Sarep­ta’s eteplirsen spurned as Eu­ro­pean reg­u­la­tors turn thumbs down on con­tro­ver­sial Duchenne MD drug

Sarep­ta’s ap­proval for eteplirsen — or Ex­ondys51 — in the US re­mains one of the most con­tro­ver­sial OKs in FDA his­to­ry, earn­ing a rare la­bel that says the biotech has yet to pro­duce ev­i­dence the drug works.

But light­ning won’t strike twice on the reg­u­la­to­ry path­way for this biotech.

The biotech re­port­ed Thurs­day af­ter­noon that the CHMP is prep­ping a neg­a­tive vote, bar­ring the drug from the con­ti­nent. And Sarep­ta shares im­me­di­ate­ly tum­bled 5% in af­ter-mar­ket trad­ing.

Doug In­gram

The drug, which has a sol­id set of sup­port­ers in the DMD com­mu­ni­ty, is get­ting snubbed de­spite the Eu­ro­peans’ ac­cep­tance of PTC Ther­a­peu­tics’ ri­val drug, which has failed re­peat­ed piv­otal stud­ies. But in DMD, reg­u­la­tors have a ten­den­cy to make things up as they go along, fre­quent­ly bend­ing the rules to ac­com­mo­date a pas­sion­ate group of pa­tients and par­ents — or not. PTC has been re­peat­ed­ly slapped down by the FDA, even af­ter Janet Wood­cock over­ruled a host of agency in­sid­ers with her in­sis­tence on ap­prov­ing eteplirsen.

Sarep­ta CEO Doug In­gram had this to say:

Un­for­tu­nate­ly, the CHMP’s trend vote was neg­a­tive. Based on dis­cus­sions with CHMP rep­re­sen­ta­tives, it is our un­der­stand­ing that the CHMP did not con­clude that eteplirsen is in­ef­fec­tive for ex­on 51 amenable pa­tients, but rather that Sarep­ta has not yet met the reg­u­la­to­ry thresh­old for con­di­tion­al ap­proval, in part due to the use of ex­ter­nal con­trols as com­para­tors in the stud­ies. Sarep­ta plans to file for re-ex­am­i­na­tion and will re­quest that a Sci­en­tif­ic Ad­vi­so­ry Group (SAG), which is made up of DMD and neu­ro­mus­cu­lar spe­cial­ists, be con­vened to pro­vide ex­pert guid­ance and in­sight in­to, among oth­er things, the va­lid­i­ty of the ex­ter­nal con­trols used and the im­por­tance of slow­ing pul­monary de­cline in pa­tients with DMD.

Hop­ing to take some of the sting out of the news, while dis­ap­point­ing some an­a­lysts with its Q1 per­for­mance, Sarep­ta al­so an­nounced a deal to part­ner with My­onexus Ther­a­peu­tics on its work de­vel­op­ing gene ther­a­pies for Limb-gir­dle mus­cu­lar dy­s­tro­phies. Sarep­ta paid $60 mil­lion up­front and of­fered $45 mil­lion more in mile­stones for the deal, which al­so pro­vides the biotech with a buy­out op­tion at proof-of-con­cept.

“My­onexus and its fo­cus on gene ther­a­py us­ing the AAVrh.74 vec­tor to treat forms of LGMD aligns bril­liant­ly with our vi­sion to emerge as one of the most mean­ing­ful glob­al pre­ci­sion ge­net­ic med­i­cine com­pa­nies by fo­cus­ing on the use of ge­net­ic med­i­cine to im­prove the lives of those with rare fa­tal dis­eases,” said In­gram in a pre­pared state­ment.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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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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David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.

Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.

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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