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

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.

As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

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Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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In­cyte ponies up $12M to set­tle char­i­ty foun­da­tion kick­back claims; US ex­er­cis­es op­tion for more dos­es of mon­key­pox vac­cine

One in a string of lawsuits targeting copay charity foundations, the DOJ has been hunting drugmaker Incyte for what prosecutors alleged was a kickback scheme to court patients. Now, Incyte is clearing its name.

Incyte will shell out $12.6 million to settle claims it funneled funds through a charity foundation to cover federal copays for patients taking its JAK inhibitor Jakafi, the DOJ said this week.

UP­DAT­ED: EMA safe­ty com­mit­tee seeks more in­fo on heart in­flam­ma­tion fol­low­ing Pfiz­er Covid-19 vac­cine

The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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