That Alzheimer's drug that flunked a PhII? On sec­ond look, Bio­gen/Ei­sai say it's a win­ner

Sev­en months ago, Bio­gen and Ei­sai were forced to aban­don their plans for a quick piv­ot in­to Phase III as their Alzheimer’s drug BAN2401 failed a de­ci­sive Phase II. Now, with the full 18-month analy­sis in hand, the part­ners are say­ing they were right to per­sist.

Bio­gen’s stock $BI­IB surged 17.48% in pre-mar­ket trad­ing on an up­dat­ed snap­shot, a con­sid­er­able boost giv­en the size of the com­pa­ny. So far, the com­pa­ny has added rough­ly $10 bil­lion to its mar­ket cap since yes­ter­day. Mean­while BioArc­tic, the small Swedish biotech whose re­search al­liance with Ei­sai first gave birth to the prod­uct, saw their shares (CPH: $BIOA-B) sky­rock­et 209% as of press time.

Here’s what changed: When eval­u­at­ed by the Alzheimer’s Dis­ease Com­pos­ite Score (AD­COMS), the high­est dose of BAN2401 showed to cause “sta­tis­ti­cal­ly sig­nif­i­cant slow­ing of dis­ease pro­gres­sion” af­ter 18 months of treat­ment. The tri­al re­cruit­ed 856 pa­tients with ear­ly Alzheimer’s dis­ease (and con­firmed amy­loid pathol­o­gy in the brain), a co­hort com­pris­ing those with mild cog­ni­tive im­pair­ment due to Alzheimer’s and oth­ers with mild Alzheimer’s de­men­tia.

Lynn Kramer, Ei­sai

What does this mean for a field fraught with fail­ures, a field that ab­sorbed the mil­lions of dol­lars thrown at it by big phar­mas and biotechs alike and churned out noth­ing in re­turn? While past fail­ures have re­peat­ed called the amy­loid hy­poth­e­sis — the idea that tar­get­ing the plaques ob­served in the brains of most Alzheimer’s pa­tients could change the tra­jec­to­ry of the dis­ease — in­to ques­tion, for Ei­sai CMO Lynn Kramer, their da­ta are “fur­ther val­i­dat­ing the amy­loid hy­poth­e­sis.” Some might al­so see it as a val­i­da­tion of ad­u­canum­ab, the much-tout­ed late-stage drug that’s al­so hit­ting the amy­loid be­ta path­way.

“We will dis­cuss these very en­cour­ag­ing re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the best path for­ward,” Kramer said in a state­ment.

It would be a huge feat to demon­strate im­prove­ment in cog­ni­tion linked with a de­cline in amy­loid be­ta clus­ters. But un­til the full da­ta is out at a fu­ture med­ical con­fer­ence, ex­perts are care­ful­ly man­ag­ing their ex­pec­ta­tions.

“Giv­en the state of the field we have to be cau­tious­ly op­ti­mistic about a find­ing like this,” Mayo Clin­ic Alzheimer’s Dis­ease Re­search Cen­ter di­rec­tor Ron Pe­tersen told Forbes.

Leerink’s Ge­of­frey Porges is more skep­ti­cal, point­ing out how lit­tle in­for­ma­tion was giv­en in the press re­lease.

We do not feel that Bio­gen, Ei­sai or the whole amy­loid field de­serves much cred­it for this dis­clo­sure, par­tic­u­lar­ly giv­en the lack of ex­ter­nal val­i­da­tion of the AD­COMS end­point. There is very lit­tle de­tail about oth­er more val­i­dat­ed cog­ni­tive mea­sures in the joint press re­lease and we find no rea­son to be­lieve this ei­ther proves or dis­proves the amy­loid hy­poth­e­sis or has any im­pact on the like­li­hood that ad­u­canum­ab will suc­ceed in its on­go­ing phase III tri­al.

A few de­tails in the tri­al de­sign may al­so prove prob­lem­at­ic.

For one, the turn­around comes down to sta­tis­tics. When Bio­gen and Ei­sai re­port­ed in De­cem­ber that the study failed its pri­ma­ry end­point, it was re­fer­ring to a Bayesian analy­sis, in which the drug would have to hit a cer­tain prob­a­bil­i­ty for caus­ing a cer­tain out­come to be deemed ef­fec­tive. Be­cause of that, and an adap­tive tri­al de­sign, re­searchers could make changes dur­ing the tri­al and pa­tients could be switched to dif­fer­ent dos­es. That didn’t work, so they wait­ed un­til the stan­dard 18-month mark to eval­u­ate the re­sults again with “con­ven­tion­al sta­tis­ti­cal meth­ods.” Look­ing back with this new frame­work, the part­ners now say their drug showed sta­tis­ti­cal­ly sig­nif­i­cant clin­i­cal ben­e­fit as ear­ly as six months.

The pos­i­tive out­come be­ing high­light­ed to­day al­so con­cerns on­ly the 10mg/kg bi­week­ly dose, which was one of five dos­es test­ed in the tri­al. It’s un­clear how many pa­tients end­ed up on that dos­ing scheme.

And fi­nal­ly there’s AD­COMS, the cho­sen mea­sure of cog­ni­tion, which was a nov­el end­point that com­bines a few stan­dard scales in Alzheimer’s.

But if there’s one thing we’re sure about, it’s that Bio­gen and Ei­sai are all in. The Japan­ese com­pa­ny re­cent­ly wa­gered more than $100 mil­lion on a be­spoke Alzheimer’s re­search cen­ter in its part­ner’s home of Cam­bridge, MA. And Bio­gen just tossed in an ex­tra $50 mil­lion for a big­ger slice of the roy­al­ties for ad­u­canum­ab.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.

Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

CEO Marco Taglietti (Scynexis)

'N­ev­er been more ur­gent:' Scynex­is looks to tack­le su­per­bug cri­sis with late-stage read­out for an­ti­fun­gal hope­ful

As the superbug crisis heats up around the world, Scynexis says it has new data from two interim analyses that prove its antifungal has the potential to treat a broad range of infections.

“The need for new anti-infectives capable of fighting the most resistant pathogens has never been more urgent as we confront the ongoing COVID-19 global pandemic,” CEO Marco Taglietti said in a statement.

A spot­light schiz­o­phre­nia drug in Neu­ro­crine's $2B Take­da deal flunks its first ma­jor test. But it's not giv­ing up yet

When Takeda spun out a pipeline of experimental psychiatry drugs to Neurocrine in a $2 billion deal amid a post-merger shakeout, R&D chief Andy Plump described the therapies as “very interesting but still difficult.”

On Tuesday, we got some idea of how difficult.

San Diego-based Neurocrine revealed that one of the three spotlight clinical programs they’d acquired failed the primary endpoint in a Phase II trial for schizophrenia, registering a negative outcome on the change from baseline in the positive and negative syndrome scale/negative symptom factor score (PANSS NSFS).

Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.