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.”

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”

Pfiz­er ax­es 6 ear­ly to late-stage can­cer stud­ies from the pipeline — with one oth­er cut for sick­le cell dis­ease

Pfizer trimmed a group of 3 R&D programs using their PD-L1 Bavencio — partnered with Merck KGaA — in their latest pipeline cull.

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UP­DAT­ED: In­cyte scores much need­ed PhI­II suc­cess — and of course it’s de­liv­ered by rux­oli­tinib

Incyte’s efforts to breathe a second life into ruxolitinib — its JAK inhibitor sold in pill form as Jakafi — has been greeted with clear, if preliminary and unsurprising, Phase III success.

Topline data from the TRuE-AD2 cements ruxolitinib’s foundational importance for Incyte, and gives analysts hope that there might yet be room for growth in a pipeline that’s suffered multiple R&D setbacks.

Stephen Hahn, AP

The FDA un­veils a new reg­u­la­to­ry frame­work to speed along gene ther­a­pies, re­ward­ing the lead­ing play­ers

Bioregnum Opinion Column by John Carroll

The emphasis at the FDA over the past 5 years or so has been on assisting drug developers as much as they can to speed up regulatory reviews and push more drugs into the market. And they are now crafting a final set of regulations aimed at flagging through a whole new generation of gene therapies in clinical testing at a rapid clip.

In a set of 6 prospective guidances posted on the FDA web site Tuesday morning, FDA commissioner Stephen Hahn committed the agency to staying flexible in handing out designations that are critical to gaining early approvals for drugs that claim to be once-and-done but don’t have anything close to the data needed to prove it.

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Mike Bloomberg (AP IMAGES)

Mike Bloomberg joins a grow­ing cho­rus of De­mo­c­ra­t­ic pres­i­den­tial can­di­dates threat­en­ing to go af­ter drug patents

As the mayor of New York City, Mike Bloomberg had a few modest ideas about lowering prescription drug prices in the Big Apple that gained little traction. Now on the campaign trail on a faint hope of clinching the Democratic presidential nomination, the billionaire has some bigger plans — including one that would alter the patent system central to the biopharma business.

In a barebones drug pricing plan posted on Monday, Bloomberg came out blasting President Donald Trump for failing to deliver his promise to lower drug prices, and then making misleading claims about them. The price of over 3,000 drugs still increased at a rate five times higher than inflation in the first six months of 2019, he wrote.