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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Pfiz­er, Sarep­ta and two oth­ers sug­gest Duchenne drug safe­ty is­sues tied to "class ef­fect"

Since the first experimental Duchenne gene therapy programs came about, the space has proven rife with safety issues and patient deaths in clinical trials. Pfizer and three biotechs now think they’ve found a reason why.

The four companies suggested there may be a “class effect” causing the adverse events in Duchenne gene therapies, they wrote in a new study. They specifically highlighted how side effects in five patients across three trials, who all showed muscle weakness with cardiac involvement, were “strikingly similar.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

De­spite fed­er­al ef­forts to di­ver­si­fy clin­i­cal tri­als, progress re­mains 'stag­nan­t' — re­port

While calls to diversify clinical trials have grown louder in recent years — gaining support from federal agencies such as the FDA and NIH — progress has largely stalled, according to a new report from the National Academies of Sciences, Engineering and Medicine.

Swaths of patients in racial and ethnic minority groups, as well as LGBTQIA+, pregnant and older adult populations continue to be left out of clinical trials. While some advances have been made in the last 30 years — women now account for roughly half of clinical trial participants — growth in other areas remains stagnant, according to the report, which was mandated by Congress and sponsored by the NIH.

Paul Chaplin, Bavarian Nordic president and CEO

Bavar­i­an Nordic se­cures BAR­DA con­tract for small­pox vac­cine

It seems that smallpox vaccination production is weighing on the mind of the US government. And manufacturer Bavarian Nordic is the latest company to benefit.

Just a few days after Emergent, a company that has made government contracts its lifeblood, acquired the exclusive rights to Tembexa from Chimerix, with a $225 million cash payment and an expected BARDA contract, the agency has offered a contract for smallpox vaccine production.

Lina Khan, FTC chair (Saul Loeb/Pool via AP)

New FTC com­mis­sion­er could turn the tide for an in­ves­ti­ga­tion in­to PBMs

The Senate last week voted along party lines, 51-50, with Vice President Kamala Harris casting the tie-breaker, to make President Biden appointee Alvaro Bedoya the deciding vote on a split 2-2 Federal Trade Commission.

The addition of Bedoya to the FTC could not only spell more trouble for biopharma M&A activity, as he may align with his Democrat partners to break the FTC ties, but it may also mean that FTC Chair Lina Khan has what she needs to move forward on a study around the pharma middlemen known as pharmacy benefit managers.

Patty Murray (D-WA) (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.