In a damn­ing in­dict­ment, FDA re­view scorns PTC’s Duchenne drug for re­peat­ed fail­ures

PTC Ther­a­peu­tics $PTCT ex­ec team proved this week that they are glut­tons for pun­ish­ment.

PTC Ther­a­peu­tics CEO Stu­art Peltz

Af­ter en­dur­ing two hu­mil­i­at­ing slap-downs at the FDA for their would-be Duchenne drug ataluren, the biotech — led by CEO Stu­art Peltz — has forced the agency’s hand, re­quir­ing a pan­el re­view on Thurs­day. And in the agency’s re­view of the drug, re­leased Tues­day morn­ing, the FDA went to con­sid­er­able lengths to ex­plain why they think this drug — pro­vid­ed an ac­cel­er­at­ed ap­proval in Eu­rope, where it’s sold to pa­tients as Translar­na — has re­peat­ed­ly proved to be un­wor­thy of an ap­proval.

PTC shares slid 23% af­ter the re­view land­ed, prov­ing that there are still clear lines on ef­fi­ca­cy that the FDA will not cross.

The sum­ma­ry says it all. Reg­u­la­tors at the FDA re­it­er­at­ed a se­ries of damn­ing con­clu­sions, with no pos­i­tive da­ta to con­sid­er. PTC’s post hoc analy­ses of failed stud­ies, they con­clud­ed, are un­con­vinc­ing in light of the fact that the re­sults were “clear­ly neg­a­tive”, while high­light­ing the “mis­lead­ing na­ture of ex­plorato­ry analy­ses of neg­a­tive tri­als.” And there’s no rea­son to be­lieve that any fu­ture tri­als of this drug will prove it can be ef­fec­tive.

In full, the FDA stat­ed:

Ul­ti­mate­ly, no pos­i­tive re­sults from any prospec­tive­ly planned analy­ses that are per­sua­sive have been pro­vid­ed with this ap­pli­ca­tion. The ap­pli­cant has pre­sent­ed on­ly the re­sults from nu­mer­ous post hoc and ex­plorato­ry analy­ses that are in­tend­ed to mit­i­gate two neg­a­tive clin­i­cal tri­als. In 2011, the ap­pli­cant claimed that the ef­fec­tive­ness of ataluren had been es­tab­lished based on the post hoc analy­ses of the ADP pop­u­la­tion in Study 007. How­ev­er, when this con­clu­sion was prospec­tive­ly eval­u­at­ed in Study 020, the re­sults were clear­ly neg­a­tive. This find­ing di­rect­ly high­lights the fre­quent­ly mis­lead­ing na­ture of ex­plorato­ry analy­ses of neg­a­tive tri­als. It is ar­guable that some trends ob­served in the ap­pli­cant’s da­ta may war­rant fur­ther prospec­tive in­ves­ti­ga­tion, which the Agency has con­sis­tent­ly en­cour­aged the ap­pli­cant to con­sid­er. Even so, for the rea­sons dis­cussed above, it seems quite pos­si­ble that any fu­ture study de­signed based on ex­plorato­ry analy­ses of Study 020 will al­so turn out to be neg­a­tive, just as Study 020, which was based on ex­plorato­ry post hoc analy­ses from Study 007, was neg­a­tive. The anal­o­gous re­sults from the ap­pli­cant’s de­vel­op­ment of ataluren for the treat­ment of nm­CF of­fer a sim­i­lar cau­tion­ary tale. Over­all, the da­ta in­tend­ed by the ap­pli­cant to es­tab­lish the ef­fec­tive­ness of ataluren for the treat­ment of nmD­MD are not per­sua­sive.

That qual­i­fies as one of the most con­clu­sive re­jec­tions I’ve seen of any drug ap­pli­ca­tion at the FDA. Pos­si­bly PTC was em­bold­ened by the agency’s ac­cel­er­at­ed OK of Sarep­ta’s drug, even though the com­pa­ny nev­er pro­vid­ed da­ta that the drug could work. In this case, though, the agency feels they have plen­ty of da­ta to con­clude that ataluren doesn’t work. And there’s no ev­i­dence to sug­gest that Janet Wood­cock will be rid­ing to PTC’s de­fense. Even a big show­ing of sup­port from Duchenne par­ents Thurs­day may prove un­like­ly to tip the scales in PTC’s fa­vor.

PTC, though, con­tin­ues to push ahead in DMD, re­gard­less of the crit­i­cism that has been lev­eled against it. That was proved again af­ter the com­pa­ny bought out  a cheap, old Eu­ro­pean steroid — de­flaza­cort — from Marathon Phar­ma­ceu­ti­cals af­ter Marathon ex­ecs de­cid­ed to bag it and flee from the in­tense re­ac­tion to their plans to price it at $89,000 list af­ter gain­ing the agency’s OK. PTC is now sell­ing de­flaza­cort at an even high­er rate for some of the old­er, larg­er boys suf­fer­ing from DMD af­ter par­ents had been able to source it abroad for about $1,000 a year.

Eu­ro­pean reg­u­la­tors have re­peat­ed­ly giv­en PTC a pass with their drug. And there’s no in­di­ca­tion that even a damn­ing re­sponse like this will change their po­si­tion.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.

Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.


Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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In a boost to Rit­ux­an fran­chise, Roche nabs quick ap­proval for po­latuzum­ab ve­dotin

Roche’s lat­est an­ti­body-drug con­ju­gate has crossed the FDA fin­ish line, gain­ing an ac­cel­er­at­ed ap­proval a full two months ahead of sched­ule.

Po­livy, or po­latuzum­ab ve­dotin, is a first-in-class drug tar­get­ing CD79b — a pro­tein promi­nent in B-cell non-Hodgkin lym­phoma. It will now be mar­ket­ed for dif­fuse large B-cell lym­phoma as part of a reg­i­men that al­so in­cludes the chemother­a­py ben­damus­tine and a ver­sion of rit­ux­imab (Rit­ux­an).

J&J gains an en­thu­si­as­tic en­dorse­ment from Pres­i­dent Don­ald Trump for their big new drug Spra­va­to

Pres­i­dent Don­ald Trump has lit­tle love for Big Phar­ma, but there’s at least one new drug that just hit the mar­ket which he is en­am­ored with.

Trump, ev­i­dent­ly, has been read­ing up on J&J’s new an­ti-de­pres­sion drug, Spra­va­to. And the pres­i­dent — who of­ten likes to break out in­to a full-throat­ed at­tack on greedy drug­mak­ers — ap­par­ent­ly en­thused about the ther­a­py in a meet­ing with of­fi­cials of Vet­er­ans Af­fairs, which has long grap­pled with de­pres­sion among vet­er­ans.

An in­censed Cat­a­lyst Phar­ma sues the FDA, ac­cus­ing agency of bow­ing to po­lit­i­cal pres­sure and break­ing fed­er­al law

Af­ter hint­ing it was ex­plor­ing the le­gal­i­ty of the FDA’s ap­proval of a ri­val drug from fam­i­ly-run com­pa­ny Ja­cobus Phar­ma­ceu­ti­cals, Cat­a­lyst Phar­ma­ceu­ti­cals on Wednes­day filed a law­suit against the health reg­u­la­tor — ef­fec­tive­ly ac­cus­ing the agency of bow­ing to po­lit­i­cal pres­sure sur­round­ing sky­rock­et­ing drug prices.

Be­fore Cat­a­lyst’s Fir­dapse (which car­ries an av­er­age an­nu­al list price of $375,000) was sanc­tioned for use in Lam­bert-Eaton myas­thenic syn­drome (LEMS) by the FDA, hun­dreds of pa­tients had been able to ac­cess a sim­i­lar drug from com­pound­ing phar­ma­cies for a frac­tion of the cost, or Ja­cobus’ for free, as part of an FDA-rat­i­fied com­pas­sion­ate use pro­gram. But the ap­proval of the Cat­a­lyst drug — ac­com­pa­nied by mar­ket ex­clu­siv­i­ty span­ning sev­en years — ef­fec­tive­ly pre­clud­ed Ja­cobus and com­pound­ing phar­ma­cies from sell­ing their ver­sions.

Plagued by de­lays, As­traZeneca HQ costs soar to £750M as it edges to­ward 2020 com­ple­tion

In the lat­est up­date on As­traZeneca’s de­lay-prone HQ project, the phar­ma gi­ant re­vealed that the cost of con­struc­tion has swelled to £750 mil­lion ($956 mil­lion) — more than dou­ble the orig­i­nal es­ti­mate in 2013.

The move-in date is still in 2020, a spokesper­son con­firmed, af­ter As­traZeneca pushed pro­ject­ed com­ple­tion from 2016 to 2017, and then to the spring of 2019. While the ini­tial plan called for a £330 mil­lion (then $500 mil­lion) in­vest­ment, the cost bal­looned to £500 mil­lion ($650 mil­lion), and more in the most re­cent up­date.