In the bat­tle against kid­ney can­cer, Mer­ck­'s key­stone im­munother­a­py Keytru­da edges in front

Mer­ck $MRK may not just have a leg up over Bris­tol-My­ers Squibb $BMY in the lu­cra­tive field of lung can­cer. It looks like the com­pa­ny’s block­buster check­point in­hibitor Keytru­da — large­ly con­sid­ered the pre­em­i­nent im­munother­a­py — is on its way to es­tab­lish­ing its edge in re­nal can­cer. Ahead of the Gen­i­touri­nary (GU) Can­cers Sym­po­sium lat­er this week, an ab­stract de­tail­ing the re­sults of a piv­otal study test­ing a Keytru­da com­bi­na­tion in pre­vi­ous­ly un­treat­ed re­nal cell car­ci­no­ma (RCC) pa­tients ce­ment­ed the PD-1 drug’s lead­ing sta­tus.

Topline da­ta re­leased last Oc­to­ber showed a com­bi­na­tion of Keytru­da and Pfiz­er’s $PFE ty­ro­sine ki­nase in­hibitor (TKI) In­ly­ta in the KEYNOTE-426 tri­al im­proved over­all sur­vival, pro­gres­sion-free sur­vival and over­all re­sponse rates across risk groups and re­gard­less of PD-L1 sta­tus, com­pared to Pfiz­er’s Su­tent, in first-line RCC pa­tients. Mer­ck of­fered fur­ther de­tail on Mon­day, in­di­cat­ing the Keytru­da com­bo sig­nif­i­cant­ly im­proved OS, re­duc­ing the risk of death by near­ly half (HR 0.53), as well as PFS (HR 0.69).

An­a­lysts cheered the da­ta. Cowen an­a­lysts sug­gest­ed that a TKI/IO com­bo will emerge as the stan­dard of care in first line RCC, and that they an­tic­i­pate sim­i­lar re­sults to emerge from the on­go­ing Check­Mate 9ER tri­al, which is test­ing a com­bi­na­tion of Op­di­vo and Ex­elix­is’ $EX­EL TKI Cabome­tyx ver­sus Su­tent in RCC pa­tients.

Keytru­da+In­ly­ta showed im­pres­sive over­all re­sults and will like­ly gain ap­proval in 1L set­ting. While these da­ta may cause some volatil­i­ty in EX­EL stock…the on­go­ing Check­Mate 9ER tri­al should re­port sim­i­lar if not bet­ter re­sults…Cabo re­mains the pre­ferred TKI for RCC based on NC­CN guide­lines. Ad­di­tion­al­ly, we an­tic­i­pate that many physi­cians will view KEYNOTE-426 as a class ef­fect (strong syn­er­gy be­tween TKI and check­point in­hibitor), and this may even re­sult in an in­cre­men­tal in­crease in cabo use in the front­line set­ting with a check­point in­hibitor pri­or to Check­Mate 9ER re­sults and po­ten­tial la­bel ex­pan­sion.

Cred­it Su­isse’s Vi­mal Di­van said the Keytru­da com­bo’s OS haz­ard ra­tio sur­passed ex­pec­ta­tions, con­sid­er­ing in­vestors had an­tic­i­pat­ed a HR around the 0.60 thresh­old.

“Bris­tol-My­ers has been gain­ing share in the 1L RCC mar­ket with their Op­di­vo + Yer­voy com­bo but Mer­ck’s da­ta ap­pears su­pe­ri­or giv­en a low­er OS HR, a pos­i­tive im­pact on PFS and an im­pact be­ing seen across a broad­er pop­u­la­tion. Op­di­vo + Yer­voy showed an OS ben­e­fit (but not a PFS ben­e­fit) over Su­tent in the Check­Mate-214 tri­al but on­ly in in­ter­me­di­ate and high-risk pa­tients and the ben­e­fit, in our view, be­ing dri­ven by the re­spons­es seen in pa­tients that were PD-L1 pos­i­tive. Over time, the avail­abil­i­ty of a gener­ic ver­sion of In­ly­ta (we as­sume in 2025) could al­so pro­vide a cost ad­van­tage for the Keytru­da + In­ly­ta reg­i­men over Op­di­vo + Yer­voy,” Di­van said.

In its fourth-quar­ter earn­ings call, Mer­ck said it has al­ready sub­mit­ted an ap­pli­ca­tion to mar­ket Keytru­da to treat first line RCC pa­tients, but Pfiz­er and Mer­ck KGaA on Mon­day said the FDA had agreed to a speedy re­view for their ap­pli­ca­tion to mar­ket a com­bi­na­tion of their check­point in­hibitor Baven­cio and In­ly­ta in RCC pa­tients — the agency is ex­pect­ed to make its de­ci­sion by June.

“(The) Baven­cio com­bi­na­tion with In­ly­ta may get to mar­ket in the US first, hav­ing been grant­ed pri­or­i­ty re­view by the FDA…based on da­ta from JAVELIN Re­nal 101. How­ev­er, we view Keytru­da + In­ly­ta as like­ly to over­take Baven­cio + In­ly­ta as well giv­en greater physi­cian com­fort with Keytru­da over Baven­cio and the pos­i­tive OS da­ta that KEYNOTE-426 de­liv­ered at the first in­ter­im analy­sis (as com­pared to JAVELIN Re­nal 101 where we on­ly saw a PFS ben­e­fit at the in­ter­im analy­sis),” Di­van added.

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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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.

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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