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.”

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.