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.

Take­da swoops in to buy lit­tle biotech part­ner and its celi­ac drug poised to 'change stan­dard of care'

Having spent three years carefully grooming PvP Biologics and its drug for celiac disease, Takeda is happy enough with the proof-of-concept data to buy it all.

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Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Mi­cro­bio­me Q&A: New study maps the vagi­na's 'op­ti­mal mi­cro­bio­ta' — and its im­pli­ca­tions for bio­phar­ma

The widely-held notion that the “optimal” vaginal microbiota is dominated by one strain of lactic-acid producing bacteria has now been challenged in a new paper, published in Nature Communications on Wednesday, which used advanced gene sequencing methods to map out the most comprehensive gene catalog of the human vaginal microbiome.

Things have changed in the more than 50 years since the concept of vaginal microbiota transplants was proposed and subsequently tainted by a Texas-based gynecologist who transplanted the vaginal fluid of women who had bacterial vaginosis into healthy females, suspecting he had isolated the bacteria responsible for the condition.

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Fol­low­ing US, Chi­na hos­pi­tal ef­forts, Gilead plots its own PhI­II tri­als for close­ly watched Covid-19 drug

Gilead is launching its own Phase III trials of remdesivir, the repurposed antiviral that a WHO official called the “one drug right now we think may have real efficacy” against Covid-19 as the novel coronavirus originating from Wuhan, China ravages the world.

Announced just a day after the NIH and the University of Nebraska Medical Center registered their US-based trial online, Gilead’s program will comprise two studies enrolling around 1,000 patients beginning in March. They will recruit primarily in Asian countries but will also include patients from other locations with “high numbers of diagnosed cases,” the company said.

Bio­gen touts new ev­i­dence from the gene ther­a­py com­pa­ny it wa­gered $800M on

A year ago, Biogen made a big bet on a small gene therapy company. Now they have new evidence one of their therapies could work.

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Anthony Fauci (AP Images)

UP­DAT­ED: NIH-part­nered Mod­er­na ships off its PhI-ready coro­n­avirus vac­cine can­di­date to a sea of un­cer­tain­ty

Off it goes.

Moderna has shipped the first batch of its mRNA vaccine against SARS-CoV-2 from its manufacturing facility in Norwood, Massachusetts, to the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, for a pioneering Phase I study.

It’s a hectic race against time. In the 42 days since Moderna selected the sequence they would use to develop their vaccine — a record time, no less — the number of confirmed cases around the world has surged astronomically from a few dozen to over 80,000, per WHO and Johns Hopkins estimates.

The candidate that they came up with, mRNA-1273, encodes for a prefusion stabilized form of the spike protein, which gives the virus its crown shape and plays a key role in transmission. The Coalition for Epidemic Preparedness Innovations, the Oslo-based group better known as CEPI, funded the manufacture of this batch.

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In at least one life-sci hub, gen­der and di­ver­si­ty ini­tia­tives haven’t made a dent

Gender and racial diversity at the top of UK life science companies has hardly budged over the last seven years despite repeated advocacy efforts, according to a new report.

The report, from the recruiting firm Liftstream, found that 14.8% of directors on life sciences boards were women and 21.1% of top executives were women. That’s a modest bump from the 9.8% of directors and 18.1% of executives Liftstream identified in their last report from 2014. The percentage of women CEOs moved from 8% to 9.8%.

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Will a 'risk-of­f' mind­set has­ten cell ther­a­py M&A? Io­vance surges on buy­out chat­ter

Is it time for some cell therapy M&A?

Investors of Iovance Biotherapeutics certainly thought so, sending its stock $IOVA up as much as 40% after Bloomberg reported that the cancer-focused biotech is talking to potential buyers.

While 2019 saw a number of high-profile gene therapy company takeovers — led by Roche’s $4.3 billion bid of Spark as Astellas went for Audentes, Biogen snapped up Nightstar and Vertex absorbed Exonics — large players appeared to prefer partnering on the cell therapy front, particularly when it comes to cancer. Hal Barron put his weight behind Rick Klausner’s startup as he rebuilt GlaxoSmithKline’s cancer pipeline. Takeda turned to MD Anderson to license their natural killer cell therapy.

One less ri­val for Im­muno­vant, as Alex­ion aban­dons FcRn in­hibitor

Less than one year after Alexion parted with $25 million upfront to secure access to a second anti-FcRn asset, it is abandoning the experimental drug. The discontinuation, disclosed at the SVB Leerink Global Healthcare Conference in New York during a fireside chat, bodes well for rival Immunovant.

The drug (ABY-039), partnered for development with Sweden’s Affibody, was forsaken on the basis of early-stage data that was not viewed favorably, Baird and SVB Leerink analysts noted.