Af­ter yet an­oth­er PhI­II Alzheimer's fail­ure, ex­perts try to map a path out of the wreck­ing field

Pushed by a 15-year record of clin­i­cal fail­ures and pulled by an FDA search­ing for a prac­ti­cal new path for­ward for Alzheimer’s drug re­search, a joint com­mit­tee or­ga­nized by the NIH’s Na­tion­al In­sti­tute of Ag­ing and the Alzheimer’s As­so­ci­a­tion is sug­gest­ing a bio­mark­er-based ap­proach to defin­ing the ill­ness that can guide new de­vel­op­ment ef­forts.

Eliez­er Masli­ah

In place of the old tox­ic pro­tein de­bate that once di­vid­ed the field in­to two camps for amy­loid be­ta and tau, the group be­lieves that the pres­ence of both should be a hall­mark of Alzheimer’s, along with phys­i­cal ev­i­dence of neu­rode­gen­er­a­tion or neu­ronal in­jury. By mix­ing and match­ing the bio­mark­ers, they want to be able to high­light the de­vel­op­ment of the dis­ease in­to a set of dis­tinct stages that can be used to test the ef­fec­tive­ness of new drugs and com­bi­na­tion ther­a­pies even be­fore symp­toms ap­pear.

So amy­loid be­ta by it­self would be ev­i­dence of dis­ease pathol­o­gy. Added to the pres­ence of tau you could di­ag­nose some­one as hav­ing Alzheimer’s. And signs of neu­rode­gen­er­a­tion could be used to high­light the ad­vance of the dis­ease. They’re al­so leav­ing the door open to oth­er bio­mark­ers for the dis­ease as re­search con­tin­ues and the field evolves.

By cen­ter­ing on bio­mark­ers that can be iden­ti­fied through brain imag­ing, along with a stan­dard ap­proach to defin­ing cog­ni­tion, they be­lieve they have a foun­da­tion to build a new wave of stud­ies that can find new drugs to help the mil­lions of peo­ple who un­know­ing­ly have the first tell­tale signs of a lethal dis­ease that wipes out a per­son’s mem­o­ries.

“We have to fo­cus on bi­o­log­i­cal or phys­i­cal tar­gets to ze­ro in on po­ten­tial treat­ments for Alzheimer’s,” ex­plained Eliez­er Masli­ah, di­rec­tor of the di­vi­sion of neu­ro­science at the NIA. “By shift­ing the dis­cus­sion to neu­ropatho­log­ic changes de­tect­ed in bio­mark­ers to de­fine Alzheimer’s, as we look at symp­toms and the range of in­flu­ences on de­vel­op­ment of Alzheimer’s, I think we have a bet­ter shot at find­ing ther­a­pies, and soon­er.”

Their pro­pos­al is crit­i­cal to a big R&D field that has been shak­en by a se­ries of ma­jor drug stud­ies that have gone far to prove that re­searchers don’t have a clear un­der­stand­ing of the bi­ol­o­gy of the dis­ease. 

Lon Schnei­der

“You can’t get around that peo­ple can have the pathol­o­gy of Alzheimer’s dis­ease and not have clin­i­cal symp­toms,” Lon Schnei­der, a re­searcher at USC’s Keck School of Med­i­cine, told me re­cent­ly as I ex­plored where the field was head­ed. “They can have a head full of amy­loid and be at risk of de­vel­op­ing de­men­tia,” but then nev­er ex­pe­ri­ence symp­toms of the dis­ease.

The news on Alzheimer’s R&D is all bad. Mer­ck’s re­cent de­ci­sive fail­ure on BACE, cut­ting off the sup­ply of amy­loid be­ta to the brains of pa­tients, has helped dis­prove a the­o­ry that has spurred bil­lions in fresh re­search spend­ing. Just yes­ter­day lit­tle vTv threw in the tow­el on an at­tempt to re­pur­pose a failed drug from Pfiz­er for the dis­ease, an­oth­er chron­ic los­er among var­i­ous de­vel­op­ment strate­gies. And Pfiz­er, af­ter spend­ing bil­lions of dol­lars on var­i­ous projects, opt­ed to sim­ply drop out, join­ing an in­dus­try re­treat that has al­ready claimed the li­on’s share of the work at As­traZeneca and Glax­o­SmithK­line. 

Richard Hodes

At the same time, the FDA has been en­cour­ag­ing the field to de­fine a stan­dard set or bio­mark­ers that could help de­fine a path for re­searchers to rea­son­ably de­fine the dis­ease and demon­strate progress in slow­ing it down, ahead of symp­toms de­fined by the gold stan­dard of Phase III pro­grams cen­tered on cog­ni­tion and func­tion. 

“In the con­text of con­tin­u­ing evo­lu­tion of Alzheimer’s re­search and tech­nolo­gies, the pro­posed re­search frame­work is a log­i­cal next step to help the sci­en­tif­ic com­mu­ni­ty ad­vance in the fight against Alzheimer’s,” said NIA Di­rec­tor Richard Hodes. “The more ac­cu­rate­ly we can char­ac­ter­ize the spe­cif­ic dis­ease process patho­log­i­cal­ly de­fined as Alzheimer’s dis­ease, the bet­ter our chances of in­ter­ven­ing at any point in this con­tin­u­um, from pre­vent­ing Alzheimer’s to de­lay­ing pro­gres­sion.”

Their work is in the April 10 is­sue of Alzheimer’s & De­men­tia: The Jour­nal of the Alzheimer’s As­so­ci­a­tion.

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan -- an­a­lysts turn thumbs down

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

AbbVie $ABBV has agreed to pay $188.24 a share — cash and stock — for the troubled Allergan, reflecting a 45% premium as investors bid up shares in anticipation of a much buzzed about company split. That price — with each share of Allergan worth 0.8660 AbbVie shares and $120.30 in cash — reflects a sharp fall from the $330 peak for Allergan and Saunders 4 years ago — but much better than anything shareholders had in mind for the near future.

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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.

With 4 more biotech IPOs due to wrap up Q2, how is the class of 2019 far­ing?

With 22 biotech IPOs on the books and four more set to price in the last week of June, in­vest­ment ad­vis­er Re­nais­sance Cap­i­tal has tak­en the pulse of the re­cent rush.

By the IPO ex­perts’ count, 25 out of 32 health­care of­fer­ings this year have been from biotechs — dif­fer­ing slight­ly from Brad Lon­car’s tal­ly — and the over­all pic­ture is one of un­der­per­for­mance. While they av­er­aged a first-day re­turn of 9.0%, col­lec­tive­ly they have trad­ed down to a 5.9% re­turn. Turn­ing Point $TP­TX and Cor­texyme $CRTX emerged on top at the half-year mark, ris­ing 135% and 109% re­spec­tive­ly.

Eye­ing a $500M peak sales pot, Almi­rall dou­bles down on le­brik­izum­ab as Der­mi­ra lines up PhI­II

With eyes on what it be­lieves is a $500 mil­lion peak rev­enue op­por­tu­ni­ty in Eu­rope, Barcelona-based Almi­rall has stepped up with $50 mil­lion in cash to take up the op­tion on Der­mi­ra’s IL-13 an­ti-in­flam­ma­to­ry drug le­brik­izum­ab just ahead of the start of Phase III. And there’s an­oth­er $30 mil­lion due as the late-stage pro­gram gets geared up.

That shouldn’t be long from now, as Der­mi­ra ex­pects to be­gin the late-stage tri­al work for atopic der­mati­tis be­fore the end of this year as it fol­lows a trail that ex­ecs in­sist leads to block­buster re­turns. Along the way, they’ll need to take on the 600-pound go­ril­la in atopic der­mati­tis: the IL-13/IL-4 drug Dupix­ent, from Re­gen­eron and Sanofi. Ri­vals al­so in­clude Leo Phar­ma, in its piv­otal with tralok­izum­ab, and Anap­tys­Bio in the hunt with a mid-stage pro­gram for etokimab, pre­vi­ous­ly re­ferred to as ANB020.

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.