NGM Bio un­veils pos­i­tive PhII NASH re­sults to some unim­pressed in­vestors

NGM Bio got up ear­ly this morn­ing in South San Fran­cis­co ready to pro­claim an in­ter­im win of its lead NASH drug, aldafer­min, in the fourth and fi­nal leg of a lengthy Phase II pro­gram. The re­sults of com­par­ing drug to place­bo were pos­i­tive, the com­pa­ny said, set­ting up some ex­pec­ta­tions for a fi­nal read­out in ear­ly 2020.

But in­vestors weren’t quite buy­ing it. The stock $NGM has slid around 18%.

So what’s wrong?

It may be help­ful to re­mem­ber, first of all, that NASH is a block­buster sized mar­ket that’s en­ticed mul­ti­ple biotech play­ers from In­ter­cept and Madri­gal to Gen­fit and Viking, and any signs of ear­ly hope or doom — es­pe­cial­ly as com­pared to oth­er ri­vals, de­spite the dan­gers of cross-tri­al com­par­isons — could cast dif­fer­ent lights on the da­ta.

David Wood­house

With that, here’s what NGM has re­port­ed about the 38-pa­tient tri­al: A 24-week treat­ment with once-dai­ly 1 mg aldafer­min, or NGM282, met the pri­ma­ry end­point re­gard­ing changes in ab­solute liv­er fat con­tent achiev­ing a drop of 7.9% ver­sus 2.0% on place­bo as mea­sured by MRI-es­ti­mat­ed pro­ton den­si­ty fat frac­tion (p<0.05).The change in rel­a­tive LFC came in at a dra­mat­ic -39.6% over -5.9% in the place­bo arm.

The com­pa­ny al­so not­ed that 72% of the aldafer­min group achieved 5% or more ab­solute re­duc­tion in LFC, com­pared to 17% of those tak­ing place­bo.

That’s in­deed pos­i­tive, and rough­ly in line with the Phase II da­ta Madri­gal pre­vi­ous­ly re­port­ed for their MGL-3196 (-36.3% rel­a­tive re­duc­tion on drug vs 9.6% on place­bo). But it fell short of the 57-60% me­di­an rel­a­tive change and 77-91% re­spon­der rate that Viking post­ed last year, spark­ing a surge in share price.

Hsiao Lieu

Some­thing else might al­so be dri­ving the con­cern: a spike in cho­les­terol lev­els (LDL-C to be spe­cif­ic) at week 2 of treat­ment. While NGM con­tends it’s noth­ing they didn’t know from pre­vi­ous Phase II co­horts, that it’s a di­rect ef­fect of FGF19’s in­hi­bi­tion of the clas­si­cal bile acid syn­the­sis path­way and that it was quick­ly re­solved by statin treat­ment, a mean in­crease of 47.6 mg/dL in LDL-C rel­a­tive to a 103.5 mg/dL base­line could be alarm­ing to a pa­tient pop­u­la­tion that al­ready has height­ened car­dio­vas­cu­lar risks.

CEO David Wood­house main­tained they are pleased with the in­ter­im find­ings, part of an ex­pan­sive clin­i­cal cam­paign fund­ed by a $200 mil­lion-plus part­ner­ship with Mer­ck and a $107 mil­lion IPO a few months ago.

“Aldafer­min con­tin­ues to be dif­fer­en­ti­at­ed with what we be­lieve is an in­dus­try-lead­ing pro­file as a monother­a­py for the po­ten­tial treat­ment of NASH, as few drugs in de­vel­op­ment for this dis­ease have shown mean­ing­ful meta­bol­ic, an­ti-in­flam­ma­to­ry and an­ti-fi­brot­ic ac­tiv­i­ty,” CMO Hsiao Lieu added in a state­ment. “Through­out our Phase 2 pro­gram, we’ve seen a re­la­tion­ship be­tween aldafer­min’s im­pact on bio­mark­ers of dis­ease and sub­se­quent his­tol­ogy re­sults. To that end, we look for­ward to the biop­sy da­ta read­out for Co­hort 4, which will fur­ther in­form plan­ning ac­tiv­i­ties for our Phase 3 study.”

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

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Vas Narasimhan. Getty Images

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

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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.
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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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David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

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Bhaskar Chaudhuri. Frazier Healthcare Partners

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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.

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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.