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.

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

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UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

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CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.