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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.

Ad­comm splits slight­ly in fa­vor of FDA ap­prov­ing Chemo­Cen­tryx’s rare dis­ease drug

The FDA’s Arthritis Advisory Committee on Thursday voted 10 for and 8 against the approval of ChemoCentryx’s $CCXI investigational drug avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

The vote on whether the FDA should approve the drug was preceded by a split vote of 9 to 9 on whether the efficacy data support approval, and 10 to 8 that the safety profile of avacopan is adequate enough to support approval.

An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.

In­cyte ponies up $12M to set­tle char­i­ty foun­da­tion kick­back claims; US ex­er­cis­es op­tion for more dos­es of mon­key­pox vac­cine

One in a string of lawsuits targeting copay charity foundations, the DOJ has been hunting drugmaker Incyte for what prosecutors alleged was a kickback scheme to court patients. Now, Incyte is clearing its name.

Incyte will shell out $12.6 million to settle claims it funneled funds through a charity foundation to cover federal copays for patients taking its JAK inhibitor Jakafi, the DOJ said this week.

UP­DAT­ED: EMA safe­ty com­mit­tee seeks more in­fo on heart in­flam­ma­tion fol­low­ing Pfiz­er Covid-19 vac­cine

The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 104,800+ biopharma pros reading Endpoints daily — and it's free.