Io­n­is, Akcea just got hand­ed a one-way tick­et to the end of the reg­u­la­to­ry line as the FDA re­jects volane­sors­en

Io­n­is $IONS and its sis­ter or­ga­ni­za­tion at Akcea have just been slammed with an un­ex­pect­ed re­jec­tion of volane­sors­en, their drug for reg­u­lat­ing plas­ma triglyc­eride for pa­tients with rare cas­es of fa­mil­ial chy­lomi­crone­mia syn­drome.

What hap­pened?

Sim­ply put, we don’t know. All Io­n­is and Akcea $AK­CA did was put out a state­ment re­peat­ing some of their ear­li­er talk­ing points in fa­vor of the drug, which man­aged to pass muster at the ex­pert pan­el meet­ing that was called to re­view it. They didn’t say why the drug was re­ject­ed or what they have to do to win reg­u­la­tors over.

But we can guess. 

The agency’s in­ter­nal re­view raised some daunt­ing ques­tions about their drug’s safe­ty pro­file. 

In a memo to the ad­vi­so­ry com­mit­tee meet­ing, James Smith, the deputy di­rec­tor of the Di­vi­sion of Me­tab­o­lism and En­docrinol­o­gy Prod­ucts, spot­light­ed a gen­er­al agree­ment that the drug has a clear­ly pos­i­tive ef­fect on reg­u­lat­ing plas­ma triglyc­eride for pa­tients with rare cas­es of fa­mil­ial chy­lomi­crone­mia syn­drome. That’s a sur­ro­gate end­point for the dis­ease.

But is the ben­e­fit re­al­ly worth the risk of bleed­ing, af­ter the drug was linked to sud­den and un­ex­pect­ed drops in platelet counts?

Reg­u­la­tors were al­so some­what per­plexed by Akcea’s wish to switch the dos­ing reg­i­men and their platelet mon­i­tor­ing strat­e­gy to some­thing that was nev­er test­ed in the clin­i­cal tri­als.

The agency’s ex­pert pan­el con­sid­ered those is­sues, and vot­ed 12 to 8 in fa­vor of an ap­proval — the kind of en­dorse­ment that car­ries par­tic­u­lar­ly heavy weight for rare dis­eases. As a re­sult, in­vestors weren’t ex­pect­ing any of this. Akcea’s shares plunged 30% on the news, while Io­n­is’ stock dived more than 13%.

Paul Mat­teis at Stifel looked at the tea leaves and not­ed:

AK­CA was close to the vest on the na­ture of the CRL mak­ing it dif­fi­cult for us to know what the path for­ward is for Waylivra lead­ing us to re­move val­u­a­tion cred­it. How­ev­er, we do know from the ad­comm that the FDA was fo­cused the risk of platelet de­clines and with Waylivra’s over­all risk/ben­e­fit pro­file. We think the main in­vestor ques­tion on this an­nounce­ment will be re­gard­ing read-through to Tegse­di. Our as­sump­tion for Tegse­di ap­proval re­mains un­changed giv­en (1) it’s ap­proval in EU and (2) it’s stronger dataset, in our view – based on clean­er safe­ty/ef­fi­ca­cy con­veyed on mea­sures of dis­ease symp­to­ma­tol­ogy, in­clud­ing qual­i­ty-of-life.

This morn­ing Al­ny­lam caught a re­lief ral­ly as it be­came ap­par­ent that Pfiz­er would have to fight for every inch of their rare dis­ease mar­ket niche in AT­TR. That left Io­n­is’ and Akcea’s ri­val ther­a­py in an un­com­fort­able third place post. That helped make Mon­day a tough time for these two com­pa­nies.


This day just keeps get­ting worse for these two close­ly al­lied com­pa­nies, which are very un­hap­py this evening.

“We are ex­treme­ly dis­ap­point­ed with the FDA’s de­ci­sion. FCS is an ul­tra-rare and de­bil­i­tat­ing dis­ease. Our dis­ap­point­ment ex­tends to the pa­tient and physi­cian com­mu­ni­ty who cur­rent­ly do not have a treat­ment avail­able to them. We con­tin­ue to feel strong­ly that WAYLIVRA demon­strates a fa­vor­able ben­e­fit/risk pro­file in peo­ple with FCS as was re­flect­ed in the pos­i­tive out­come from our Ad­vi­so­ry Com­mit­tee hear­ing in May. We will con­tin­ue to work with the FDA to con­firm the path for­ward,” said Paula Soteropou­los, Akcea’s chief ex­ec­u­tive.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

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Tim Van Hauwermeiren, argenx CEO

Ar­genx pur­chas­es $100M+ FDA pri­or­i­ty re­view vouch­er from blue­bird bio

Argenx’s Vyvgart is due for a speedy review at the FDA, thanks to a $102 million priority review voucher (PRV).

The Netherland-based biotech picked up the PRV from bluebird bio, the companies announced on Wednesday. PRVs shorten a drug’s FDA review period from 10 months to 6 months, though they often sell on the open market for around $100 million each.

Argenx plans on using the express ticket on efgartigimod, its neonatal Fc receptor (FcRn) blocker marketed as Vyvgart for adults with generalized myasthenia gravis (gMG). While Vyvgart won its first approval last December for the chronic neuromuscular disease — which is characterized by difficulties with facial expression, speech, swallowing and breathing — CEO Tim Van Hauwermeiren said in a news release that he plans to “be active in fifteen disease targets by 2025.”