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.

RWE chal­lenges for to­day's bio­phar­ma

The rapid development of technology — and the resulting avalanche of data — are catalysts for significant change in the biopharmaceutical industry. This translates into urgent pressures for today’s biopharma, including a need to quickly and affordably develop products with proven therapeutic efficacy and value. This urgency is expedited by the growth of value-based contracting, where access to reimbursement and profit depends on these abilities.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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As shares suf­fer from a lin­ger­ing slump, a bruised Alk­er­mes slash­es 160 jobs in R&D re­struc­tur­ing

With its share price in a deep slump after suffering through a regulatory debacle over their depression drug ALKS 5461, Alkermes CEO Richard Pops is taking the ax to its R&D organization in a restructuring aimed at cutting costs ahead of its next attempt at a rollout in a tough field.

Richard Pops, Endpoints via Youtube

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Acor­da's Ron Co­hen brings the ax back out as new drug sales on­ly trick­le in while cash cow is led to the slaugh­ter

With its new drug earning meager sums and its one-time cash cow reduced to a bony shadow of its former self, Acorda Therapeutics today is rolling out a new restructuring aimed at slashing the staff and cutting costs to get through the hard times ahead.

The biotech is chopping a quarter of its staff today, carving back R&D as well as SG&A expenses. And CEO Ron Cohen is cutting deep.

Under the new austerity budget, Acorda’s R&D expenses for the full year 2019 are expected to be $55 – $60 million, reduced from $70 – $80 million. SG&A expenses for the full year 2019 are expected to be $185 – $190 million, reduced from $200 – $210 million. R&D expenses for the full year 2020 are expected to be $20 – $25 million and SG&A
expenses for the full year 2020 are expected to be $160 – $165 million.

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RAPT Ther­a­peu­tics re­turns to Wall Street to re­vive IPO bid

On May 24, FLX Bio, a small cancer and inflammation biotech with backing from GV, changed its name to RAPT Therapeutics and filed confidentially for an IPO. On July 5th, they filed to raise up to $86 million. On July 22, they announced the IPO with a $75 million goal.  And on August 1, they abruptly and without explanation called it all off.

Now, without explanation, they’re reviving the bid, filing again for a $75 million IPO, this time with a new bookrunner and a new drug candidate in the clinic. The terms will be the same: 5 million shares at $14-$16 per share. It would give them a diluted market value of $351 million.

EY vet set to re­place re­tir­ing Am­gen CFO Meline

Ahead of its third-quarter results next week, Amgen on Tuesday disclosed the planned retirement of David Meline, who has served as the company’s chief financial officer since 2014.

Meline will be replaced by Ernst & Young vet, Peter Griffith, as CFO come January 1, 2020 — but until then Griffith will serve as executive vice president, finance.

“Over the last 5 years at Amgen, Meline instituted many major changes that led to operational efficiencies and margin expansion while successfully returning cash to shareholders. Now that Amgen is on solid footing, it was a good time to step away,” Cowen’s Yaron Werber wrote in a note. “We do not anticipate any major changes to strategy or operations immediately due to this transition as Amgen is on solid footing.”

Eli Lil­ly’s USA, di­a­betes chief En­rique Con­ter­no is head­ing out af­ter 27 years, and he’s be­ing re­placed by a com­pa­ny in­sid­er

Close to 3 years after Eli Lilly CEO Dave Ricks added the title of president of the US operations to Enrique Conterno’s resume, which included his helmsmanship of the diabetes franchise, the Peruvian born exec is set to retire after a 27-year run at the pharma giant.

Lilly put out the news just as it was posting Q3 results, with a mix of upbeat and downbeat results in the latest set of numbers from Lilly.
Conterno — a grizzled, deeply experienced and sometimes gruff veteran of the pharma world — was a high-profile figure at Lilly, stepping up to expanded duties as the company was forced to deal with intense pricing pressure on the diabetes side of the business. He had replaced outgoing US president Alex Azar, who later popped up as head of Health and Human Services in the Trump administration.
As head of the diabetes unit, Conterno had to deal with an extraordinarily competitive field as payers demanded bigger discounts. Trulicity’s success helped generate new revenue for the company, but Q3’s miss on revenue had a lot to do with the need for discounting the drug ahead of Novo Nordisk’s rival therapy, Rybelsus, which was priced on the wholesale level at an almost identical rate.

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No­var­tis hands off $80M in cash to part­ner up with a top biotech play­er in the fi­bro­sis sec­tor

Never underestimate the power of a good showing at a scientific conference.
In a presentation late last year, the researchers at Pliant Therapeutics launched a series of discussions about the preclinical data they were pulling together around their work on their small-molecule integrin inhibitor aimed at transforming growth factor beta, or TGF-β, a key pathway involved in fibrosis.
And they got some serious attention for the work.
“We got interest from pharma partners and at the end Novartis basically made it,” says Pliant CEO Bernard Coulie.

Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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