Dean Hum. Nasdaq via YouTube

Gen­fit goes to Chi­na with a deal worth up to $228M for NASH drug

Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes weeks af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.

The two treat­ments be­long to a fam­i­ly of drugs that ac­ti­vate pro­teins called per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tors (PPARs), which reg­u­late gene ex­pres­sion. Ex­ist­ing ev­i­dence sug­gests that in the liv­er, PPAR ag­o­nists play a role in bile acid syn­the­sis, in­flam­ma­tion, fi­bro­sis and lipid me­tab­o­lism.

NASH is an un­treat­ed fat­ty liv­er dis­ease that has rav­aged the de­vel­oped world, cre­at­ing a lu­cra­tive tar­get that has sparked a flur­ry of drug de­vel­op­ment from bio­phar­ma firms big and small. It is char­ac­ter­ized by a buildup of ex­cess fat in the liv­er that in­duces chron­ic in­flam­ma­tion and even­tu­al­ly cul­mi­nates in scar­ring that can lead to cir­rho­sis, liv­er fail­ure, can­cer and death.

Pas­cal Pri­gen LinkedIn

Dubbed the silent dis­ease, it is hard to di­ag­nose in the ear­ly stages, mak­ing it dif­fi­cult to es­ti­mate its preva­lence, but stud­ies show that it af­flicts up to 12% of the adult pop­u­la­tion in de­vel­oped coun­tries. Al­though there are no ap­proved drugs for the dis­ease, the size of the NASH mar­ket is ex­pect­ed to cross $20 bil­lion by 2025.

While oth­er ma­jor NASH con­tenders — Gilead $GILD (fail in Phase III) and In­ter­cept $ICPT (mixed win in Phase III) — have dis­closed the top-line num­bers of their late-stage tri­als, Gen­fit is ex­pect­ed to come out with its Phase III in­ter­im re­sults by the end of 2019, or ear­ly 2020.

Late-stage da­ta on In­ter­cept’s drug — obeti­cholic acid (OCA) — showed it in­duced a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in fi­bro­sis, but not NASH res­o­lu­tion, and a high­er-than-ex­pect­ed num­ber of pa­tients dropped out due to the pesky side-ef­fect of itch­ing. In con­trast to In­ter­cept, Gen­fit has em­pha­sized that elafi­bra­nor’s po­ten­tial in NASH res­o­lu­tion and re­duc­ing CV risk along with a be­nign safe­ty and tol­er­a­bil­i­ty pro­file have set it apart.

“We think we’re go­ing to be the first drug on the mar­ket that can re­solve NASH,” Gen­fit’s COO Dean Hum stressed in an in­ter­view with End­points News.

He sug­gest­ed that Cymabay had “made a mis­take” to fo­cus on liv­er fat, when they should have con­cen­trat­ed on in­flam­ma­tion and fi­bro­sis — the fac­tors that con­sti­tute NASH res­o­lu­tion.

But some an­a­lysts are not quite as con­vinced.

In the af­ter­math of the Cymabay da­ta, Baird’s Bri­an Sko­r­ney sug­gest­ed se­ladel­par and elafi­bra­nor are be­gin­ning to ap­pear more sim­i­lar than dif­fer­ent.

“Though the two med­ica­tions were thought to have dif­fer­en­ti­at­ed mech­a­nisms of ac­tion, it seems that this may not be the case, as se­ladel­par’s da­ta sug­gest that the med­ica­tion does not re­duce liv­er fat, which is sim­i­lar to what we have seen from ear­li­er tri­als of elafi­bra­nor. This leads us to be­lieve that these two PPARs look much more sim­i­lar than dif­fer­ent. Hence, CymaBay may be at a sig­nif­i­cant dis­ad­van­tage mov­ing for­ward as we be­lieve that even if PPAR ag­o­nism is suc­cess­ful in Gen­fit‘s Phase 3 tri­al, with­out any clear signs of dif­fer­en­ti­a­tion, CymaBay may have an up­hill bat­tle as they work to catch up to Gen­fit in NASH. If elafi­bra­nor fails in NASH, it would prob­a­bly be pre­dic­tive of the out­come of se­ladel­par in NASH. Ei­ther way, we think this makes the PPAR class, as a whole, look like a less sig­nif­i­cant com­pet­i­tive threat to OCA.”

While the bulk of obe­si­ty and re­lat­ed dis­eases have tra­di­tion­al­ly been the wheel­house of the West­ern world, rapid ur­ban­iza­tion in parts of Asia has nor­mal­ized seden­tary lifestyles and over­nu­tri­tion, set­ting the stage for obe­si­ty in epi­dem­ic pro­por­tions. A study pub­lished in 2017 sug­gests the in­ci­dence of obe­si­ty has been in­creas­ing at an alarm­ing rate, par­tic­u­lar­ly in Chi­na, Japan and In­dia. “The num­ber of obese Chi­nese peo­ple was be­low 0.1 mil­lion in 1975, ris­ing to 43.2 mil­lion in 2014 and ac­count­ing for 16.3% of glob­al obe­si­ty,” re­searchers found.

Gen­fit’s new part­ner Terns is well versed in NASH. Last year, it joined forces with Eli Lil­ly to de­vel­op the US drug­mak­er’s ear­ly-stage NASH as­sets, in ad­di­tion to its own.

Un­der the deal, Terns — which has op­er­a­tions in Cal­i­for­nia, as well as a set­up in Chi­na — will hand over $35 mil­lion up­front, in ad­di­tion to up to $193 mil­lion in po­ten­tial mile­stone pay­ments to de­vel­op Gen­fit’s late-stage as­set elafi­bra­nor for use in NASH and pri­ma­ry bil­iary cholan­gi­tis (PBC).

A key rea­son be­hind the deal was that since elafi­bra­nor’s ex­ist­ing late-stage study does not in­clude Chi­nese pa­tients, an­oth­er Phase III study in­clud­ing such pa­tients would be re­quired for Chi­nese ap­proval, Pas­cal Pri­gent, Gen­fit’s ex­ec­u­tive VP of mar­ket­ing and com­mer­cial de­vel­op­ment, told End­points News.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

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The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

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Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

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So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Moderna, the first US company to put their vaccine into human testing, was supposed to enter a 30,000-person study this month in partnership with the NIH to determine whether it can prevent infection. STAT reported last week that the trial was facing delays over the protocol, but that a July start was still possible. Neither the NIH nor Moderna ever disclosed a specific date the trial should start, but Reuters reported that the agency had hoped to begin on July 10.

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The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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