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Chasing After ‘Compassionate Use’

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Friday, October 7, 2016 - 09:45

By Jeffrey Greenfield, MD, PhD
Co-director, Children's Brain Tumor Project

As a pediatric neurosurgeon, I thought nothing could be more frustrating than a brain tumor that can’t be fixed surgically. As a neuroscience researcher, I thought nothing could make me more impatient than the deliberately slow pace we need to take as we untangle the mysteries of how these tumors start, progress, and ultimately claim lives.

I was wrong on both counts.

The scientific obstacles to finding cures are significant, but I see signs every day that we will overcome them. I co-direct the Children’s Brain Tumor Project here at Weill Cornell Medicine, so I see firsthand how we’re starting to make real progress against these tumors – not just in our lab but around the country and around the world. So when I come up against an obstacle that’s not scientific, not a molecular mystery we’ve yet to solve but rather a bureaucratic tangle that stands in the way, that's when I become truly frustrated and impatient. The parents of children I care for share those emotions, of course, but their level can rise beyond frustration to outrage. Earlier this week on Facebook we saw this demonstrated clearly.

Let me step back a moment for some background. Medical research is appropriately subject to very careful oversight on many levels. The FDA must approve new drugs and new clinical trials, and the standards for getting those approvals are extraordinarily high – after all, we don’t want to rush a drug with potentially serious side effects to market before it’s been thoroughly tested. I support the oversight processes because I know how important it is to keep an impartial eye on the work scientists do to protect the very patients we are trying to heal.

When that oversight becomes a drag on progress, however, particularly when it prevents doctors from taking a last-ditch chance against a fatal disease to save a child, then it may be time to rethink the way the process works. The science of brain tumor research has accelerated so much in recent years – an amazing development, to be sure – that it actually may be moving too fast to wait for the processes that are meant to safeguard patients.

I spoke about this issue in June, when Weill Cornell Medicine hosted the New York City Regional Cancer Moonshot Summit. Ours was one of many conferences held on a single day around the United States in tandem with a national meeting in Washington, D.C., organized by Vice President Joe Biden. Many of us involved in cancer research and care were invited to speak on promising new initiatives as well as the obstacles to progress, to help the Cancer Moonshot initiative identify priorities and find ways to overcome obstacles.

The topic of my talk was personalized medicine. I’ve been a champion of this new approach for years, and I believe that treating cancers individually is the key to successful cures. Using genomic sequencing to lay bare a tumor’s secrets, then using that information to attack it with the best possible weapons, holds enormous promise for advances in cancer care.

I spoke that day about a child I was treating, an 9-year-old boy whose malignant brain tumor we had sequenced.  The data from that sequencing led us to a startling discovery: The boy’s tumor showed a genetic mutation that had not been associated with his particular cancer before. Even more reason for excitement was that there is a drug designed specifically to target against cancers with this mutation. It was a rare opportunity for hope in a bleak situation, a dramatic example of how precision medicine can work — but the story hasn’t yet had a happy ending.

This drug has not yet been tested in children, so the manufacturer was reluctant to allow us to administer it to this patient. Let me put that another way: This child’s tumor has no known cure, and we have very little to offer him in the way of effective treatment, yet the best hope for him – an available drug that’s undergoing rigorous clinical trials in adult cancers – was denied him because it might cause harm. Ask any parent whose child has this tumor if they would take that risk, and I assure you they would all say yes. It is difficult to explain to a parents or a child that a rule meant to protect them now stands in their way.

Last week, the mother of that little boy shared an article about the Cancer Moonshot Summit on Facebook. The article recounted the story I had told about my anonymous patient, and of course she had recognized her son in it.

“Livid!!” she wrote in her post. “This ‘boy’ is our Chase!”

Her two brief lines sum up the problem better than almost anything else I can say. In the vast piles of paperwork and evidence and requirements, what’s missing is Chase. Not just a number, not a statistic, not a dot on a line graph, but a real child – a little boy with a loving family who deserves this slender ray of hope the drug offers.

Other parents of children with brain tumors were equally outraged.

“This is unconscionable,” posted one parent who recently lost a child to this disease. Another mom, this one of a current patient, said, “I just don't understand, this just upsets me to the core. I'm seeing my son fade away right before my eyes and it's hurtful.”

Yes, there is a process for fast-tracking requests in special circumstances, and we have applied for and hope to receive a “compassionate use” exception for Chase. But the “fast track” could still mean three to six months before such compassionate use is approved. When a child may not have those months, it’s heartbreaking to see him denied a treatment that may help.

The pharmaceutical companies we work so closely with are not the enemy in this story. They are doing heroic work daily and are working towards the exact same goals that we are. They are, however, constrained by significant rules and regulations, which impede the real-time live interface between science and medicine that we are beginning to experience in 2016. This is what precision medicine promises, and we have to do better to deliver on this promise.

Here’s how we may be able to move the needle: The regulatory processes that burden companies are terribly slow and need to be revamped. We should push legislature for new mechanisms and incentives to allow and encourage companies to focus on pediatric cancers — even though these cancers may be rare and the drugs not profitable. Not a single new agent has been FDA approved for malignant brain tumors in children in the past 25 years. This needs to change.

What we need is not just a “fast” track that takes up to half a year, but a “now” track for truly extraordinary circumstances like this one. We need to come up with ways for regulatory processes to keep pace with scientific discoveries, and to allow scientists and oncologists to be more nimble. Every day we find more clues in genetic data, and some of them could lead to immediate action… if only we were allowed to take that action.

Orphan diseases don’t claim “enough” lives each year to make new drugs economically feasible to develop.  Ask Chase’s mom how many kids are enough. She knows the answer: one.