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.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.

Ver­tex deal for Scot­land — no deal for Eng­land

Cystic fibrosis (CF) drug maker Vertex Pharmaceuticals — which is still locked in negotiation with NHS England to endorse the use of its medicines — has successfully negotiated a deal with Scottish authorities.

A month ago, the Scottish Medicines Consortium spurned two of the company’s medicines — Orkambi and Symkevi — citing uncertainty over their long-term efficacy in relation to their cost.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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