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

Fangliang Zhang, AP Images

Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.