#AACR18 round 1: Mer­ck takes a di­rect swing at Bris­tol-My­ers with ad­ju­vant melanoma da­ta for Keytru­da

CHICA­GO — Mer­ck $MRK came out of its cor­ner swing­ing Sun­day morn­ing, tak­ing a few di­rect jabs at the de­fend­ing cham­pi­on in check­point in­hi­bi­tion as the phar­ma gi­ant en­tered the lat­est I/O ti­tle fight with Bris­tol-My­ers Squibb $BMY at the an­nu­al meet­ing of AACR in Chica­go.

Roger Perl­mut­ter, Mer­ck

Re­searchers for Mer­ck were in Chica­go for the cur­tain open­er in what promis­es to be a bruis­ing brawl be­tween the lead­ers in the PD-1 field over a mar­ket one an­a­lyst has said is worth $3 bil­lion.

In KEYNOTE-054, Mer­ck de­ter­mined that 18 dos­es of Keytru­da pushed post-surgery pa­tients with stage 3 melanoma to a re­cur­rence-free rate of 75.4% com­pared to 61% for a com­par­i­son group get­ting a place­bo. A 43% drop in re­cur­rence rate was some­thing Mer­ck tout­ed as a ma­jor ad­vance for pa­tients.

Mer­ck is look­ing to carve away mar­ket share from Bris­tol-My­ers any way it can. And they’ll have their work cut out in Stage 3 melanoma. Bris­tol-My­ers won an ap­proval to use Yer­voy in this group three years ago, and fol­lowed up with an OK for Op­di­vo last year, mak­ing them the go-to play­er for ad­ju­vant ther­a­py.

Mer­ck, though, didn’t hes­i­tate to make its case in their out­line of the re­sults Sun­day morn­ing. Yer­voy, they note, is no­to­ri­ous­ly tox­ic for pa­tients, who may well pre­fer an al­ter­na­tive. And Op­di­vo? They have an ar­gu­ment there as well.

“Nivolum­ab was more ef­fec­tive and had few­er side ef­fects than ip­il­i­mum­ab, but it is giv­en at a dose of 3 mil­ligrams per kilo­gram every two weeks for up to a year, which is 26 dos­es in to­tal,” not­ed Alexan­der Eg­ger­ment, di­rec­tor gen­er­al of Gus­tave Roussy Can­cer Cam­pus Grand Paris, mak­ing Mer­ck’s case. “Pem­brolizum­ab may prove con­ve­nient to pa­tients and hos­pi­tals be­cause it re­quires few­er out­pa­tient hos­pi­tal vis­its and is giv­en at a flat dose.”

Mer­ck is hunt­ing ap­provals in the US and Eu­rope so they can take that pitch di­rect­ly to physi­cians.

A spokesper­son for Bris­tol-My­ers, though, fol­lowed up with me to note that “the ad­ju­vant melanoma dos­ing for nivolum­ab was up­dat­ed with the Q4W ap­proval and is now ap­proved for flat dos­ing 240 mg every two weeks or 480 mg every four weeks.”

Bris­tol-My­ers won an FDA ap­proval af­ter Check­mate-238 demon­strat­ed that Op­di­vo was bet­ter than Yer­voy in hold­ing back melanoma for post-surgery stage 3 and 4 pa­tients. In that study, the re­cur­rence rate for Op­di­vo at a me­di­an fol­low-up of 18.5 months was 66.4% for Op­di­vo and 52.7% for Yer­voy.

Whats at stake? Ac­cord­ing to Sea­mus Fer­nan­dez at Leerink, about $3 bil­lion. Here’s his com­ment on the -238 re­sults from last sum­mer:

We es­ti­mate the ad­ju­vant melanoma mar­ket will ex­pand PD1 sales by ap­prox­i­mate­ly $3B glob­al­ly. Al­though this like­ly will can­ni­bal­ize sales of Yer­voy in the set­ting (we es­ti­mate cur­rent ad­ju­vant Yer­voy sales at $300-400M), the ex­pan­sion of the mar­ket should add ap­prox­i­mate­ly $1B to BMY’s net im­muno-on­col­o­gy (IO) sales de­spite as­sumed com­pe­ti­tion from MRK’s (MP) Keytru­da (pem­brolizum­ab; an­ti-PD-1).

It’s not just about mon­ey, though. Ever since Bris­tol-My­ers rolled out in front of Mer­ck, Roger Perl­mut­ter’s team has been fo­cused on claim­ing the lead. A key mis­step on lung can­cer at Bris­tol-My­ers gave them an ad­van­tage they’ve been ex­ploit­ing ever since — which we’ll al­so hear more about over the next two days.

This par­tic­u­lar show­down has just be­gun.

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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