Sanders, Cum­mings prob­ing FDA’s han­dling of Marathon af­ter a con­tro­ver­sial OK of old steroid for Duchenne MD

Rep. Eli­jah Cum­mings (D-MD)

Ver­mont Sen­a­tor Bernie Sanders and Rep. Eli­jah Cum­mings are tak­ing di­rect aim at the FDA to­day, crit­i­ciz­ing the agency for its red-car­pet treat­ment of Marathon Phar­ma­ceu­ti­cals as the bio­phar­ma com­pa­ny wound its way through the reg­u­la­to­ry re­view process, pick­ing up a lu­cra­tive ap­proval to use a cheap, gener­ic steroid as a high-priced brand­ed ther­a­py specif­i­cal­ly for Duchenne mus­cu­lar dy­s­tro­phy af­ter repack­ag­ing da­ta more than 20 years old.

The FDA has said be­fore that they sim­ply fol­lowed the rules in the way it han­dled this drug, OK’d as Em­flaza. But Sanders and Cum­mings, who has been lead­ing the charge in Con­gress to push Medicare to start ne­go­ti­at­ing drug prices, want to know if the FDA has a plan in mind to guard against com­pa­nies that want to game the sys­tem in search of big and easy prof­its. And they’re ask­ing the FDA for records that could ex­plain Marathon’s treat­ment, while point­ed­ly push­ing reg­u­la­tors to avoid a re­peat.

In ad­di­tion, the let­ter sug­gests that Marathon isn’t done ma­nip­u­lat­ing the sys­tem. The com­pa­ny has al­so ob­tained an or­phan in­di­ca­tion for de­flaza­cort as a treat­ment for pe­di­atric arthri­tis, the law­mak­ers say, putting it on track to po­ten­tial­ly ex­tend its stretch of mar­ket ex­clu­siv­i­ty and en­hance the drug’s fran­chise val­ue.

On Thurs­day morn­ing, though, Marathon an­nounced a sur­prise deal to sell de­flaza­cort to long­time Duchenne play­er PTC Ther­a­peu­tics for $140 mil­lion plus roy­al­ties. And the law­mak­ers may now have to shift their fo­cus as Marathon ex­ecs shun the spot­light. But the con­tro­ver­sy is un­like­ly to end, es­pe­cial­ly as PTC will now come up with a new price which is al­so like­ly to out­rage the Duchenne com­mu­ni­ty. And reg­u­la­tors will have to en­dure some ad­di­tion­al scruti­ny as well.

“A re­view of a num­ber of the doc­u­ments re­lat­ed to the orig­i­nal Uni­ver­si­ty of Rochester ap­pli­ca­tion for or­phan drug sta­tus and ear­li­er clin­i­cal tri­als has raised se­ri­ous ques­tions about FDA’s de­ci­sion re­gard­ing Em­flaza….” they write in the let­ter. “The fact that FDA award­ed Marathon a PRV and or­phan drug sta­tus with­out the com­pa­ny con­duct­ing sig­nif­i­cant re­search of its own un­der­mines the goals of these in­cen­tives. What process­es does FDA have in place to en­sure pri­vate com­pa­nies are not ma­nip­u­lat­ing a sys­tem meant to in­cen­tivize re­search for treat­ments of ex­treme­ly vul­ner­a­ble pa­tient pop­u­la­tions?”

What fol­lows is a laun­dry list of ques­tions for act­ing com­mis­sion­er Stephen Os­troff, in­clud­ing:

— Is it stan­dard prac­tice for FDA to re­ly on 20-year-old ef­fi­ca­cy da­ta and, if so, how many times has this hap­pened in the last 15 years?  If this is not a stan­dard prac­tice, is Em­flaza’s ap­proval an ex­cep­tion?

— Did any FDA em­ploy­ees raise any con­cerns about grant­i­ng Marathon the ben­e­fits of or­phan drug sta­tus or a PRV (pri­or­i­ty re­view vouch­er) for Em­flaza? Please pro­vide copies of mem­os, e-mails, or records of any such cor­re­spon­dence or doc­u­men­ta­tion.

The law­mak­ers’ staff al­so tracked the own­er­ship of the de­flaza­cort da­ta, not­ing that the work was orig­i­nal­ly fund­ed by Mar­i­on Mer­rell Dow, which merged, merged again and even­tu­al­ly wound up un­der the con­trol of Sanofi. From the let­ter:

— Giv­en this lengthy chain, what ev­i­dence did Marathon present to FDA re­gard­ing the in­tegri­ty of the decades-old ef­fi­ca­cy tri­al da­ta?  What in­for­ma­tion does FDA have re­gard­ing how Marathon came to ob­tain the 1995 da­ta?  Did FDA take any steps to ver­i­fy the va­lid­i­ty or in­tegri­ty of the chain of cus­tody of this in­for­ma­tion or ver­i­fy the old da­ta?  Please ex­plain.

The law­mak­ers picked over a string of sto­ries on the is­sue, in­clud­ing ar­ti­cles I’ve writ­ten about the es­ti­mat­ed price of de­vel­op­ment and more.

So far, most of the heat gen­er­at­ed by the con­tro­ver­sy over Marathon’s de­flaza­cort ap­proval has been di­rect­ed at the com­pa­ny and its CEO, Jeff Aronin. Sanders, an out­spo­ken crit­ic of the phar­ma in­dus­try’s pric­ing prac­tices, is spear­head­ing a dif­fer­ent kind of at­tack to­day aimed at reg­u­la­tors who hand­ed Marathon every plum a de­vel­op­er could want. And he’s clear­ly wrapped it in the kind of barbed lan­guage that would make it less like­ly for reg­u­la­tors to do it again, for an­oth­er com­pa­ny.

The sto­ry about Marathon and its cam­paign on de­flaza­cort has trig­gered a hot-tem­pered re­sponse among a va­ri­ety of De­mo­c­ra­t­ic law­mak­ers who see this as yet an­oth­er ex­am­ple of the kind of price goug­ing that a grow­ing list of bio­phar­ma com­pa­nies have en­gaged in. And this one is a stand­out.

De­flaza­cort is an old steroid that’s sold out­side the US for rheuma­toid arthri­tis and all the usu­al af­flic­tions as­so­ci­at­ed with steroid use. A num­ber of par­ents in the US have been buy­ing it from a UK sup­pli­er for about $1,000 a year, sat­is­fied that it’s the best choice for strength­en­ing chil­dren crip­pled and even­tu­al­ly killed by Duchenne mus­cu­lar dy­s­tro­phy, par­tic­u­lar­ly as it’s linked to less weight gain than ri­vals.

Marathon, though, priced de­flaza­cort at $89,000 a year af­ter the FDA ap­proved it, trig­ger­ing a tem­pest in the Duchenne com­mu­ni­ty. The com­pa­ny main­tained that it did the “heavy lift­ing” re­quired for a US ap­proval, cit­ing its re­search pro­gram and vow­ing that they would need years of sales to re­coup their in­vest­ment. But the tri­al ex­perts we talked to came up with de­vel­op­ment bud­gets that would make this drug quick­ly prof­itable, even with just a frac­tion of the mar­ket.

Along the way, the FDA re­ward­ed Marathon with some ma­jor ad­van­tages. There was an or­phan des­ig­na­tion, which comes with sev­en years of mar­ket ex­clu­siv­i­ty. There was al­so a pri­or­i­ty re­view vouch­er which can now be sold for more than $100 mil­lion — the vouch­ers, which can cut four months off of any drug re­view, have fetched as much as $350 mil­lion — which could eas­i­ly be enough to pay for the en­tire de­vel­op­ment pro­gram by it­self.

The out­cry has forced Marathon to pull back, at least tem­porar­i­ly paus­ing the launch of de­flaza­cort while talk­ing it over with mem­bers of the close­ly-knit Duchenne com­mu­ni­ty. It’s un­like­ly, though, that it can come up with a price like­ly to sat­is­fy par­ents al­ready pay­ing a dis­count price for over­seas sup­plies.

The FDA in the past has said that it han­dled this case as it would any oth­er, guid­ed by the rules laid out by Con­gress. Sanders, though, says the FDA got played, and he wants it to stop.

Pres­i­dent Trump re­cent­ly named Scott Got­tlieb as the head of the FDA. And if he gets the Sen­ate nod, as ex­pect­ed, he can set­tle in with a con­tro­ver­sy sit­ting on his desk.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

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In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

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Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

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George Yancopoulos (Regeneron)

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Petros Grivas, the principal investigator of the supporting Phase III JAVELIN Bladder 100, called the approval “one of the most significant advances in the treatment paradigm in this setting in 30 years.”

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Merck has notched an approval for using Keytruda to treat a biomarker-based subset of first-line colorectal cancer patients with unresectable or metastatic tumors, as the pharma giant continues to find new niches for its blockbuster PD-1 star.

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Vas Narasimhan, Novartis CEO (Patrick Straub/​EPA-EFE/​Shutterstock)

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