Ax­o­van­t's lead Alzheimer's drug flops in PhI­II, end­ing an un­like­ly quest

Vivek Ra­maswamy burst on­to the biotech scene a few years ago with a brash plan to grab a failed drug from Glax­o­SmithK­line and hus­tle it straight in­to a piv­otal Phase III study for Alzheimer’s — a dis­ease that has de­feat­ed every piv­otal shot tak­en at it over the past 15 years.

But in­tepir­dine, like every oth­er Phase III Alzheimer’s study, failed. And this fail­ure for Ra­maswamy’s Ax­o­vant will like­ly kill 5HT6 as a tar­get in Alzheimer’s af­ter sev­er­al oth­er stud­ies with the same tar­get al­so flopped over the past year.

The news quick­ly crushed Ax­o­vant’s share price, send­ing it down more than 70% and wip­ing out $1.8 bil­lion in mar­ket cap in sec­onds as in­vestors re­act­ed to one of the biggest cat­a­lysts of the month.

Re­searchers said that the drug failed both co-pri­ma­ry end­points, un­able to sig­nif­i­cant­ly im­prove cog­ni­tion or func­tion for pa­tients rel­a­tive to place­bo. The key num­bers: ADAS-Cog (0.36 points, p=0.22) and AD­CS-ADL (0.09, p=0.83).

The com­pa­ny is stick­ing with top-line da­ta for now, plan­ning to out­line more of the specifics at an up­com­ing con­fer­ence. But in a call with an­a­lysts Tues­day, Ax­o­vant CEO David Hung made it clear that the drug com­bined with donepezil failed bad­ly.

“There was no dif­fer­ence be­tween the in­tepir­dine and the place­bo arms,” said Hung, and the Alzheimer’s pro­gram is fin­ished — though the com­pa­ny plans to pur­sue its work on de­men­tia with Lewy bod­ies.

The fail­ure here will come as no sur­prise to long­time in­ves­ti­ga­tors in the field. Pfiz­er and Lund­beck had both tried and failed to amp up cog­ni­tion with a 5HT6 pro­gram, de­signed to spur re­lease of a neu­ro­trans­mit­ter, though Ax­o­vant in­sist­ed that it could beat the odds.

If it had, an­a­lysts agreed that a new drug now could be worth bil­lions in an­nu­al rev­enue. In­stead, the drug hasn’t proven it’s worth the $5 mil­lion Ra­maswamy paid for it.

“While we are deeply dis­ap­point­ed by these tri­al re­sults, we al­so are sad­dened for the mil­lions of pa­tients and fam­i­lies im­pact­ed by Alzheimer’s dis­ease. How­ev­er, we be­lieve that the fight against Alzheimer’s and oth­er im­por­tant ar­eas of un­met need in neu­rol­o­gy is too im­por­tant to be de­railed by this set­back,” said Hung in a state­ment.

While the drug cost on­ly a few mil­lion up front to li­cense, the 32-year-old Ra­maswamy quick­ly steered Ax­o­vant $AX­ON in­to a record-set­ting biotech IPO on this drug, on his way to gath­er­ing close to $2 bil­lion to back a mul­ti-faceted en­ter­prise that has grown rapid­ly. He was able to re­cruit CEO Hung to take the helm not long af­ter Hung com­plet­ed the deal of a life­time in sell­ing Medi­va­tion to Pfiz­er for $14 bil­lion.

For Hung, it was a chance to take an­oth­er shot at Alzheimer’s, a dis­ease that had de­feat­ed one of his can­di­dates at Medi­va­tion.

Ra­maswamy had in­sist­ed that this drug would prove dif­fer­ent, point­ing to tri­al da­ta that showed a path for­ward. In­tepir­dine was his first test of a busi­ness mod­el that de­pends on gain­ing ac­cess to drugs on the shelves at the world’s biggest phar­ma com­pa­nies. But that mod­el faces fresh ques­tions this morn­ing as Ax­o­vant and the par­ent com­pa­ny — Roivant — deal with a bit­ter set­back.

Roivant put out a state­ment this morn­ing point­ing to all the oth­er drugs now in its mul­ti­ple pipelines. Ax­o­vant, the com­pa­ny not­ed, will con­tin­ue to in­ves­ti­gate new drugs for the mem­o­ry wast­ing ail­ment, just as it will con­tin­ue to go af­ter oth­er drugs. And with­out at­tri­bu­tion, the com­pa­ny says it will per­se­vere.

Some of those ef­forts will suc­ceed. Oth­ers will fail. We owe it to pa­tients to take those risks, and we re­main un­de­terred in pur­su­ing our mis­sion.


Im­age: Vivek Ra­maswamy Get­ty, David Hung File Pho­to

Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Flu Virus (Source: CDC)

FDA ex­pands Xofluza ap­proval as Roche strug­gles to catch loom­ing flu mar­ket

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

EMA backs sev­en ther­a­pies, in­clud­ing Mer­ck­'s Ebo­la vac­cine

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.

Ronald Herb­st fol­lows Med­Im­mune ex­o­dus to Pyx­is CSO post; Jeff God­dard to suc­ceed CEO of AIT Bio­science

→ The outflow of top execs from MedImmune continues to fill the leadership ranks of smaller biotechs. The latest to take off is Ronald Herbst, the head of oncology research, who’s assuming the CSO post at Pyxis Oncology.  

Herbst was part of the old MedImmune organization AstraZeneca CEO Pascal Soriot restructured earlier this year, reorganizing the company and eliminating the storied subsidiary as a separate organization.

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Mer­ck is tak­ing the ax to its US op­er­a­tions, cut­ting 500 jobs in its lat­est re­or­ga­ni­za­tion

Merck is cutting 500 jobs in its US sales and headquarters commercial teams in its latest effort to find new ways to streamline the operation.

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UP­DAT­ED: J&J's Xarel­to, Amar­in's Vas­cepa are cost-ef­fec­tive, not bud­get friend­ly — ICER

ICER, an increasingly influential cost-effectiveness watchdog in the United States, has concluded in its review of treatments for cardiovascular disease that while the cost of J&J’s Xarelto and Amarin’s Vascepa meet its benchmark for value pricing — the two treatments will not likely treat as many patients as hoped without surpassing the annual budget threshold calculated by ICER for each therapy.

Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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