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

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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