Bio­gen, Ei­sai fight back against ac­cu­sa­tions their big BAN2401 study was skewed -- but this fight is­n't over yet

Af­ter get­ting slapped hard by crit­ics for the way it han­dled their re­cent tri­al sum­ma­ry for their Alzheimer’s drug BAN2401, Ei­sai and their part­ners at Bio­gen $BI­IB turned up at an Alzheimer’s con­fer­ence in Barcelona to present their de­fense of the da­ta af­ter crunch­ing the num­bers again. But it’s not play­ing their way, with Bio­gen’s stock slid­ing as key an­a­lysts re­fused to for­give or for­get.

The two com­pa­nies man­aged to lose a lot of cred­i­bil­i­ty when an­a­lysts found out that at the re­quest of reg­u­la­tors — deeply con­cerned about the threat of ARIA-E — in­ves­ti­ga­tors pulled high-risk APOE4 car­ri­ers out of the high­est treat­ment arm in their study, cre­at­ing an im­bal­ance be­tween the drug group and place­bo that may have skewed the re­sults in the drug’s fa­vor.

To­day, the re­searchers are back af­ter ex­tract­ing the spe­cif­ic APOE4 re­sults in a close­ly-watched sub­group analy­sis, con­clud­ing:

At the high­est treat­ment dose, APOE4 car­ri­ers treat­ed with BAN2401 saw 63% less de­cline in dis­ease pro­gres­sion, while non-car­ri­ers saw 7% less de­cline, as mea­sured by AD­COMS ver­sus place­bo at 18 months. These re­sults sug­gest that the treat­ment ef­fect for the 10 mg/kg bi-week­ly dose is re­lat­ed to treat­ment with BAN2401 and not due to an im­bal­ance in sub­ject al­lo­ca­tion by APOE4 sta­tus. (Em­pha­sis added.) In ad­di­tion, the pooled 10 mg/kg bi-week­ly and 10 mg/kg month­ly dos­es re­sult in less de­cline on AD­COMS ver­sus place­bo at 18 months (over­all; 21%, APOE4 car­ri­ers; 25%, APOE4 non-car­ri­ers; 6%).

Clin­i­cal Ef­fects in APOE4 Car­ri­ers and Non-car­ri­ers at 18 Months (Page 20, Ei­sai slides)

Bio­gen’s shares dropped 2.6% on the lat­est da­ta. Why?

Both com­pa­nies clear­ly came out of the APOE4 con­tro­ver­sy with lost cred­i­bil­i­ty. Get­ting it back won’t be easy. And that was ev­i­dent in some re­marks from promi­nent an­a­lysts.

Baird’s Bri­an Sko­r­ney:

While the pre­sen­ters claim that this analy­sis re­solves out­stand­ing ques­tions around the mis­matched al­lo­ca­tion of APOE4+ pa­tients be­tween place­bo and treat­ment groups, we con­tin­ue to think that is­sues with tri­al de­sign and the fact of the im­bal­ance make the da­ta im­pos­si­ble to in­ter­pret, hence we find it dif­fi­cult to draw any con­clu­sions, much less the pos­i­tive ones Bio­gen and Ei­sai are in­fer­ring.

Count Ge­of­frey Porges, a skep­tic, as deeply dis­ap­point­ed by what was on dis­play to­day.

In our view this da­ta is con­fus­ing, sug­gest­ing on­ly lim­it­ed val­ue for BAN2401 in the car­ri­er pop­u­la­tion, while the small num­ber of pa­tients re­main­ing on drug at the 18-month time point and lack of clear dose re­spons­es di­min­ish the re­li­a­bil­i­ty of this dataset.

We are sur­prised by the lack of con­sis­tent ef­fect by ApoE4 sub­type, par­tic­u­lar­ly fol­low­ing ad­u­canum­ab da­ta ear­li­er this morn­ing show­ing rel­a­tive­ly con­sis­tent ef­fect in both car­ri­er and non-car­ri­er pop­u­la­tions. Ad­di­tion­al­ly we are dis­ap­point­ed that the ef­fect of low­er BAN2401 dose co­horts was not in­clud­ed in this analy­sis.

And…

Ei­sai showed that the low­er pro­por­tion of ApoE4+ sub­jects in the ac­tive drug arm com­pared to place­bo ac­tu­al­ly di­lut­ed BAN2401’s ef­fect since near­ly all of the ef­fi­ca­cy was dri­ven by the ben­e­fit in the ApoE4+ sub­pop­u­la­tion. How­ev­er, the num­ber of sub­jects re­main­ing in the analy­sis at 18 months was small (n=77 to­tal) and there were just 10 ApoE4+ sub­jects in­clud­ed in this analy­sis.

Ex­pect plen­ty of ad­di­tion­al feed­back on this one. All sub­group analy­sis is sub­ject to ques­tion. Some ob­servers have al­ready not­ed that you can’t pull out these com­par­isons on enough pa­tients to of­fer a clear pic­ture on out­comes rel­a­tive to APOE4. The com­pa­nies al­so came up with a new end­point to as­sess, which isn’t al­ways en­dorsed. And the high dose was clear­ly linked to a much high­er rate of ARIA-E, with 10% and 14% of the pa­tients in the two high­est dos­es suf­fer­ing from brain swelling, which won’t help its chances.

Bio­gen has a tremen­dous amount at stake here. There’s been a grow­ing cho­rus of crit­ics who say the da­ta are in­creas­ing­ly clear that symp­to­matic pa­tients can’t sig­nif­i­cant­ly ben­e­fit from any drug tar­get­ing amy­loid be­ta. And that makes their big play on ad­u­canum­ab in­creas­ing­ly risky.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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[via AP Images]

Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

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Tower Bridge in London [Shutterstock]

#UK­BIO19: Join GSK’s Hal Bar­ron and a group of top biotech ex­ecs for our 2nd an­nu­al biotech sum­mit in Lon­don

Over the past 10 years I’ve made a point of getting to know the Golden Triangle and the special role the UK biopharma industry plays there in drug development. The concentration of world class research institutes, some of the most accomplished scientists I’ve ever seen at work and a rising tide of global investment cash leaves an impression that there’s much, much more to come as biotech hubs are birthed and nurtured.