On the one hand, odds are very high that I’m dying of brain cancer. On the other hand, I’ve put myself in the bleachers figuring out why it’s so hard for those of us with glioblastoma — and other incurable illnesses — to quickly get treatments supported by some science.
Not long ago, I moved from the bleachers to the playing field. I took part in a presentation given to the staff of the U.S. Food and Drug Administration. What happened there was an education for me. And may be some help for others tied to a sickness like mine.
For the past 40 years, as a professional journalist, I’ve had ethical limits on what I could say in public. So my recent advocacy-based presentation to the federal FDA staff was like a first skydive. How would I land?
Four highly credentialed experts and I took our best shots proposing a new policy. But even greater attention about brain cancer, also known as GBM, from the recent diagnosis of Sen. John McCain is unlikely to produce fast policy changes.
Even a new FDA commissioner, the massive 21st Century Cure Act passed last year, and President Donald Trump — all aiming to loosen some regulations — may not affect the FDA’s approach. But maybe?
Median survival for my glioblastoma is about 15 months. (I’m more than eight months in.) Fewer than 20,000 such cases show up in the U.S. every year. But there are tens of thousands of patients with other fast and incurable illnesses who face similar treatment problems.
It’s absolutely vital to prevent too-common quackery from easily fleecing patients. But too slow an FDA process to approve new treatments creates its own dangers: Maybe too much of a delay for patients with a fast, incurable illness. Maybe an economic bomb for pharmaceutical companies, killing the testing and approval.
Like climbing Mount Everest
Which made that FDA staff event even more relevant. The experts I was invited to join had detailed knowledge of brain cancer, medical data collection and the potential power of a changed approval policy. They loaded their presentations like the metaphorical equivalent of climbing gear carried to a Mount Everest base camp.
The ascent would be very high and hard, but maybe this was the place to get the move started? Or would the carefully i-dotting, t-crossing group of FDA workers tell us we were pushing too hard?
The fellow who invited me to the meeting knew it was not a small request. “This is the most ambitious thing I have ever done in my whole time for this,” said Al Musella. “By far. Like an order of magnitude.”
Musella is a foot doctor and tech geek who founded what became the nonprofit Musella Foundation for Brain Tumor Research & Information before his sister-in-law died of GBM. She was diagnosed in 1992.
He discovered there was no easy way to search out current and experimental treatments. Musella used, no kidding, the first major commercial online service provider, CompuServe, to start his process in the early ’90s.
He set up an online support group and organized information that patients and their doctors could grab and use. Not that there were great choices. But his sister-in-law lasted an unusual eight years.
Standard FDA approval is a slow and steady process, he learned over time. Phase 1, 2, and 3 clinical trials are key. Lots of the earliest trials show treatments would be harmful — and that kills the studies. Or the trials show no major effect in Phase 2 despite the seemingly good theory — and that kills the studies. The Phase 3 alone costs many millions of bucks — and sometimes shows that the earlier trials weren’t accurate.
The studies are good at filtering out treatments that don’t work — and blocking quackery from too many medical grifters trying to steal panicked patients’ money.
Success of multiple treatments
But that’s not the only effect. Here are some negatives for glioblastomans:
Testing only one treatment at a time may be a failure because there's growing evidence that multiple treatments may be much more successful against GBM — with drugs produced by more than one competitive company.
The data can be hidden by aggressive companies paying for the work. Progress or failure can be a secret for months or years, making it impossible for other patients or doctors to evaluate those treatments.
And there's the time, the time, the time. The GBM median of 15 months MAY set my life span. IT IS a number I ignore at my own peril. If newest experimental treatments show progress but need to wait until the end of Phase 3 for FDA approval — and for insurance coverage of those hideously expensive new choices — I will probably be long dead before they hit their finish lines.
Musella is an expert on all of this. He and some of his buddies have been noodling a way to shift the FDA process: Require a new Phase 1 equivalent with at least 50 patients. See if it creates data that shows some likely actual boosts in survival — or likely biological benefits that may boost survival odds.
If so, get the FDA to issue a “conditional approval.” Any patient who gets a “conditional” treatment would have all data about the results collected and added to a government-controlled database — one that will be made public every six months. So doctors and patients and other researchers will be able to see progress or the lack thereof, and shift their own treatment choices if the evidence is clear.
That evaluation system would vastly speed availability. It would cut costs. It would reduce the staff time in evaluating every treatment. It might boost data far above only the 5 percent of relevant patients that generally join clinical trials.
And it would be a gigantic shift in FDA policy.
Eventually, the FDA commissioner would need to approve all of that. But first, the staff would need to consider the idea. Musella successfully pushed an agreement for a direct meeting that was set for a late June afternoon in a frigid conference room inside an office building in Silver Spring, Md., near Washington, D.C.
Musella was at the top. But his other top choices included stars in their own rights: the deputy director of the brain tumor center at Duke Cancer Institute; the founder of a California not-for-profit network of patients, doctors and scientists; and a brain tumor specialist from Children’s Hospital of Philadelphia.
Living with cancer
And finally, me. A Miami native, a professional journalist since 1981, a Dallas Morning News reporter for 29 years. Someone who lived through two other serious cancers and Type 1 diabetes long before my GBM diagnosis in December 2016. And now semi-retired because of my no-kidding long-term disabilities.
My role for this meeting, Musella explained, was to get the FDA staff emotionally connected. Whether or not our specific details were ready to roll, the staffers needed to understand why they needed to change policy.
The room was stuffed with about a dozen staffers. They included MDs and tech experts. Evaluators of medications and treatment mechanisms. Database nerds and close focusers on the FDA’s legal responsibilities and limits.
The top staffer in the room was Dr. Patricia Keegan, the FDA’s director of the Division of Oncology Products 2. She started at the FDA in 1990. She’s analyzed a ton of possible treatments. Some were successes, others failures.
Here’s an example of the change we were hoping for:
Dr. John Yu wasn’t in Silver Spring that day. He was at work at Cedars-Sinai Medical Center in Los Angeles. He’s a neurosurgeon and cancer researcher who fired up a company called ImmunoCellular Therapeutics several years ago. His sad news release was issued about a week before our FDA meeting.
ImmunoCellular killed its Phase 3 study of something called ICT-107. The Phase 1 study, Yu told me, had six of 16 patients live for more than eight years! That’s a 37 percent lottery ticket jackpot list of GBM successes. For patients who get the standard GBM treatments, only 5.5 percent live as many as five years.
But a Phase 2 trial with 120 patients only showed a clear advantage of about three months survival. The researchers thought they might be able to boost that, however. So it was time to try a Phase 3. It would take about five years and $100 million.
And investors absolutely will not offer that much capital, Dr. Yu told me. So the Phase 3 died, along with the chance of me and others getting access to it from an FDA approval.
Searching for a cure
Musella’s PowerPoint at that meeting had a title: “A proposal to speed up the search for the cure of brain tumors, while slashing costs and maintaining safety. Version 40.” No kidding.
Some highlights:
A cure probably will require a simultaneous combination of multiple treatments — which the FDA makes difficult.
While about 5.5 percent of GBM patients these days are surviving five years, there are a couple of current experimental treatments that might push that to more than 20 percent.
"Conditional approval" could include mandatory participation in a "virtual trial" with its own data-collection and distribution app.
Eliminating the Phase 2 and Phase 3 requirements would save about 99 percent of development costs and would cut about eight years from many first-access evaluations.
His list of current possible treatments that could benefit quickly from a faster approval came across as seemingly random letters, syllables and numbers: Val-083, DC-Vax, MDNA55, Trans Sodium Crocetinte. And yes, the now-dead trial for ICT-107.
The rest of our squad presented data examples and demonstrations of databases. Showed how this proposal would not only speed patient access but could get more information out to a much larger set of other researchers and oncologists. And poked mostly gently at the current FDA system.
An FDA demand of near-perfection, the Duke Cancer Institute scientist noted, would ignore the imperfection of many high-achieving people: Babe Ruth was famous for his 714 home runs. He struck out 1,330 times.
The FDA staffers mostly seemed to be listening closely. How could we be sure the data was accurate? How would the data be organized so it could be used without confusion and inaccuracy? Exactly who would be needed to run the hardware and software apps to make it work?
However, Dr. Keegan did not generally applaud. She was among the clearly intrigued, but that had limits, she said. “With regards to an alternative approval pathway, the issue that we would have is basically an entire change in the law,” she said. “So we are constrained.”
Maybe the massive 21st Century Cure Act offered enough flexibility, Musella said. The FDA would need a legal analysis, she said. “I’m not invested in a particular approval pathway,” she said. “What I have to do is follow the law.”
We have had two significant changes since the FDA staff meeting. One, an apparent opening from the staff. And two, a worsening of my condition.
The FDA staff wants another meeting, Musella said, with a discussion about how the proposal might apply to many kinds of illnesses. Not a small opening! Some members of Congress may be pulled into the process. Again, not small!
Our other team members had their own thoughts. Maybe their tech proposals can find medical audiences willing to demonstrate them? Maybe a new experimental treatment will show enough evidence that the FDA can be pressured? We shall see.
Cancer's return
My personal plans have shifted. My condition was not getting better even back then. I was already taking a lot of naps. I was having a little more trouble grabbing words for conversation. And my most recent head scan showed that the cancer is coming back, a recurrence as a tumor the size of a large grape. GBM grows fast. I’m matching the median at this point.
I was the last speaker at that FDA meeting. “Will all this work? You heard people who are a million times more knowledgeable than I about the tech, about how to use the database, about exactly what the benefit of the data might be,” I said. “But my meta point is that a system that will allow someone like me and my doctor to know when there are treatments that are even early in the study game that show enough evidence that it’s gonna improve my odds, that is what I need.”
The return of the cancer pushes my needs up even harder. I already have discussions set ASAP with neuro-oncologists at three major research hospitals about new, experimental treatments. But the still-slow FDA process may limit access for me.
My aggressiveness can’t be enough to get what I need — or what other patients need that’s similar to my target. Maybe that presentation to the FDA staff will result in some help.
It’s a small hope that I’m grabbing onto.
