PTC's ataluren flops in an­oth­er PhI­II and an an­a­lyst says it's clear­ly a dud; kill it

PTC Ther­a­peu­tics CEO Stu­art Peltz

PTC Ther­a­peu­tics has whiffed once again on Translar­na (ataluren).

The biotech re­port­ed that ataluren, a re­peat flop in Duchenne mus­cu­lar dy­s­tro­phy, failed a Phase III for non­sense mu­ta­tion cys­tic fi­bro­sis on both the pri­ma­ry and sec­ondary end­points.

In­ves­ti­ga­tors tracked a slight but in­signif­i­cant ad­van­tage for pa­tients in the drug arm of the  CF study, not­ing a bet­ter num­ber for lung ca­pac­i­ty and the rate of pul­monary ex­ac­er­ba­tions. But none of it stacked up in a way worth tak­ing to reg­u­la­tors, and the biotech says it will scrap its work in CF and jerk its ap­pli­ca­tion for ap­proval in Eu­rope.

The com­pa­ny’s stock $PTCT dropped 20% on the news.

PTC has a long track record of fail­ure in the clin­ic when it comes to ataluren. A flop in Phase IIb as well as Phase III for DMD, the FDA re­fused to ac­cept its ap­pli­ca­tion for re­view in ear­ly 2016, say­ing the biotech’s pitch failed to qual­i­fy for a re­view — a rare slap­down from reg­u­la­tors. PTC is now ap­peal­ing that de­ci­sion for the sec­ond time.

De­spite that, though, Eu­ro­pean of­fi­cials have al­lowed the sale of Translar­na for Duchenne mus­cu­lar dy­s­tro­phy. The Eu­ro­pean Com­mis­sion rat­i­fied an ex­ten­sion of PTC’s mar­ket­ing ap­proval in ear­ly Jan­u­ary as PTC pur­sues an­oth­er study to keep its mar­ket­ing au­tho­riza­tion in place. And the biotech ex­pects to earn more than $100 mil­lion this year on sales out­side the US, backed by a num­ber of pa­tient ad­vo­cates who be­lieve the drug works, de­spite the da­ta.

RBC’s Simos Sime­oni­dis said this af­ter­noon that the string of tri­al fail­ures demon­strate that the drug is clear­ly a dud and ought to be pulled.

Fol­low­ing this com­pound’s fail­ure in the ACT DMD tri­al, which was sup­posed to be the con­fir­ma­to­ry tri­al (which based on post-hoc analy­ses from a Phase II tri­al in DMD that had failed to meet its pri­ma­ry end­point), we no longer be­lieved this com­pound worked in CF, and had thus as­signed 0% prob­a­bil­i­ty of suc­cess for it in ACT CF. We now be­lieve there is am­ple clin­i­cal ev­i­dence from mul­ti­ple ran­dom­ized clin­i­cal tri­als that this is an in­ac­tive com­pound.

“We are dis­ap­point­ed with the out­come of this tri­al as there are no treat­ments that tar­get the un­der­ly­ing cause of non­sense mu­ta­tion cys­tic fi­bro­sis, one of the most dif­fi­cult forms to treat,” said Stu­art W. Peltz, PhD, chief ex­ec­u­tive of­fi­cer of PTC Ther­a­peu­tics in pre­pared text. “We are par­tic­u­lar­ly grate­ful to pa­tients and in­ves­ti­ga­tors who par­tic­i­pat­ed in our tri­als. We re­main com­mit­ted to pa­tients re­ceiv­ing ataluren in oth­er in­di­ca­tions.”

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.