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.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA commissioner Stephen Hahn at the White House (AP Images)

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Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

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Vas Narasimhan (AP Images)

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Isaac Veinbergs, Libra CEO

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Patrick Enright, Longitude co-founder (Longitude)

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Gene Wang, Immetas co-founder and CEO (file photo)

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Samit Hirawat (Bristol Myers Squibb)

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