Un­fazed by fail­ure, PTC Ther­a­peu­tics to ap­peal neg­a­tive EMA de­ci­sion on its dis­as­ter prone Duchenne drug

PTC Ther­a­peu­tics’ bid to ex­pand the ap­proval of its Duchenne mus­cu­lar dy­s­tro­phy drug in Eu­rope has been un­suc­cess­ful. The New Jer­sey-based drug­mak­er is not known for tak­ing no for an an­swer and will ap­peal the de­ci­sion, it said on Fri­day.

The drug, ataluren, has a check­ered past, lit­tered with failed tri­als.

In Eu­rope, the drug — brand­ed as Translar­na — was con­di­tion­al­ly ap­proved by the EMA in 2014 to treat pa­tients aged 2 and old­er with DMD who are able to walk, just ahead of the read­out of a late-stage study, which showed the drug had failed.

The EMA has now re­fused to back the drug’s use in non-am­bu­la­to­ry pa­tients based on the fresh da­ta pro­vid­ed by PTC. The com­pa­ny pre­sent­ed da­ta from a study in­volv­ing 94 pa­tients with non­sense mu­ta­tion DMD — of which 44 were non-am­bu­la­to­ry. The study was pow­ered to as­sess the long-term safe­ty of Translar­na, but al­so in­ves­ti­gat­ed the ef­fec­tive­ness of the treat­ment in pa­tients un­able to walk, mea­sur­ing changes in lung func­tion, ver­sus his­tor­i­cal da­ta, the EMA said.

The EMA con­clud­ed the da­ta did not es­tab­lish the drug’s bal­ance of ben­e­fits and risks in non-am­bu­la­to­ry pa­tients. “The fact that Translar­na is han­dled by the body in a sim­i­lar way in pa­tients who can walk and those who can­not was not enough to con­firm the ef­fec­tive­ness of Translar­na in these pa­tients. This is be­cause pa­tients un­able to walk are at a more ad­vanced stage of the dis­ease and have re­duced mus­cle mass and there­fore the ben­e­fits of treat­ment may be dif­fer­ent. The ad­di­tion­al da­ta from the study could al­so not con­firm the ben­e­fit of Translar­na in pa­tients no longer able to walk be­cause there were prob­lems with the way da­ta from the CIN­RG (his­tor­i­cal da­ta) data­base, which was used to in­di­rect­ly com­pare the ef­fects of Translar­na, were se­lect­ed and analysed,” the EMA said.

PTC, on Fri­day, said it planned to re­quest a re-ex­am­i­na­tion in the com­ing weeks and ex­pects the re­view to last rough­ly 4 months. The com­pa­ny’s shares $PTCT slipped about 5% to $41 be­fore the bell.

Un­der the con­di­tion­al ap­proval, the EMA as­sess­es the drug’s ap­prov­abil­i­ty on an an­nu­al ba­sis. As ex­pec­ta­tions that the EMA would re­scind its back­ing grew af­ter the failed Phase III tri­al, PTC was giv­en a re­prieve in 2016 when the reg­u­la­tor al­lowed the com­pa­ny to keep the drug on the mar­ket if an ad­di­tion­al study con­firmed its ef­fect.

The study is de­signed to be a place­bo-con­trolled, 18-month tri­al, fol­lowed by an 18-month ex­ten­sion study — with da­ta was ex­pect­ed in 2021. But, in a fil­ing post­ed in March this year, PTC ac­knowl­edged the study is run­ning be­hind sched­ule, due to slow­er-than-ex­pect­ed en­roll­ment, and that it has asked the EMA for an ex­ten­sion. Mean­while, the com­pa­ny’s bid to con­vince the EMA to grant Translar­na full ap­proval, from con­di­tion­al ap­proval, has been de­nied.

In the Unit­ed States, PTC has had lit­tle luck. The FDA spurned the drug twice, and when com­pa­ny asked for a third re­view — em­bold­ened per­haps by Sarep­ta’s $SRPT DMD ap­proval of Ex­ondys 51, de­spite in­suf­fi­cient da­ta — the US health agency re­fused to even take a look at their ap­pli­ca­tion. Then, em­ploy­ing a reg­u­la­to­ry loop­hole in the FDA’s own laws, PTC filed its ap­pli­ca­tion “in protest” forc­ing the FDA to take yet an­oth­er look. The third time was not a charm. By the third try, the drug had al­so failed a study in cys­tic fi­bro­sis — giv­ing the FDA fur­ther im­pe­tus to is­sue its third, de­ci­sive re­jec­tion. In the fourth quar­ter of 2018, PTC ini­ti­at­ed a new tri­al in yet an­oth­er bid to change the FDA’s mind — and ex­pects to make its fourth NDA at­tempt next year.

PTC does, how­ev­er, have an­oth­er DMD drug on the US mar­ket. In 2017, the drug­mak­er shelled out $140 mil­lion to ac­quire a cheap, old steroid for DMD from Marathon Phar­ma­ceu­ti­cals — a com­pa­ny that had weath­ered a tem­pest of crit­i­cism for the $89,000 an­nu­al price it had slapped on the steroid, de­flaza­cort. Scores of par­ents had been im­port­ing the gener­ic from the UK for around $1,000 a year, but when Marathon got it ap­proved as an or­phan drug for DMD in the Unit­ed States, that door ef­fec­tive­ly closed. PTC in­her­it­ed the scan­dal when it bought the drug, and in its at­tempt to si­lence crit­ics, cut the price to $35,000 per year.

Late­ly, PTC has been work­ing on oth­er pro­grams. Its oral spinal mus­cu­lar at­ro­phy drug — ris­diplam — part­nered with Roche is ex­pect­ed to mount a chal­lenge to Bio­gen’s $BI­IB Spin­raza and No­var­tis’ $NVS gene ther­a­py Zol­gens­ma.

So­cial im­age: Shut­ter­stock

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Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

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Jeff Kindler's Cen­trex­ion re­news bid to make pub­lic de­but

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The Boston based company, led by former Pfizer $PFE chief Kindler, originally contemplated a $70 million to $80 million IPO last year— but eventually postponed that strategy. On Wednesday, the company revived its bid to make a public debut in a filing with the SEC — although no pricing details were disclosed.

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'A fourth rev­o­lu­tion in can­cer ther­a­pies': ARCH-backed Bound­less Bio flash­es big check, makes big­ger promis­es in de­but

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