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.

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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Turned back at the FDA, Im­muno­Gen is ax­ing 220 staffers, sell­ing pro­grams and hun­ker­ing down for a new PhI­II gam­ble

After being stymied by FDA regulators who were unconvinced by ImmunoGen’s $IMGN desperation shot at an accelerated OK based on a secondary endpoint, the struggling biotech is slashing its workforce, shuttering R&D projects and looking for buyers to pick up some of its experimental cancer assets as it goes back into a new Phase III with the lead drug.

We found out last month that the FDA had batted back their case for an accelerated approval of their antibody-drug conjugate mirvetuximab soravtansine, which had earlier failed a Phase III study for ovarian cancer. Now the other shoe is dropping.

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As­traZeneca chal­lenges Roche on front­line SCLC af­ter seiz­ing an in­ter­im win — and Mer­ck may not be far be­hind

The crowded playing field in the PD-1/L1 marketing game is about to get a little more complex.

This morning AstraZeneca reported that its CASPIAN study delivered a hit in an interim readout for their PD-L1 Imfinzi combined with etoposide and platinum-based chemotherapy options for frontline cases of small cell lung cancer, a tough target which has already knocked back Bristol-Myers’ shot in second-line cases. The positive data  — which we won’t see before they roll it out at an upcoming scientific conference — give AstraZeneca excellent odds of a quick vault to challenging Roche’s Tecentriq-chemo combo, approved 3 months ago for frontline SCLC in a landmark advance.

“This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options,” noted AstraZeneca cancer R&D chief José Baselga in a statement.

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Bridge­Bio takes crown for biggest biotech IPO of 2019, as fel­low uni­corn Adap­tive rais­es of­fer­ing size and price

Bridge­Bio Phar­ma and Adap­tive Biotech­nolo­gies have not just up­sized IPO of­fer­ings — the pair of uni­corns have al­so raised their of­fer­ing prices above the range, haul­ing in a com­bined $648.5 mil­lion.

Neil Ku­mar’s Bridge­Bio Phar­ma, found­ed in 2015, has a sta­ble of com­pa­nies fo­cused on dis­eases that are dri­ven by de­fects in a sin­gle gene — en­com­pass­ing der­ma­tol­ogy, car­di­ol­o­gy, neu­rol­o­gy, en­docrinol­o­gy, re­nal dis­ease, and oph­thal­mol­o­gy — and can­cers with clear ge­net­ic dri­vers. The start­up mill birthed a pletho­ra of firms such as Ei­dos, Navire, QED Ther­a­peu­tics and Pelle­Pharm, which func­tion as its sub­sidiaries.

Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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FDA re­jects Ac­er's rare dis­ease drug, asks for new tri­al — shares crater

Ac­er Ther­a­peu­tics’ bid to re­pur­pose celipro­lol — a be­ta-block­er on the mar­ket for hy­per­ten­sion — as a treat­ment for a rare, in­her­it­ed con­nec­tive tis­sue dis­or­der has hit a se­vere set­back. The New­ton, Mass­a­chu­setts-based com­pa­ny on Tues­day said the FDA re­ject­ed the drug and has asked for an­oth­er clin­i­cal tri­al.

The com­pa­ny’s shares $AC­ER cratered near­ly 77% to $4.47 in Tues­day morn­ing trad­ing.