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

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.