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Chimerix enrolls dying 7-year-old boy in pilot study, skirts ethical quandary

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By Jennifer Boggs
Managing Editor

After enduring a social media firestorm this week vilifying the firm for not providing its antiviral candidate brincidofovir to a dying 7-year-old boy on a compassionate use basis, Chimerix Inc. found a way to get the drug to Josh Hardy without setting a potentially dangerous ethical precedent.

The Durham, N.C.-based company launched an open-label pilot study designed to test brincidofovir in immunocompromised patients with adenovirus infections. Josh was enrolled Wednesday as the first subject in that 20-patient study. A pivotal phase III is expected to be a continuation of the pilot program.

At first glance, it seems a simple win-win for both sides. Hardy’s parents get access to a treatment that could potentially save the life of their son, whose immune system had been compromised following a round of cancer treatments. And, in the end, the social media pressure helped accelerate clinical trial protocol discussions with the FDA, noted Chimerix CEO Ken Moch, who found himself the subject of many angry blogs and tweets after reports of the Hardy family’s plight started flooding the internet.

“It’s been both complex and wonderful,” he said. Complex in that “so many difficult issues needed to be thought through” such as ethics, regulatory and product development issues, and “wonderful because of the intensely dedicated group of people working through all those issues to find a pathway to get the drug not just to Josh Hardy but to all Josh Hardys.”

Getting the drug to all patients was at the crux of Chimerix’s refusal to provide the brincidofovir on a compassionate use basis. Moch was quoted in various media outlets Tuesday enumerating the cost to the company, which would slow down the ongoing development of the oral nucleotide analogue lipid-conjugate drug, which began dosing in the phase III SUPPRESS trial last year for the prevention of cytomegalovirus infection in hematopoietic cell transplant recipients. (See BioWorld Today, Sept. 10, 2013.)

“People get lost in the dollar signs,” he told BioWorld Today. But the biggest impact would have been felt in terms of manpower and company resources.

Chimerix is familiar with compassionate use. Through an investigational new drug application in March 2009, the company provided brincidofovir to more than 200 patients. Another 200 received brincidofovir under a Biomedical Advanced Research and Development Authority program. After that, the company of 50 employees decided to focus efforts on getting brincidofovir to the finish line in preventing CMV infection as quickly as possible, Moch said.

The requests for compassionate use, however, kept coming in.

“Over the past two years, we’ve had literally hundreds of requests,” Moch said, including more than 80 for patients with adenovirus infection. And the company has turned them all down.

“From an ethical perspective, our goal had to be to find a pathway not just for a single patient, but for many,” he explained.

COMPASSION – FOR A FEW

Had Chimerix offered the drug to Josh Hardy after declining other such requests, it could have raised some ethical issues. It also could have opened the floodgates for the other requests, noted bioethicist Arthur Caplan. “How do you say no to others?”

Caplan, the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics and director of the Division of Medical Ethics Department of Population Health at the NYU Langone Medical Center, said he understood the concerns of the company and that they underscore problems with the compassionate use program in general.

Aimed at offering potentially life-saving therapies to patients who have exhausted all other approved therapies, compassionate use programs – or expanded access programs, in FDA parlance – can serve multiple purposes such as giving a last chance to a patient with no other alternative and bolstering a company’s relationship with the patient community.

But there are downsides, too. And not all of them affect industry.

The medical community often is not aware of compassionate use programs, leaving it at least partly to the patients and their families to seek out those treatment options. So the people who get access tend to be those “who yell the loudest and who are media savvy,” Caplan told BioWorld Today.

A 67-year-old patient who just suffered a stroke doesn’t make as compelling a news story, he offered by way of example. Then there are patients who are not familiar with social media channels or who simply don’t have regular internet access.

Plus, there’s the issue of cost. Insurance companies don’t reimburse for experimental therapies, so it’s either the company or the patient that foots the bill. In the case of Josh Hardy, the cost issue appeared irrelevant – the Max Cure Foundation reportedly offered to pay for the treatment – but patients who can’t afford treatment end up excluded.

The solution to that, Caplan said, would be for lawmakers to set up a fund for compassionate use programs. “We demand that Congress create that” and then the programs could be administered through a consistent process, open to all, rather than through “notes on Twitter.”

ADVERSE EVENTS STILL COUNT

But even if a fully funded initiative is set up, companies might still want to think twice before providing drugs on a compassionate use basis. Firms have to wonder if there are any adverse events noted in compassionate use cases, “will they be held against the drug?” Caplan said.

“The problem is these are people who are so sick,” he added. “Sadly, most compassionate use drugs don’t work.”

In a best-case scenario, an adverse event will result only in some bad press, as Pluristem Therapeutics Inc. discovered in 2012, when investors sent shares dropping after a news article disclosed the death of a pediatric patient receiving the company’s PLX allogeneic cell therapy. Last year, however, a serious allergic reaction in a phase II study prompted an FDA hold. (See BioWorld Today, June 5, 2013.)

Worst-case, the death of a compassionate use patient itself could prompt a clinical suspension, further delaying the drug or preventing its path to market altogether.

And Chimerix’s concerns about being overwhelmed by trying to accommodate compassionate use requests was valid, too, Caplan added, “because ultimately the goal is to get the drug approved.” It becomes an issue of pitting one patient’s needs against the needs of many.

If the ongoing phase III trial yields positive data, Chimerix’s brincidofovir could have applications in multiple viral indications. The drug, a broad-spectrum antiviral designed to block the replication of double-stranded DNA viruses, is being tested for its ability to prevent CMV infection as the primary endpoint in the SUPPRESS trial, but secondary endpoints are testing the drug in adenovirus, BK virus and herpes simplex virus.

Chimerix is not yet disclosing the endpoint for the recently launched pilot trial in adenovirus. For the pivotal phase III program, the endpoint likely will be mortality.

And as for the attacks on him on social media this week, Moch said he doesn’t blame the family for their tenacity and actually spoke with Todd Hardy, the boy’s father. “I told him if it were my child, I’d do exactly the same thing.”

As “intense and unexpected” as it may have been, “it did help accelerate the process.”

Shares of Chimerix (NASDAQ:CMRX) gained $3.74, or 18 percent, to close Wednesday at $24.54.