FDA re­view rais­es some se­ri­ous ques­tions for Puma, but shares rock­et up on pos­i­tive notes

Puma Biotech­nol­o­gy will face some tough ques­tions from reg­u­la­tors dur­ing Wednes­day’s long-await­ed pan­el re­view for its ex­per­i­men­tal can­cer drug ner­a­tinib.

Not on­ly did the FDA re­view, out this morn­ing, raise point­ed ques­tions about the many changes that were made to Puma’s study for ear­ly-stage ERBB2-pos­i­tive breast can­cer, it al­so high­light­ed — as ex­pect­ed — the high rate of se­ri­ous di­ar­rhea ex­pe­ri­enced by pa­tients in the study.

One crit­i­cal is­sue: At one point, just four months be­fore Puma filed for an ap­proval, reg­u­la­tors al­so ad­vised Puma ex­ecs against fil­ing for an OK.

Pre-NDA meet­ing with Puma – FDA ad­vised they did not en­cour­age an NDA sub­mis­sion based on the ef­fi­ca­cy and safe­ty re­sults of Study 3004. This was due to sev­er­al study con­duct is­sues which would make in­ter­pre­ta­tion of the re­sults prob­lem­at­ic. The Ap­pli­cant was ad­vised that if an NDA was sub­mit­ted, an On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee dis­cus­sion would be re­quired.

At the same time, reg­u­la­tors did not con­demn the drug, not­ing that even with the ar­ray of changes to the study, there is da­ta sup­port­ing ef­fi­ca­cy. And the bulls ran with the win com­bined with an over­all neu­tral tone to the prob­lems Puma may face. Its shares $PBYI rock­et­ed up 80%, then quick­ly slid back down to a 50% gain on a sec­ond take of the re­view.

In its sum­ma­ry, the FDA not­ed that:

De­spite the un­planned amend­ments and po­ten­tial un­cer­tain­ty in­tro­duced with re­spect to the mag­ni­tude of ner­a­tinib ef­fect, based on the sen­si­tiv­i­ty analy­ses con­duct­ed, the re­sults ap­pear to be gen­er­al­ly sim­i­lar to the pri­ma­ry analy­sis re­sults, sup­port­ing an ef­fect of ner­a­tinib.

The FDA set up a rel­a­tive­ly short pan­el re­view for Wednes­day, which had trig­gered spec­u­la­tion from a host of short sell­ers who have dogged this biotech at every step that Puma was in line for a thump­ing. But as of now, that’s all it is.

Reg­u­la­tors not­ed, though, that they have con­cerns with the re­sults from the study.

There re­mains some un­cer­tain­ty re­gard­ing the true mag­ni­tude of the treat­ment ef­fect since the pri­ma­ry analy­sis (trun­cat­ed at 2-years fol­low-up) ob­served a haz­ard ra­tio of 0.66 (95% CI: 0.49, 0.90) which changed to 0.68 (95% CI: 0.51, 0.91) with the ex­plorato­ry up­dat­ed 2-year analy­sis and the ex­plorato­ry 5-year analy­sis ob­served a haz­ard ra­tio of 0.73 (95% CI: 0.57, 0.92).

Puma has been pil­lo­ried rou­tine­ly for the way it han­dled the se­vere in­stances of di­ar­rhea in its stud­ies. As the re­view notes, even with the ad­di­tion of an an­tidiar­rheal drug in Puma’s stud­ies there was still a high rate of dropouts.

While there were few­er dose re­duc­tions and dose holds in the Lop­eramide Co­hort of Study 6201 com­pared to pa­tients in Study 3004, there re­mained a sub­stan­tial rate of dis­con­tin­u­a­tion due to di­ar­rhea de­spite an­tidiar­rheal pro­phy­lax­is with Lop­eramide (16.8% in Study 3004 and 20.4% in Study 6201). In ad­di­tion, a high­er in­ci­dence of con­sti­pa­tion and nau­sea was re­port­ed in the Lop­eramide co­hort.

The FDA re­view should raise some ob­vi­ous ques­tions on Wednes­day. But the ju­ry still re­mains out on Puma’s fate. Matthew Eck­ler at RBC looked over the docs and saw much to be hap­py with.

In our ini­tial read, we didn’t come across any­thing that we view as over­ly sur­pris­ing. As ex­pect­ed, the FDA doc­u­ments read as harsh in some sec­tions (many FDA brief­ing books can), but ul­ti­mate­ly we see the points raised as hav­ing al­ready been wide­ly known in­clud­ing: 1) the clin­i­cal sig­nif­i­cance of iDFS ben­e­fit seen in Ex­teNET; 2) changes made to the de­sign of Ex­teNET; 3) Ner­a­tinib-as­so­ci­at­ed G3 di­ar­rhea; and 4) ben­e­fit of ner­a­tinib in the HR+ sub­group. We al­so note that we don’t see any men­tion of Aphin­i­ty in the FDA brief­ing book. The bot­tom line is that the FDA doc­u­ments read very bal­anced to us, and are frankly more pos­i­tive than we an­tic­i­pat­ed, set­ting the stage ODAC to make an un­am­bigu­ous rec­om­men­da­tion.

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.

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.

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.

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.

Alex­ion wins pri­or­i­ty re­view for Ul­tomiris' aHUS in­di­ca­tion; FDA ex­pands ap­proval of Ver­tex's Symdeko

→ Alex­ion $ALXN has scored a speedy re­view for Ul­tomiris for pa­tients with atyp­i­cal he­molyt­ic ure­mic syn­drome (aHUS) af­ter post­ing pos­i­tive da­ta from a piv­otal study in Jan­u­ary. The drug is the rare dis­ease com­pa­ny’s shot at pro­tect­ing its block­buster blood dis­or­der fran­chise that is cur­rent­ly cen­tered around its flag­ship drug, Soliris, which is a com­ple­ment in­hibitor typ­i­cal­ly ad­min­is­tered every two weeks. Ul­tomiris has a sim­i­lar mech­a­nism of ac­tion but re­quires less-fre­quent dos­ing — every eight weeks. The de­ci­sion date has been set to Oc­to­ber 19. Late last year, Ul­tomiris se­cured ap­proval for noc­tur­nal he­mo­glo­bin­uria (PNH) pa­tients.

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.