As Ei­sai, Bio­gen plot a course to ac­cel­er­at­ed ap­provals for Alzheimer’s drug, a mob of skep­tics are wait­ing to de­ci­pher hard num­bers

Wel­come to the big cat­a­lyst of Q3.

Ei­sai and Bio­gen won’t re­veal their da­ta from a mid-stage study of BAN2401 in Alzheimer’s dis­ease un­til to­mor­row, but there’s no ques­tion that they’re pre­sent­ing this as a ma­jor break­through in the field that needs to be hus­tled to pa­tients as rapid­ly as pos­si­ble.

Now they just have to con­vince a le­gion of prac­ticed, long­time skep­tics that they’re right. 

Lynn Kramer

In an in­ter­view with Reuters, Ei­sai’s chief med­ical of­fi­cer for neu­rol­o­gy, Lynn Kramer, told re­porters that the part­ners are al­ready lay­ing the ground­work for a broad late-stage pro­gram while tak­ing this drug to reg­u­la­tors in search of an ac­cel­er­at­ed ap­proval.

“There is a clear dose re­sponse,” says Kramer, who’s ev­i­dent­ly itch­ing to re­veal how many pa­tients in the study got the high dose of the drug. In ad­di­tion, he added that low­er dos­es al­so worked.

So why aren’t an­a­lysts lin­ing up to cheer the first ma­jor break­through in Alzheimer’s in well over a decade?

Michael Ehlers

First, the study failed the pri­ma­ry end­point at 12 months us­ing Bayesian analy­sis of the da­ta. But Bio­gen R&D chief Michael Ehlers — who was re­luc­tant to say ahead of talks with reg­u­la­tors just what the next clin­i­cal step will be — told in­vestors Tues­day morn­ing that they found a sig­nif­i­cant “dis­ease mod­i­fy­ing ef­fect” of their drug with “be­ta amy­loid low­er­ing in the brain” us­ing more tra­di­tion­al sta­tis­ti­cal analy­sis at 18 months. There was al­so a “dose de­pen­dent slow­ing of the rate of clin­i­cal pro­gres­sion…as ear­ly as 6 months and 12 and 18 months.”

So it’s a break­through, right?

It’s not that easy.

To­mor­row we’ll find out ex­act­ly what Ei­sai and Bio­gen con­sid­er to be a sta­tis­ti­cal­ly sig­nif­i­cant re­sponse. That leaves an­a­lysts spec­u­lat­ing on the num­bers, look­ing for a range on the slow­ing rate of dis­ease pro­gres­sion with the range ex­tend­ing any­where from 10% to 40%.

At 10%, ex­pect plen­ty of skep­ti­cism. Mizuho an­a­lysts wouldn’t be sur­prised at 15% slow­ing.  

Ge­of­frey Porges, Leerink

But wait. Leerink’s more skep­ti­cal Ge­of­frey Porges be­lieves that any­thing un­der 15% is like­ly to be seen as a weak re­sponse, with dam­ag­ing re­sults for the de­vel­op­ers’ stocks. Any­thing over 30% will dri­ve a ma­jor ral­ly, on top of the one al­ready seen on the topline da­ta.

What’s the big deal here?

Af­ter more than a decade of fail­ure by all the ma­jors, a suc­cess here would sin­gle-hand­ed­ly re­vive the amy­loid be­ta the­o­ry be­hind Alzheimer’s, which has be­come in­creas­ing­ly doubt­ful as tri­al af­ter tri­al has now shown that tar­get­ing a-be­ta doesn’t re­sult in im­prove­ments in cog­ni­tion and func­tion. To bend the curve on this dis­ease — which af­flicts mil­lions — would hand Ei­sai and Bio­gen the gold­en tick­et in lot­tery R&D, like­ly open­ing a mar­ket that could be worth $10 bil­lion a year. It would al­so help im­prove sen­ti­ment for Bio­gen’s oth­er Alzheimer’s drug, ad­u­canum­ab.

Josh Schim­mer

There are some com­pli­cat­ing fac­tors, though, which they have to clear. One big hur­dle in­volves the unique Alzheimer’s test set up by the re­searchers, which they say bet­ter cap­tures the ef­fect of the drug on pa­tients with a mild form of the dis­ease. But any­thing that veers from the straight and nar­row in Alzheimer’s re­search may at­tract crit­i­cal as­sess­ments by the reg­u­la­to­ry groups asked to re­view it.

In ad­di­tion, some ex­perts in the field are won­der­ing how the post-fail­ure de­c­la­ra­tion of suc­cess was han­dled in­ter­nal­ly, and if any bi­as­es were in­tro­duced in­to the study that could have af­fect­ed out­comes.

What won’t pass muster here is any kind of hype over the num­bers. If the com­pa­nies her­ald weak da­ta, they will be dragged over the coals by an­a­lysts who have seen the same thing hap­pen over and over again at com­pa­nies that were lat­er forced to ad­mit de­feat.

(Any­one re­mem­ber Eli Lil­ly CEO John Lech­leit­er’s en­thu­si­asm for solanezum­ab — af­ter its sec­ond big late-stage fail­ure, paving the way for a third flop?)

“If the BAN2401 Alzheimer’s da­ta shows well, it could dri­ve a lift in sen­ti­ment and in­flow of cap­i­tal for the sec­tor broad­ly,” Ever­core ISI an­a­lyst Josh Schim­mer told Mar­ket­Watch, “so our fin­gers are crossed that BI­IB wouldn’t be so ridicu­lous as to put out a clear­ly pos­i­tive press re­lease with­out a dataset that is clear­ly ro­bust.”

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

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Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

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The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

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Seattle Genetics $SGEN is showing off more positive data around tucatinib, its pivotal-stage drug for HER2 positive breast cancer.

A month after hearing about solidly upbeat hazard ratios, we learned today that the estimated progression-free survival rate at one year was 33% in the tucatinib arm compared to 12% for patients taking trastuzumab and capecitabine alone.

Median PFS was 7.8 months (95% CI: 7.5, 9.6) in the tucatinib arm, compared to 5.6 months (95% CI: 4.2, 7.1) in the control arm.

Bat­tered, cash hun­gry In­tec feels the burn of No­var­tis re­jec­tion

It’s a case of some bad timing for Intec.

Just when a key trial testing the company’s Accordion drug delivery tech imploded in Parkinson’s disease, they handed Novartis data from a successful PK study of a custom Accordion pill engineered to deliver a Novartis compound to entice the Swiss drugmaker into signing a licensing agreement.

Novartis said thanks, but no thanks.

For the cash-strapped Israeli drug developer, the failure to clinch the deal marks a big blow. As of the third quarter, the company has $15.7 million in cash and equivalents, which HC Wainwright analysts estimate will keep the lights on into mid-2020.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

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De­sert­ed by Astel­las and Mer­ck, lit­tle Cor­re­vio still can't win over FDA pan­el con­cerned with its AFib drug's safe­ty

When the FDA spurned Astellas’ pitch for atrial fibrillation drug vernakalant in 2008, regulators made it abundantly clear that it wasn’t the efficacy they had a problem with — two Phase III trials had shown the drug successfully restored 52% of patients’ heartbeat from irregular to normal — but the cardio safety issues for a drug that was to compete with well established, low-risk options. One licensing deal, one clinical hold and several studies later, the chances of approval aren’t looking any better.

New trade deal knocks out long-sought patent pro­tec­tions for drug­mak­ers

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