of Josh Hardy or his denial until his story started gaining traction on social media.
And boy, did it catch on. The original Facebook message was posted March 6, 2014. The next day, the family set up a Save Josh Hardy Facebook page. The Twitter hashtag #SaveJosh began to accompany tweets, many of them hostile, urging Chimerix to provide the drug. A retired trial attorney named Richard Plotkin took up the cause, reaching more than a million people through the social-media feeds of his childhood-cancer nonprofit, the Max Cure Foundation. “I decided I was going to get this kid the drug or I’d destroy Chimerix and Ken Moch,” says Plotkin, recalling his thinking then. The Hardys’ hometown newspaper, the Fredericksburg (Va.) Free Lance-Star, picked up the story. Then came the national media: CNN the night of March 9, Fox & Friends the next morning. A typical headline: “Company denies drug to dying child.”
By this time Moch was personally caught up in the maelstrom, trying to make Chimerix’s case to Plotkin and, through the media, to the rest of the world. “There’s an absolute moral dilemma here,” Moch says a year later, remembering his thinking during the crisis. “Let’s accept that as parents, we’d do what [Josh’s mother] did,” he says. Moch has known plenty of cancer patients, and he knew what Josh was going through. “It broke my heart,” he says. “You want to help these kids, but if you stop and help each person along the way,” fewer may benefit in the long run. As CEO of a public company with 55 employees and limited resources, his job was to get the drug to market as quickly as possible, using the official clinical-trial process, so many more people could benefit. “It wasn’t about saving Josh Hardy; it was about saving many Joshes,” he says. His efforts to explain that, however, were no match for the story of the ailing boy in the ICU.
On Monday, March 10, Chimerix executives and board members received 15,000 emails and 3,000 phone calls, some of them threatening, says Moch. He felt he couldn’t give in to the external pressure. “It would have been a lot easier to just give him the drug,” he says. “But if you say yes to one person, how do you say no to everyone else?”
The compassionate-use program Josh Hardy’s supporters wanted to tap grew out of the AIDS crisis of the 1980s, as desperately ill patients clamored for anything that might buy them time against the deadly new disease. Restricting the use of experimental drugs to double-blind clinical trials — in which neither the patient nor the treating doctor knows whether the new drug is being administered — wasn’t enough, said writer and AIDS activist Larry Kramer. The trials “are ludicrously inhumane when two-thirds of this room could be dead in less than five years,” he said in a 1987 speech. That year, the FDA changed its rules to allow for emergency or single-patient use of experimental drugs under certain circumstances. Now formalized by FDA policy, the programs allow for patients with serious or immediately life-threatening conditions to seek out treatments that have passed the first stage of clinical trials in humans when there’s no other good alternative.
But while the FDA is involved in the process, it’s not the gatekeeper. Before a physician goes to the FDA to seek approval for a drug’s use, the company must be willing to provide it. Once that happens, the FDA’s stamp of approval is all but assured; in fiscal years 2010–2014, the agency approved 99 percent of the requests it received. Still, there are many reasons a company might opt not to provide a drug. “The more I talk to people at companies, the more overwhelmed I am by what they’re overwhelmed by,” says Richard Klein, director of the FDA’s patient-liaison program. The company may not have enough for compassionate use on top of the regular clinical-trial process. Or it may not have the personnel to dedicate to a compassionate-use program. Or it may be short on cash, as are many smaller biotechs with only one product. In theory there are ways to charge patients for certain costs associated with the drug’s manufacture and handling; in practice, companies give the drugs away.
The issue has become a big one for the pharmaceutical and biotech industries, as the number of requests has skyrocketed. Last year 1,882 requests reached the FDA, a 93 percent increase from 2013; scores more probably were denied by companies and never reached the agency. The Internet has fueled patients’ ability to check companies’ drug pipelines for potential treatments and to share information, and the right-to-try movement has advocated very publicly for the rights of terminally ill patients to access experimental drugs via state laws.
And then there’s social media, which can amplify a single patient’s request into a trending Twitter hashtag and recruit thousands of people to the cause. That social-media outpouring, Moch says, features a “staggering” rush to judgment and resembles a “public temper tantrum.” It leaves no room for a measured discussion of what even Richard Plotkin, Moch’s adversary in the Josh Hardy case, now admits is far more complicated than he first thought.
For one thing, experimental drugs are just that — experimental, notes Moch. While they may have potential, their effectiveness hasn’t been proven and their safety is a question mark. Only about one in 10 drugs that start the first stage of human trials ultimately wins FDA approval, according to a study that spanned 2004 to 2010. (The meningitis vaccine that Princeton students were given access to during the 2013–2014 campus outbreak was provided under expanded access, but that vaccine already had been licensed in Europe and Australia and was awaiting a final decision by the FDA. It was later approved.) The Josh Hardy case was rare in that case reports and earlier-stage trials actually suggested that brincidofovir might work for his circumstances.
“The question is, how high a bar, and what kind of a bar, do you want to have?” says Robert Klitzman ’80, a professor of psychiatry and director of the master’s in bioethics program at Columbia University. “If no patient can use a drug until it’s really proven to be safe, you’ll have people clamoring to try it.” And if the bar is too low, patients may be even less likely to get something that works, and more likely to be harmed, he says. Very easy access also opens the door to quacks who might seek to take advantage of desperate patients and their families, says Norman Fost ’60, professor emeritus of pediatrics and bioethics at the University of Wisconsin.
After all, the only real way to know if a drug works is to do the clinical studies. And a series of individual patients accessing a drug via compassionate use doesn’t equal clinical research, says Moch. Klein, of the FDA, agrees; the point of the program is to provide access to drugs, not test them, he says. The duties of the physicians who treat those patients don’t include gathering extensive data or monitoring the patients as in a trial. “We really don’t want to burden them with all those requirements,” he says. But as a result, little is known about the benefits of drugs acquired through expanded access — even a statistic as simple as how many people live or die.
Physicians who treat patients with compassionate-use drugs are, however, required to report any serious side effects that appear connected to the medication. And therein lies another industry fear. By definition, patients who are taking drugs under compassionate use are seriously ill. What if a death caused by something else raises a red flag at the FDA, holding up the entire clinical-research program? Klein says the FDA staffers who review these reports “are very aware that these people have run out of other alternatives, and have late-stage disease or multiple diseases,” and so might experience adverse events caused by their medical problems, not the drug.
An ongoing FDA analysis of almost 9,000 expanded-access requests from the past decade has found only two cases in which a company’s clinical trials were interrupted after an adverse event in a patient who received the drug as part of compassionate use. In both cases, the trials were allowed to proceed within a matter of months. But Moch believes an unrelated side effect in a patient receiving a drug through the program is bound to significantly hold up or halt clinical trials at some point: “It will have a chilling effect and will kill a good drug.” Public companies may face other consequences, too. Brincidofovir was given to Thomas Duncan, the Ebola patient in Dallas, last fall; when Duncan died, Chimerix’s stock fell.
Industry leaders worry that compassionate-use programs may draw patients who otherwise would look to enroll in their randomized trials but don’t want to risk being assigned to the control group that does not get the new treatment, says Robert Maguire ’72, a pediatric oncologist who spent about 30 years at both big pharmaceutical and small biotech companies. “That is a real issue,” he says.
A separate question is how a compassionate-use program should divvy up a limited supply of drugs in an equitable way. Before Josh Hardy’s request, Moch and others at Chimerix had received emails asking for the drug, including requests from people who pulled in politicians or other influential backers to plead their case. “What are the parameters of access?” wonders Moch. As Art Caplan, a New York University bioethicist and one of the few people to publicly support Chimerix during the crisis, wrote at the time: “Josh is cute as can be. He owns a puppy. He is getting his care at a famous hospital ... where the hospital knows all about what is in the drug pipeline. His parents are young, vocal, and good on television.” But what about older patients, or those not familiar with social media, or those whose doctors aren’t well connected?
Even as Moch was defending Chimerix’s decision, his company was working behind the scenes with the FDA to find a solution — something it couldn’t discuss publicly. In less than 36 hours, the agency approved the creation of a brand-new trial for brincidofovir, with Josh Hardy as its first enrollee. It would be open-label, which meant everyone would get the drug and no one would get a placebo. Chimerix announced the move in a press release on the evening of March 11. Still, that night, Moch and his wife checked into a hotel using assumed names and under guard, because the threats against him had grown credible.
Chimerix’s solution seemed like a win-win for the company. Josh Hardy got the drug, and the company provided it in the framework of a clinical trial, so data would be collected. Though the trial was sparked by the social-media frenzy, Chimerix didn’t give in to the demand under compassionate use, meaning it hadn’t set a precedent for granting other one-off requests. On its Save Josh Facebook page, his family celebrated and thanked Chimerix, “especially Kenneth Moch, whose skill, dedication, and expertise developed and made available this life-saving drug.”
Less than a month later, there was another Chimerix press release: Moch was out as CEO.
If that mystifies you, you’re not alone. A company spokesman says in an email that Chimerix cannot comment on an employee’s resignation. Moch says it was not his choice to leave but that the board, too, was traumatized by the social-media frenzy. He remains in North Carolina, where he had moved from New York to lead Chimerix. He’s consulting and planning his next professional move. But he’s also spending time on the compassionate-use issue, which is a hot one. After becoming “a lightning rod,” he now says he’s become “the accidental ethicist.”
At conferences and panels, representatives of the drug industry and government agencies are talking with patient advocates and ethicists to discuss potential changes to current policies. In addition to Moch, frequent participants include Richard Plotkin, whose Max Cure Foundation fueled the social-media pressure during the Hardy crisis. He’s come to realize, he says, that “as a pediatric-cancer advocate, I had a duty that runs not only to the child that I agree to help, but to the hundreds or thousands of children whose receipt of the drug might be delayed or made impossible if I’d put Chimerix out of business.” He and Moch have become unlikely friends.
In May, Johnson & Johnson said it would try something new: a pilot program involving an independent group of 10 medical experts, ethicists, and patient advocates to evaluate individual patient requests. The committee won’t have the final word — J&J still has decision power — but it will attempt “to make the process of listening to and processing requests much better than it was,” says Caplan, who will lead the new group. “We have two simple principles already: to try to anonymize the requests” to avoid social media and other pressure, and to have some kind of standardized policy online so patients can easily find information on a company’s program, he says.
But companies will face many questions as patient demand grows. Princeton professor Marc Fleurbaey, an economist who writes about theories of justice, suggests that pharma and biotech companies should have incentives to set aside a certain percentage of their drugs for expanded access. And of course, notes Klitzman, there’s the question of who will pay for compassionate-use programs if they become bigger. Should companies continue to foot the bill? The government? Health insurers? Individual patients, raising money via Kickstarter? Who will be liable if the drug does kill someone?
“There is no cookie-cutter solution,” says Moch. As he wrote in a Wall Street Journal op-ed in March, “Each drug is different, the testing and data required for FDA approval are different, and patient populations are different.” And it won’t always be as simple as implementing the Josh Hardy fix.
As for the little boy whose plight kicked off this discussion, he was regaining strength and working to rebuild his immune system, according to a March 12, 2015, Facebook update. (Family representatives didn’t respond to requests for comment.) The Save Josh Facebook page now advocates for St. Jude’s funding and raises awareness of compassionate use and pediatric cancer.
Brincidofovir is still moving down the path to potential FDA approval, Chimerix says. In August, the company said it had enrolled 200 people in the trial begun with Josh Hardy. It also said that preliminary results from the first 85 patients showed a mortality rate of less than 40 percent, compared to reported mortality rates for the infection that were as high as 80 percent.
And Moch? He’s not happy with leaving Chimerix, but that’s about it for regrets. He’s at peace with the decisions he made during those frantic few days in March 2014. “Over a year later,” he says, “I wouldn’t change a thing.”
Katherine Hobson ’94 writes about science and medicine.