Zaf­gen has some­thing to cheer as di­a­betes drug makes the cut in PhII study

Af­ter be­ing plagued by a laun­dry list of set­backs that cul­mi­nat­ed in the de­ser­tion of its obe­si­ty drug and the de­par­ture of its CEO, Zaf­gen fi­nal­ly has some good news to re­port. Da­ta from a co­hort of a mid-stage study sug­gest­ed that its now-lead di­a­betes drug in­duced sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in blood sug­ar lev­els and weight loss.

The Boston-based com­pa­ny’s shares $ZFGN rose about 7% in pre-mar­ket trad­ing on Thurs­day.

More than two years ago Zaf­gen aban­doned de­vel­op­ing be­lo­ranib af­ter the ex­per­i­men­tal obe­si­ty drug was linked to pa­tient deaths in a late-stage study. The FDA, wor­ried about ex­pos­ing more pa­tients to harm, slapped a clin­i­cal hold on Zaf­gen’s sec­ond-gen­er­a­tion di­a­betes drug ZGN-1061 last No­vem­ber, wary that the car­dio threat posed by be­lo­ranib was still in play. At the time, Zaf­gen said ex-US Phase II clin­i­cal tri­al of ZGN-1061 would con­tin­ue as planned, and that it would talk to the FDA staff to de­ter­mine the path for­ward.

Den­nis Kim

On Thurs­day, the com­pa­ny re­port­ed en­cour­ag­ing da­ta from the two high­est dos­es of the di­a­betes drug, fol­low­ing up on ear­li­er pos­i­tive re­sults with small­er dos­es. Ac­cord­ing to US clin­i­cal tri­als data­base, the Phase II proof-of-con­cept study in­clud­ed two groups of pa­tients. In the first co­hort, 120 pa­tients would get ei­ther 0.05, 0.3, or 0.9 mg of ZGN-1061 or place­bo, while in the sec­ond co­hort, 40 pa­tients would re­ceive 0.9 or 1.8 mg of ZGN-1061 or place­bo.

No treat­ment-re­lat­ed se­ri­ous side-ef­fects and no car­dio­vas­cu­lar safe­ty sig­nals were ob­served in the sec­ond co­hort of the study, the com­pa­ny said.

Leerink’s Joseph Schwartz did not let the com­pa­ny off the hook, how­ev­er, say­ing al­though Zaf­gen did not ob­serve any clin­i­cal­ly mean­ing­ful el­e­va­tions in mean D-dimer con­cen­tra­tions — a key bio­mark­er for CV risks — he was cau­tious ahead of phase III stud­ies in­volv­ing larg­er and het­ero­ge­neous type 2 di­a­betes pa­tient pop­u­la­tion on mul­ti­ple oth­er agents.

The com­pa­ny did not dis­close how the drug en­ters and ex­its en­dothe­lial cells, Schwartz not­ed, in ref­er­ence to con­cerns he had pre­vi­ous­ly high­light­ed re­gard­ing pre­clin­i­cal da­ta on the com­pound, which sug­gests it has the propen­si­ty to in­duce clot­ting fac­tors if it is not cleared from en­dothe­lial cells, and the po­ten­tial for drug-drug in­ter­ac­tions.

In terms of ef­fi­ca­cy, 12-week da­ta sug­gest­ed that the 1.8 mg dose sur­passed the glycemic con­trol in­duced by the 0.9 mg dose, but both dos­es con­ferred a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in A1C — a blood test that mea­sures av­er­age lev­els of blood glu­cose (p<0.0001 and p=0.0003, re­spec­tive­ly). The high­est dose caused a 1.1% re­duc­tion in A1C rel­a­tive to place­bo.

“The re­sults we’ve seen…with this lat­est 1.8 mg dose co­hort, ap­pear very com­pet­i­tive with the cur­rent­ly avail­able best-in-class an­ti-di­a­betes ther­a­pies,” Zaf­gen CMO Den­nis Kim said in a state­ment. “All of the phar­ma­co­log­i­cal ac­tions of ZGN-1061 im­prove at the 1.8 mg dose lev­el and, with its in­sulin-sen­si­tiz­ing ef­fects, we be­lieve there is a clear op­por­tu­ni­ty for even greater ben­e­fit with longer treat­ment du­ra­tion giv­en the ef­fect we are see­ing at just 12 weeks.”

Sig­nif­i­cant­ly, treat­ment with the 1.8 mg dose al­so trig­gered a place­bo-cor­rect­ed weight loss of 2.3 kg (5.1 pounds) that was sta­tis­ti­cal­ly sig­nif­i­cant (p=0.0002), Zaf­gen said, adding that there was no ev­i­dence of a wan­ing ef­fect.

“These re­sults in con­junc­tion with meta­bol­ic ben­e­fits along­side a pro­gres­sive re­duc­tion in weight po­si­tion ZGN-1061 com­pet­i­tive­ly with those agents al­ready ap­proved,” Schwartz added in a note.

Di­a­betes and obe­si­ty are close­ly linked — some drugs to treat the lat­ter have been pulled off the mar­ket due to safe­ty con­cerns, and those that have man­aged to re­main on shelves have seen mea­ger adop­tion, due to their lim­it­ed ef­fec­tive­ness, bun­gled launch­es and re­im­burse­ment hur­dles.

Last year, Zaf­gen saw big man­age­ment changes, in­clud­ing the ex­its of CEO Tom Hugh­es, who had led the com­pa­ny for 9 years, and board mem­ber Bruce Booth, who made his de­par­ture af­ter a dozen years.

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.