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.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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J&J ad­comm live blog: J&J work­ing on vac­cine for vari­ants, tri­al sched­uled for sum­mer

This week, Moderna announced it would begin testing a modified version of their mRNA vaccine to tackle the vaccine-resistant B1.351 variant that popped up in South Africa. Pfizer said it would test giving people an extra boost of its original vaccine to accomplish the same.

J&J revealed at the adcomm that they, too, have been working on a modified vaccine to tackle emerging variants.

The company didn’t reveal much detail, including how they modified the vaccine or if they were targeting the same B 1.351 variant, but Johan van Hoof said they would begin testing a new construct in the summer. The FDA has said they would allow modified vaccines for variants to be authorized after quick immunological studies that track whether the vaccine elicits antibodies against the new variant.