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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Anthony Fauci (AP Images)

A press of­fi­cer at An­tho­ny Fau­ci’s NI­AID was un­masked as a hard-right Covid troll. He just re­tired to­day

William B Crews had been a public affairs specialist at the NIH’s National Institute of Allergy and Infectious Diseases.

That ended today when he informed the agency of his decision to retire, after he was identified as the managing editor at RedState, a prominent Trump loyalist website.

Crews’ RedState duties are performed under the alias streiff. While enjoying the benefits of pseudonymity, he disparaged and worked against NIAID with an incendiary level of rhetoric in the midst of a pandemic.

Donald Trump, AP

Covid-19 roundup: Trump sug­gests Pfiz­er vac­cine could be first ap­proved; VBI Vac­cines inks de­vel­op­ment deal with Cana­da

President Donald Trump commented Monday morning that Pfizer’s Covid-19 vaccine candidate could be the first to win approval by regulators.

During an interview on a Fox News’ morning show, the president said Pfizer was doing “very well” when asked which candidate could be approved, according to a Reuters report. He added that J&J could follow up afterward, saying “they’ll probably be a little later.”

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.