Gilead needs a big R&D hit. Here's why claims on NASH fall well short of that

For months now, the pres­sure has been build­ing on Gilead to do some­thing dra­mat­ic on the R&D side of the busi­ness, with an­a­lysts clam­or­ing for the big biotech to buy some­thing or build some­thing big.

Bri­an Sko­r­ney, Baird an­a­lyst

So when re­searchers claimed that they had hit pay dirt da­ta in a mid-stage study of GS-4997 for a block­buster in­di­ca­tion like NASH, the com­pa­ny built it up as en­cour­ag­ing proof of ef­fi­ca­cy and sig­nif­i­cant progress on an im­por­tant front.

A big Phase III now comes next, says Gilead, adding an­oth­er high-pro­file late-stage ef­fort with po­ten­tial block­buster out­comes. It’s stock is up 1.4%.

But Gilead is ex­pe­ri­enc­ing a sharp back­lash on this one.

“We be­lieve this study an­swers noth­ing about the drug’s prob­a­bil­i­ty of hav­ing an ef­fect as we be­lieve NASH study de­sign lim­i­ta­tions make the ef­fi­ca­cy re­sults un­in­ter­pretable,” not­ed Baird’s Bri­an Sko­r­ney.

Let’s look at what Gilead put out to­day.

A to­tal of 72 NASH pa­tients with mod­er­ate to se­vere fi­bro­sis were giv­en ei­ther 18 mg or 6 mg of the oral drug per day, ei­ther alone or in com­bi­na­tion with sim­tuzum­ab – an­oth­er one of Gilead’s ex­per­i­men­tal drugs – with one arm re­served for sim­tuzum­ab alone. And the 67 evalu­able pa­tients per­formed well af­ter 24 weeks. The high dose com­bi­na­tion de­liv­ered a 43% rate for an im­prove­ment on fi­bro­sis, the low dose 30% and the con­trol arm hit 20%. The pro­gres­sion to cir­rho­sis was 3% in the high dose, 7% in the low dose and 20% in the sim­tuzum­ab-alone arm.

That’s a short pe­ri­od for these pa­tients with the fat­ty liv­er dis­ease. And it’s not many pa­tients. So what’s the da­ta worth?

Not a lot for some.

“If all you look at is the point es­ti­mate across the three arms, it looks like a home run,” says Sko­r­ney. “How­ev­er, we be­lieve the char­ac­ter­is­tics of the dis­ease and tri­al de­sign makes this an un­in­ter­pretable study, from an ef­fi­ca­cy per­spec­tive. The er­ror bars are huge and siz­able place­bo ef­fects are well doc­u­ment­ed. Com­par­ing to­day’s press re­lease with the da­ta in the AASLD late-break­ing ab­stract (Fig­ure 1), the ad­di­tion of 20 pa­tients marked­ly de­creased sep­a­ra­tion be­tween groups. In these 20 ad­di­tion­al pa­tients, the re­sponse went the op­po­site di­rec­tion, with 50% of pa­tients not get­ting GS-4997 show­ing a fi­brot­ic im­prove­ment vs. 25% on the low dose and 20% on the high dose. We on­ly high­light this to say, don’t read any­thing in­to the ef­fi­ca­cy re­sults of this study. The num­bers are too small, the du­ra­tion of treat­ment is too short and the da­ta is com­pli­cat­ed by the in­clu­sion of an­oth­er drug in­stead of place­bo.”

Gilead CSO Nor­bert Bischof­berg­er

Fur­ther dim­ming ex­pec­ta­tions are two failed mid-stage stud­ies. Gilead says the same drug failed on pul­monary ar­te­r­i­al hy­per­ten­sion (PAH) and di­a­bet­ic kid­ney dis­ease (DKD), so those pro­grams are be­ing scrapped.

Head­ing straight in­to Phase III with GS-4997, though, prob­a­bly makes more sense than try­ing to ex­e­cute a big Phase II to see if the da­ta stand up, adds the an­a­lyst.

Gilead’s share price has been steadi­ly dwin­dling for months as its tor­rent of hep C cash has slowed. An­a­lysts want to see some­thing that can fire up the rev­enue ma­chine again, but as of to­day, they’re still not get­ting it.

Gilead CSO Nor­bert Bischof­berg­er had this to say:

“We are en­cour­aged by these da­ta demon­strat­ing the an­ti-fi­brot­ic ef­fect of GS-4997 in pa­tients with NASH af­ter on­ly 24 weeks of treat­ment, and look for­ward to shar­ing the com­plete re­sults with the he­pa­tol­ogy com­mu­ni­ty. Ad­di­tion­al­ly, pend­ing dis­cus­sions with reg­u­la­to­ry agen­cies, we plan to ini­ti­ate a Phase 3 clin­i­cal tri­al pro­gram of GS-4997 in pa­tients with NASH.”

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

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Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

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Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

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As­traZeneca gains EU nod for di­a­betes triple; Am­gen and Duke launch re­al-world PC­SK9 ob­ser­va­tion­al study

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Five drugs, in­clud­ing two No­var­tis ther­a­pies, win EMA en­dorse­ment

As is custom, an EMA panel on Friday issued its weekly recommendations on marketing applications submitted by drug developers. This week, the agency backed the use of five new therapies — including two Novartis drugs — but issued no negative reviews.

Novartis’ S1P drug for relapsing forms of multiple sclerosis (MS) drug, Mayzent (known chemically as siponimod), which was approved by the FDA in March — has been given the nod by the EMA. The Swiss drugmaker already sells its other MS drug, Gilenya, in both regions.

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→ After snapping up Novartis’ Swiss facility, Novartis Center of Excellence, in July, Lonza has announced that their CEO, Marc Funk, is hitting the exit for “personal reasons.” Funk has been the CEO of the company for less than a year — brought onto the company back in March. In the meantime, chairman Albert Baehny will serve as interim CEO. 

BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: In a first, FDA green-lights use of a Chi­nese built can­cer ther­a­py — and more are com­ing

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

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