In the wake of deep R&D cuts, Bay­er flags safe­ty con­cerns for a top PhI­II drug

Less than a week af­ter Bay­er an­nounced plans to carve down its in­ter­nal R&D group, lay­ing off 900 R&D staffers, the Ger­man com­pa­ny has tipped the mar­ket that one of its cru­cial late-stage de­vel­op­ment ef­forts has run in­to se­ri­ous trou­ble.

Jo­erg Moeller

R&D chief Jo­erg Moeller, who gath­ered the reins in re­search af­ter the de­par­ture of An­dreas Busch in late 2017, told an in­vest­ment group in Lon­don Mon­day that the com­pa­ny was halt­ing its de­vel­op­ment work on vi­laprisan, a uter­ine fi­broid drug that has been billed as a top block­buster prospect at the com­pa­ny.

“For vi­laprisan we have just some days ago put clin­i­cal de­vel­op­ment of our on­go­ing tri­als on hold,” he not­ed, ac­cord­ing to a re­port in Reuters. “That is due to very re­cent safe­ty find­ings in long-term tox­i­col­o­gy stud­ies … We have there­fore de­cid­ed as a pre­cau­tion­ary mea­sure to stop en­roll­ment in­to our on­go­ing pro­gram and eval­u­ate the da­ta.”

I queried Bay­er about the is­sue, and got this back mid-morn­ing:

We re­cent­ly ob­served safe­ty sig­nals in pre-clin­i­cal tox­i­co­log­i­cal stud­ies in ro­dents in­ves­ti­gat­ing long term safe­ty of vi­laprisan – a drug can­di­date we de­vel­op for the treat­ment of uter­ine fi­broids and en­dometrio­sis.

Al­though these are pre­lim­i­nary pre-clin­i­cal find­ings that have not been ob­served in oth­er vi­laprisan stud­ies we de­cid­ed as a pre­cau­tion­ary mea­sure to pause re­cruit­ment in the on­go­ing clin­i­cal stud­ies with vi­laprisan un­til a thor­ough analy­sis of the find­ings has been achieved.

No new pa­tients will be en­rolled in the pro­gram. Pa­tients cur­rent­ly on treat­ment will con­tin­ue their on­go­ing treat­ment course ac­cord­ing to study pro­to­col un­til fur­ther no­tice from Bay­er.

Bay­er went on to note that they had alert­ed the prop­er au­thor­i­ties and will mon­i­tor pa­tients for safe­ty is­sues.

This isn’t the first uter­ine fi­broid ef­fort to raise alarms.

The set­back oc­curs as Al­ler­gan is still deal­ing with the FDA’s re­jec­tion of its uter­ine fi­broid drug Es­mya af­ter Eu­ro­pean reg­u­la­tors cit­ed it for trig­ger­ing a rare liv­er dis­ease. The EMA ear­li­er this year put re­stric­tions on the use of the drug to pro­tect women on the ther­a­py.

Ab­b­Vie, mean­while, has been rolling out Orilis­sa af­ter that drug was first ap­proved for en­dometrio­sis last Ju­ly. The ther­a­py has passed muster for uter­ine fi­broids in Phase III as well, rais­ing hopes that Ab­b­Vie can gain sig­nif­i­cant rev­enue from this drug as they ex­pand the mar­ket.

Bay­er, mean­while, is tran­si­tion­ing its R&D op­er­a­tions as it works out a glob­al re­struc­tur­ing, with plans to cut back on what it spends on in­ter­nal re­search in fa­vor of more al­liances with out­side bio­phar­ma com­pa­nies. A cou­ple of years ago, though, they in­clud­ed vi­laprisan among a group of drugs they tout­ed as like­ly block­busters able to earn more than $6 bil­lion in peak sales.

What hap­pened with the rest?

Their PI3k can­cer drug Aliqopa was first ap­proved a year ago, go­ing in­to a third-line set­ting against heavy com­pe­ti­tion. They have a high-risk heart drug called veri­ciguat, ane­tum­ab rav­tan­sine failed a mid-stage study for mesothe­lioma and no longer fea­tures on the late-stage end of the pipeline re­port and finerenone is in Phase III for kid­ney dis­ease, along­side daro­lu­tamide for can­cer. Daro­lu­tamide hit its goal in Phase III for non-metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer a cou­ple of months ago, though they held back all the da­ta for a lat­er con­fer­ence.

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Fol­low­ing news of job cuts in Eu­ro­pean R&D ops, Sanofi con­firms it’s of­fer­ing US work­ers an 'ear­ly ex­it'

Ear­li­er in the week we learned that Sanofi was bring­ing out the bud­get ax to trim 466 R&D jobs in Eu­rope, re­tool­ing its ap­proach to car­dio as re­search chief John Reed beefed up their work in can­cer and gene ther­a­pies. And we’re end­ing the week with news that the phar­ma gi­ant has al­so been qui­et­ly re­duc­ing staff in the US, tar­get­ing hun­dreds of jobs as the com­pa­ny push­es vol­un­tary buy­outs with a fo­cus on R&D sup­port ser­vices.

Suf­fer­ing No­var­tis part­ner Cona­tus is pack­ing it in on NASH af­ter a se­ries of un­for­tu­nate tri­al events

The NASH par­ty is over at No­var­tis-backed Cona­tus. And this time they’re turn­ing off the lights.

More than 2 years af­ter No­var­tis sur­prised the biotech in­vest­ment com­mu­ni­ty with its $50 mil­lion up­front and promise of R&D sup­port to part­ner with the lit­tle biotech on NASH — ig­nit­ing a light­ning strike for the share price — Cona­tus $CNAT is back with the lat­est bit­ter tale to tell about em­ri­c­as­an, which once in­spired con­fi­dence at the phar­ma gi­ant.

Bet­ter than Am­bi­en? Min­er­va soars on PhI­Ib up­date on sel­torex­ant for in­som­nia

A month af­ter roil­ing in­vestors with what skep­tics dis­missed as cher­ry pick­ing of its de­pres­sion da­ta, Min­er­va is back with a clean slate of da­ta from its Phase IIb in­som­nia tri­al.

In a de­tailed up­date, the Waltham, MA-based biotech said sel­torex­ant (MIN-202) hit both the pri­ma­ry and sev­er­al sec­ondary end­points, ef­fec­tive­ly im­prov­ing sleep in­duc­tion and pro­long­ing sleep du­ra­tion. In­ves­ti­ga­tors made a point to note that the ef­fects were con­sis­tent across the adult and el­der­ly pop­u­la­tions, with the lat­ter more prone to the sleep dis­or­der.

Gene ther­a­py biotech sees its stock rock­et high­er on promis­ing re­sults for rare cas­es of but­ter­fly dis­ease

Shares of Krys­tal Biotech took off this morn­ing $KRYS af­ter the lit­tle biotech re­port­ed promis­ing re­sults from its gene ther­a­py to treat a rare skin dis­ease called epi­der­mol­y­sis bul­losa.

Fo­cus­ing on an up­date with 4 new pa­tients, re­searchers spot­light­ed the suc­cess of KB103 in clos­ing some stub­born wounds. Krys­tal says that of 4 re­cur­ring and 2 chron­ic skin wounds treat­ed with the gene ther­a­py, the KB103 group saw the clo­sure of 5. The 6th — a chron­ic wound, de­fined as a wound that had re­mained open for more than 12 weeks — was par­tial­ly closed. That brings the to­tal so far to 8 treat­ed wounds, with 7 clo­sures.

Ab­b­Vie gets a green light to re­sume re­cruit­ing pa­tients for one myelo­ma study — but Ven­clex­ta re­mains un­der a cloud

Three months af­ter reg­u­la­tors at the FDA forced Ab­b­Vie to halt en­rolling pa­tients in its tri­als of a com­bi­na­tion us­ing Ven­clex­ta (vene­to­clax) to treat drug-re­sis­tant cas­es of mul­ti­ple myelo­ma, the agency has green-light­ed the re­sump­tion of one of those stud­ies, while keep­ing the rest on the side­lines.

The CANO­VA (M13-494) study can now get back in busi­ness re­cruit­ing pa­tients to test the drug for a pop­u­la­tion that shares a par­tic­u­lar ge­net­ic bio­mark­er. To get that per­mis­sion, Ab­b­Vie — which is part­nered with Roche on this pro­gram — was forced to re­vise the pro­to­col, mak­ing un­spec­i­fied changes in­volv­ing risk mit­i­ga­tion mea­sures, pro­to­col-spec­i­fied guide­lines and an up­dat­ed fu­til­i­ty cri­te­ria.

Bris­tol-My­ers star Op­di­vo fails sur­vival test in a matchup with Nex­avar aimed at shak­ing up the big HCC mar­ket

Bris­tol-My­ers Squibb has suf­fered an­oth­er painful set­back in its years-long quest to ex­pand the reach of Op­di­vo. The phar­ma gi­ant this morn­ing not­ed that their Check­mate-459 study com­par­ing Op­di­vo with Bay­er’s Nex­avar in front­line cas­es of he­pa­to­cel­lu­lar car­ci­no­ma — the most com­mon form of liv­er can­cer — failed to hit the pri­ma­ry end­point on over­all sur­vival.

This was a sig­nif­i­cant mile­stone in Bris­tol-My­ers’ tal­ly of PD-1 cat­a­lysts this year. Nex­avar (so­rafenib) has been the stan­dard of care in front­line HCC for the past decade, though Op­di­vo has been mak­ing head­way in sec­ond-line HCC cas­es, where it’s go­ing toe-to-toe with Bay­er’s Sti­var­ga (re­go­rafenib) af­ter re­cent ap­provals shook up the mar­ket.

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 more than a week 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.