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.

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

After attacks from activist investors and disappointing returns on share prices, Radius Health has now agreed to new ownership, a direction resulting in leaving the Nasdaq.

Radius Health, a biotech out of Massachusetts with one approved product in its arsenal, announced Thursday morning that it agreed to be acquired by two VC firms: Gurnet Point Capital and Patient Square Capital. The deal, worth around $890 million, will include debt assumption and the payout of $1 CVR per share for investors. And on top of that, OrbiMed is providing debt financing.

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”