PhII fail­ure in rare neu­rode­gen­er­a­tive dis­ease? No mat­ter, Bio­gen will mo­tor on in Alzheimer's

Bio­gen’s fierce fo­cus on dis­or­ders of the brain has hit an­oth­er road­block.

On Fri­day, the US drug­mak­er — which re­cent­ly res­ur­rect­ed its amy­loid-tar­get­ing Alzheimer’s drug, ad­u­canum­ab — said its an­ti-tau drug, go­suranemab, failed a mid-stage study in pa­tients with pro­gres­sive supranu­clear pal­sy (PSP), a rare brain dis­or­der that re­sults from de­te­ri­o­ra­tion of brain cells that con­trol move­ment and thought.

Bio­gen, which li­censed the mon­o­clon­al an­ti­body from Bris­tol-My­ers Squibb, said it is aban­don­ing test­ing the drug in PSP pa­tients, but will con­tin­ue to in­ves­ti­gate its use in Alzheimer’s pa­tients with mild cog­ni­tive im­pair­ment, giv­en dif­fer­ences in dis­ease pathol­o­gy, it said.

In pa­tients with PSP, the build-up of tau typ­i­cal­ly oc­curs in the frontal cor­tex. While in Alzheimer’s, tau tends to ac­cu­mu­late in the hy­po­thal­a­mus and brain stem.

“It’s un­clear what the pre­cise im­pli­ca­tions are from the PSP fail­ure – we’re sure Bio­gen will con­duct in-depth analy­ses – but on the sur­face, it leads us to ques­tion the vi­a­bil­i­ty of tar­get­ing in­tra-cel­lu­lar tau with an an­ti­body. The ba­sic premise be­hind the tau an­ti­body ap­proach is to pre­vent the “spread­ing” of tau from neu­ron to neu­ron, though as we un­der­stand it, at a giv­en time point, very lit­tle tau is sit­ting out­side of the cell, and most mis­fold­ed tau is path­o­gen­ic in­side neu­rons,” Stifel’s Paul Mat­teis wrote in a note.

“Thus, we would view these da­ta in PSP – which is the­o­ret­i­cal­ly an en­riched in­di­ca­tion for test­ing the tau an­ti­body hy­poth­e­sis – as al­so neg­a­tive for the prospects of Bio­gen’s tau pro­gram in Alzheimer’s, giv­en that the lat­ter is more het­ero­ge­neous, and the same po­ten­tial ‘an­ti­body tar­get ac­cess is­sues’ may al­so be a rel­e­vant chal­lenge.”

Bio­gen did not of­fer much de­tail on the failed PASS­PORT study, ex­cept to say go­suranemab had failed to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in the PSP rat­ing scale at week 52 — the main study goal — and that it had al­so dis­ap­point­ed in key clin­i­cal sec­ondary end­points.

Ex­pec­ta­tions for the PSP pro­gram were al­ready low, Cred­it Su­isse’s Evan Seiger­man wrote in a note.

“Tau tar­get­ing as­sets have so far been dif­fi­cult to de­vel­op (Ab­b­Vie dis­con­tin­ued its pro­gram in PSP due to lack of ef­fi­ca­cy). De­spite ev­i­dence of CSF free tau sup­pres­sion, it re­mains a chal­lenge to prove how this trans­lates in­to clin­i­cal ben­e­fit,” he said. “The com­pa­ny plans on con­tin­u­ing the de­vel­op­ment of ‘092 in Alzheimer’s dis­ease ‘due to dif­fer­ences in dis­ease pathol­o­gy,’ but as we were with PSP have low con­fi­dence in the pro­gram.”

The go­suranemab study in Alzheimer’s pa­tients, dubbed TAN­GO, has en­rolled over 650 pa­tients with an es­ti­mat­ed pri­ma­ry com­ple­tion date of May 2021, ac­cord­ing to clin­i­cal­tri­

But the quest for treat­ments to pre­vent and treat Alzheimer’s, the most com­mon form of de­men­tia, is lit­tered with fail­ure. For long, re­searchers were par­tial to the amy­loid hy­poth­e­sis, which sug­gests that tar­get­ing be­ta-amy­loid plaques that col­lect be­tween neu­rons and dis­rupt cell func­tion could make a ma­te­r­i­al im­pact on the pro­gres­sion of the dis­ease.

How­ev­er, set­back af­ter set­back seem­ing­ly put the nail in the amy­loid cof­fin ear­li­er this year af­ter Bio­gen, one of the last flag bear­ers of the the­o­ry ac­knowl­edged their fail­ure. But in a dra­mat­ic twist in Oc­to­ber, Bio­gen in­di­cat­ed it had res­ur­rect­ed its faith in the amy­loid the­o­ry, at least in a sub­set of pa­tients, fol­low­ing a pro­tract­ed pe­ri­od of da­ta min­ing.

Mean­while, re­searchers are al­so look­ing at tau. Ini­tial­ly, an­ti-tau ther­a­pies were fo­cused on in­hibit­ing ki­nas­es or tau ag­gre­ga­tion, or on sta­bi­liz­ing mi­cro­tubules (which help guide nu­tri­ents and mol­e­cules from the cell body to the ax­on and den­drites) — but most of these ap­proach­es have been aban­doned due to tox­i­c­i­ty or a lack of ef­fi­ca­cy, or both. Sci­en­tists are now look­ing at de­vel­op­ing tau-tar­get­ing im­munother­a­pies.

Janet Woodcock (AP Images)

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Janet Woodcock is set to be the most powerful person at the FDA in less than a week.

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The appointment was requested by the incoming Biden team, Karlin-Smith added, as they sort out the nomination of a permanent successor to Stephen Hahn — whose one-year tenure has been defined by Covid-19.

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Janet Woodcock (AP Images)

Janet Wood­cock is in the run­ning for FDA com­mis­sion­er — what does that mean for the agen­cy's fu­ture?

Just a day after reports emerged that Janet Woodcock will serve as interim chief of the FDA, word has gotten out that she is also in the running for the permanent job.

The decision, as the initial wave of reactions suggest, could have dramatic implications for where the agency is headed in the next four years — if not beyond.

Woodcock, the longtime CDER director, is being vetted alongside former FDA principal deputy commissioner Joshua Sharfstein, Bloomberg reported. Already tapped as acting head of the agency, she’s set to take over from Stephen Hahn right after Biden’s inauguration next week.

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CEO Brett Monia (Ionis)

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Monia, one of the handful of young scientists who in 1989 followed Stanley Crooke across the country from SmithKline (now GSK) in Philadelphia to found Ionis in Northern California, replaced Crooke as CEO last January. By then, they had proven antisense, an RNA-based method for manipulating gene expression, could work dramatically well in at least some instances, transforming spinal muscular atrophy with the Biogen-partnered blockbuster Spinraza.

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Steve Harr (L) and Hans Bishop

Paint­ing by the num­bers, Sana founders carve up a gi­ant uni­corn-sized IPO — for a biotech that has­n't quite made it to the clin­ic

Sana Biotechnology is one of those startups that was sketched in on the chalkboard day one in the shape of a unicorn.

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And from the numbers the cell therapy 2.0 play spelled out in their S-1 $SANA, it’s clear that the company founders — led by a pair of major VCs aligned with some high-profile industry figures — are hunting a big chunk of that value for themselves.

The raise they penciled in — $150 million — isn’t likely what they actually have in mind, and it doesn’t do justice to the size of their ambitions.

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Terry Rosen, Arcus CEO

Gilead part­ner Ar­cus earns an­a­lyst­s' plau­dits for ear­ly pan­cre­at­ic can­cer da­ta that 'ex­ceed­ed ex­pec­ta­tion­s'

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David Kessler in April 2009 (Eric Risberg/AP Images)

Covid-19 roundup: Hack­ers start re­leas­ing 'ma­nip­u­lat­ed' Covid-19 vac­cine docs; Ex-FDA com­mish David Kessler to re­place Mon­cef Slaoui as Op­er­a­tion Warp Speed chief — re­port

There’s a new twist on the EMA Covid-19 hacking story.

Friday the European agency put out the 5th in a series of statements about the hackers who broke into their system, noting that some of the information on vaccines that was gleaned in the attack is showing up online — altered to raise questions about the Covid-19 vaccines now in use.

This included internal/confidential email correspondence dating from November, relating to evaluation processes for COVID-19 vaccines. Some of the correspondence has been manipulated by the perpetrators prior to publication in a way which could undermine trust in vaccines.

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With KRAS break­through on the hori­zon, Am­gen's David Reese re­flects on so­tora­si­b's loom­ing re­view date and murky fu­ture

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Amgen filed its FDA application for sotorasib in December to treat metastatic non-small cell lung cancer with the KRAS mutation — once thought to be “undruggable” — months after the agency offered its breakthrough designation based on pivotal Phase I data showing previously unheard of response rates.

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News brief­ing: Five Prime fi­nal­izes PhI­II plans for gas­tric can­cer; AI di­ag­nos­tics-fo­cused Paige ex­pands staff

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The South San Francisco-based biotech released full Phase II data for bemarituzumab on Friday, which Five Prime said in November met all of its pre-specified efficacy endpoints in a topline readout. Now, the company is announcing it plans to launch a Phase III trial for the program in 2021. Following November’s readout, the future of bemarituzumab had not yet been finalized.

Peter Thiel, Getty (Photographer: Kiyoshi Ota/Bloomberg)

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Billionaire Peter Thiel has made significant and sometimes controversial pushes into life sciences over the past few years, and one of his startups out of Berlin has made a new acquisition less than two months after achieving unicorn status.

ATAI Life Sciences purchased a majority stake Tuesday in Recognify Life Sciences, a company focused on developing treatments for cognitive impairment associated with schizophrenia. The financial terms of the deal weren’t disclosed, but the acquisition follows up a $125 million Series C in November co-led by Thiel, leading to a post-money valuation of about $1 billion for ATAI.