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.

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

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.

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.

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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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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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.