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.

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

Top Har­vard chemist caught up in FBI’s 'T­hou­sand Tal­ents' drag­net, ac­cused of ly­ing about Chi­nese con­nec­tions, pay

The FBI’s probe into the alleged theft of R&D secrets by Chinese authorities has drawn Harvard’s top chemist into its net.

The agency accused Charles M. Lieber, who chairs the university’s chemistry and chemical biology department, with lying about his involvement in China’s Thousand Talents campaign, which was established as a way of drawing in innovators from around the world. And the scientist, 60, was charged with making false statements about his ties to China.

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Eye­ing a trio of tri­al ini­ti­a­tions, Jim Wilson's gene ther­a­py start­up woos Bruce Gold­smith from Deer­field as CEO

Passage Bio — Jim Wilson’s self-described “legacy company” — has wooed a seasoned biotech executive to steer the clinical entry of its first three gene therapy programs.

Bruce Goldsmith jumps to the helm of Passage after a brief CEO stint at Civetta, a cancer-focused startup he helped launch while a venture partner at Deerfield. He takes over from OrbiMed partner and interim chief Stephen Squinto, who will now lead the R&D team.

The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

UP­DAT­ED: Ac­celeron res­ur­rects block­buster hopes for so­tater­cept with pos­i­tive PhII — and shares rock­et up

Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

“We’re thrilled to report such positive topline results from the PULSAR trial,” Acceleron CEO Habib Dable said in a statement. The company said in a conference call they plan on discussing a Phase III trial design with regulators.

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Short at­tack­er Sahm Ad­ran­gi draws crosshairs over a fa­vorite of Sanofi’s new CEO — with PhII da­ta loom­ing

Sahm Adrang Kerrisdale

Kerrisdale chief Sahm Adrangi took a lengthy break from his series of biotech short attacks after his chief analyst in the field pulled up stakes and went solo. But he’s making a return to drug development this morning, drawing crosshairs over a company that’s one of new Sanofi CEO Paul Hudson’s favorite collaborators.

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Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”