Drug dilemma: Ef­fec­tive but un­prof­itable

A med­i­ca­tion can be crit­i­cal to a few pa­tients — but not enough of them to sup­port pro­duc­tion

The Washington Post - - FRONT PAGE - BY CAROLYN Y. JOHN­SON

For the first six months of Chris­tian Mumm’s life, his fam­ily lived on high alert. Chris­tian, who has a ge­netic dis­ease that causes se­vere epilepsy, ex­pe­ri­enced fre­quent seizures — at his worst, one ev­ery 10 min­utes — that left him de­pleted and jumpy. His three older broth­ers and sis­ters tip­toed around the house in New Hart­ford, Conn., afraid that if they breathed the wrong way or clinked a dish too loudly, it would set off a storm in his brain.

Chris­tian’s mother, Erica Mumm, re­called one heart­break­ing day when her 9-year-old daugh­ter came to her in tears.

“I kissed him, Mommy, and he had a seizure,” her daugh­ter said. “I can’t kiss him any­more.”

Af­ter a half-dozen drugs failed to help Chris­tian, doc­tors sug­gested the fam­ily try one called Potiga.

The medicine has had a pow­er­ful ef­fect. Seizures that once struck mul­ti­ple times an hour now come once ev­ery five or six days. But the drug came with a dead­line: At the end of June,

Glax­oSmithK­line, the Bri­tish drug com­pany that sells Potiga, pulled it off the mar­ket be­cause of de­clin­ing sales, forc­ing fam­i­lies to stock­pile sup­plies or wean their chil­dren off a drug that dra­mat­i­cally im­proved their qual­ity of life.

The dilemma faced by par­ents whose chil­dren ben­e­fited from Potiga — and fu­ture fam­i­lies who po­ten­tially may never have ac­cess to the drug — high­lights the lim­i­ta­tions of drug com­pa­nies’ busi­ness model.

Drug com­pa­nies’ in­vestor­driven busi­ness model al­lows them to make risky re­search bets to de­velop in­no­va­tive drugs. But at the end of the day, it means prod­ucts that are es­sen­tial to sick peo­ple are be­ing made by busi­nesses.

That may leave few op­tions to small pa­tient pop­u­la­tions who de­pend on a drug.

“There are peo­ple who’ve al­ready been tak­ing the drug, and based on their per­cep­tions, it’s help­ing. I ac­tu­ally find this one more heart-wrench­ing,” said Ali­son Bate­man-House, an as­sis­tant pro­fes­sor in the di­vi­sion of med­i­cal ethics at NYU Lan­gone Health. “Yes, we re­al­ize you were get­ting ben­e­fits, but be­cause of fi­nan­cial re­al­i­ties, and just what we choose to do with our busi­ness, we’re not go­ing to make the drug any­more.”

Glax­oSmithK­line said it has re­cently been in touch with two fam­i­lies, in­clud­ing the Mumms, to find a way to make the drug avail­able. But the com­pany is not presently mak­ing com­mit­ments to fu­ture pa­tients, and its abil­ity to sup­ply the drug is not indefinite, be­cause the re­main­ing sup­ply will even­tu­ally ex­pire.

“We care deeply about pa­tients and re­al­ize that any time a medicine is re­moved from the mar­ket it can be chal­leng­ing,” GSK spokes­woman Sarah Spencer said in an email. “At this time, our fo­cus is on the very small num­ber of pa­tients who are cur­rently re­ceiv­ing the prod­uct.”

Chris­tian’s se­vere form of epilepsy stems from a mu­ta­tion in a gene called KCNQ2. That mu­ta­tion causes elec­tri­cal sig­nal­ing in Chris­tian’s brain to go hay­wire, and Potiga — though it was ap­proved as a gen­eral seizure drug for adults — had a unique mech­a­nism among epilepsy med­i­ca­tions. It worked by tar­get­ing the pre­cise bi­o­log­i­cal de­fect that was at the root of Chris­tian’s dis­ease.

Chris­tian still suf­fers de­vel­op­men­tal de­lays, but his qual­ity of life is vastly im­proved. On the drug, he can in­ter­act with his sib­lings. He bab­bles and can learn and build on sim­ple abil­i­ties, such as eat­ing by mouth and smil­ing.

Physi­cians who treat and study pa­tients like Chris­tian say Potiga is a quin­tes­sen­tial ex­am­ple of how 21st-cen­tury medicine is sup­posed to work. As sci­en­tists learn more about the bi­o­log­i­cal causes of dis­ease, they will be able to de­sign drugs or re­dis­cover old ones that treat not just symp­toms but also the root causes of ill­ness. Potiga was de­vel­oped and ap­proved to con­trol seizures in adults with epilepsy, but it came with a bonus — it worked in a new way, by tar­get­ing potas­sium chan­nels in the brain.

“Here we have 30 years of NIH-spon­sored and in­dus­tryspon­sored re­search lead­ing to the spe­cific un­der­stand­ing of a cat­a­strophic ill­ness. We have a drug that acts on that mech­a­nism,” said Ed­ward Cooper, an as­so­ciate pro­fes­sor of neu­rol­ogy and neu­ro­science at Bay­lor Col­lege of Medicine. Tak­ing it off the mar­ket “goes ex­actly against what our are ex­plic­itly try­ing to do, which is make avail­able pre­ci­sion medicines to ad­dress un­met med­i­cal need.”

Ac­cord­ing to a 2011 study in Phar­ma­coepi­demi­ol­ogy and Drug Safety, 118 novel drugs were with­drawn from the mar­ket be­tween 1980 and 2009. Only a fifth of them were with­drawn pri­mar­ily be­cause of safety is­sues.

The plight of fam­i­lies who de­pend on Potiga is far from com­mon, but it could be­come more so with the in­creas­ing recog­ni­tion that a medicine that fails one group of peo­ple may be crit­i­cal for an­other sub­group. There’s a ma­jor push in medicine to­ward us­ing science to iden­tify the set of peo­ple for whom a drug works.

But when drugs live or die de­pend­ing on com­mer­cial vi­a­bil­ity, mass-mar­ket drugs that don’t ful­fill their ini­tial pur­pose may not be avail­able.

From an­other point of view, Potiga is sim­ply not a very good drug — an epilepsy medicine that was only ever ap­proved for adults and turned out to have a big safety down­side.

Af­ter it was ap­proved in 2011, a scary side ef­fect that caused bluetinged skin and pos­si­ble vi­sion prob­lems was un­cov­ered, lead­ing to a se­vere “black box warn­ing” on the drug’s la­bel. The safety prob­lems made Potiga con­sid­er­ably less at­trac­tive than the other op­tions avail­able to the peo­ple it was ap­proved to treat — adults with epilepsy. The drug was never tested in chil­dren be­cause of the safety con­cerns and a hold on tri­als by fed­eral reg­u­la­tors, ac­cord­ing to Spencer, the Glax­oSmithK­line spokes­woman.

“No neu­rol­o­gist has be­come de­hy­drated for weep­ing tears over the re­moval of a drug with so much prom­ise and so lit­tle per­for­mance!” Robert Clancy, a pro­fes­sor of neu­rol­ogy at the Chil­dren’s Hospi­tal of Philadel­phia, wrote in an email.

Potiga sales peaked in 2013, at $14 mil­lion in U.S. sales, ac­cord­ing to data from Quin­tilesIMS, a com­pany that tracks health-care data — far from an­a­lysts’ orig­i­nal es­ti­mates that it could reach more than $200 mil­lion per year. When GSK an­nounced it would dis­con­tinue the drug last sumpol­icy-mak­ers mer, there were fewer than 500 pre­scrip­tions per month.

The Mumms have stock­piled as much of the drug as they could, spend­ing about $1,200. They have about three months of sup­ply left. In late July, they fi­nally got word that the com­pany would help them get ac­cess to the medicine, but they have no idea how long the com­mit­ment will last.

“If they can do this to my kid, they can pull any other drug off the shelf of your medicine cab­i­net and do this to any­one else, with­out a sec­ond glance,” Erica Mumm said. “These com­pa­nies have great power, and they shouldn’t be driven solely by profit. They do have an eth­i­cal re­spon­si­bil­ity to the pa­tient.”

Spencer said that GSK is open to dis­cus­sions with other com­pa­nies that may want to ac­quire Potiga but has not seen sig­nif­i­cant in­ter­est in the drug. She also noted that if a com­pany ac­quires the rights to Potiga, it would still be ap­proved only for use in adults.

Doc­tors can pre­scribe drugs for off-la­bel use as they see fit, but if the com­pany wanted to mar­ket Potiga specif­i­cally for a rare dis­ease, it would need to con­duct a trial to get ap­proval. It would have to get the hold on pe­di­atric re­search lifted.

Other than sell­ing the drug to an­other com­pany, there may be other op­tions.

“There are these re­ally niche mar­kets in the cor­ners of the phar­ma­ceu­ti­cal mar­ket­place that need ex­tra at­ten­tion,” said Aaron Kes­sel­heim, an as­so­ciate pro­fes­sor of medicine at Har­vard Med­i­cal School. “If there was a non­profit phar­ma­ceu­ti­cal man­u­fac­turer that wanted to jump in, this is the sort of place that could be a good pos­si­bil­ity.”

The cur­rent so­lu­tion is a piece­meal ap­proach.

Amy Buches has been told the com­pany will find a way to pro­vide the drug to her son, Stephen. The Buch­eses are one of the two fam­i­lies that GSK has agreed to help get the drug.

Buches said that she is per­son­ally sat­is­fied. “Yet, it is un­set­tling to know that there could be an in­fant born in the world this very mo­ment that would ben­e­fit from Potiga, but will not be able to use it,” she said in an email.

Mumm knows first­hand what it would mean to lose ac­cess to the drug.

In May, the Mumms — hav­ing heard that the com­pany would not be mak­ing the drug avail­able — be­gan to wean Chris­tian off Potiga. His seizures started up right away, mul­ti­ple times an hour.

Mumm was in de­spair. With­out the abil­ity to con­trol his seizures, the doc­tors were se­dat­ing her son. She emailed his pal­lia­tive-care doc­tor. What was she sup­posed to do? Bring her son home in a fog of medicine and watch him dis­in­te­grate?

Just a few weeks ear­lier, Mumm had been hope­ful, think­ing about start­ing a new kind of ther­apy that could aid Chris­tian’s de­vel­op­ment, thanks to the im­prove­ments she had seen while he was on the drug.

In­stead, she found her­self ask­ing if there would be a way to en­sure her son had a peace­ful death.

“I want to get all my ducks in a row with know­ing op­tions,” Mumm wrote.

Mumm de­manded that the doc­tors stop ta­per­ing his medicine, and her fam­ily went about se­cur­ing as much of the drug as they could stock­pile.

In July, com­pany rep­re­sen­ta­tives got on a con­fer­ence call with the fam­ily and Chris­tian’s med­i­cal team to find a way to give him ac­cess to the drug.

KEVIN HA­GEN FOR THE WASHINGTON POST

Erica Mumm with her 15-month-old, Chris­tian. His se­vere epilepsy ap­pears to be re­lieved by the drug Potiga, which Glax­oSmithK­line has pulled from the mar­ket be­cause it is used by so few pa­tients.

KEVIN HA­GEN FOR THE WASHINGTON POST

Erica Mumm feeds her son Chris­tian, who has se­vere epilepsy, as his fra­ter­nal twin, Con­nor, feeds him­self at their home in New Hart­ford, Conn. Glax­oSmithK­line has promised to help the Mumms get the drug Chris­tian needs de­spite its with­drawal from the mar­ket.

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