The search for a treat­ment

Jour­nal­ist with brain can­cer ap­peals to FDA staff to speed up search for cure

The Dallas Morning News - - Front Page - By JEFFREY WEISS Staff Writer jweiss@dal­las­

Staff writer and brain can­cer pa­tient Jeffrey Weiss takes his quest for a treat­ment to the U.S. Food and Drug Administration.

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 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.

Climbing 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 sis­terin-law died of GBM. Her ill­ness 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.

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.

Seek­ing 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

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.

Cro­cetinte. And yes, the nowdead 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 nearper­fec­tion, 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 neu­roon­col­o­gists 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.

Louis beLuca/Staff Pho­tog­ra­pher

A4--94.1W4ioo1was among a group that re­cently ap­peared be­fore staff mem­bers of the Food and brug Ad­min­is­tra­tion, aim­ing to per­suade the agency to speed up the process for ap­prov­ing treat­ments for brain tu­mors.

File Photo/The As­so­ci­ated Press

Tk41m44pi­ni1p­k8p1Weiss and oth­ers at­tended about the treat­ment ap­proval process for brain tu­mors was held this summer at the Food and brug Ad­min­is­tra­tion cam­pus in Sil­ver Spring, Md.

AL1 bd­cELLA

Michael Hogue/Staff Artist

From left: Marni Weiss was with her hus­band, Jef­frey, in June when he and Drs. Henry Friedman, Al Musella, Marty Te­nen­baum and Adam Res­nick met with mem­bers of the FDA staff.


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