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 clin­i­cal­tri­als.gov.

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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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