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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

Jay Flatley, new Zymergen CEO

Fol­low­ing Au­gust melt­down, Zymer­gen hints at sal­vage plans — cut­ting jobs and rene­go­ti­at­ing loans

Two months after a spectacular implosion that saw its founding CEO leave his post amid customer reports its only product didn’t work, Zymergen provided the first peek behind the curtain for its plans moving forward.

In an SEC filing Wednesday, Zymergen told regulators it would slash about 100 jobs and had renegotiated a $100 million loan from Perceptive that loomed like a storm cloud over the company, moving up the maturity date 18 months to June 30, 2022. Jed Dean, one of Zymergen’s three co-founders and VP of operations, will also step down at the end of the month.

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Sanofi, Re­gen­eron etch out an­oth­er PhI­II vic­to­ry for Dupix­ent, eas­ing se­vere itch and clear­ing le­sions

Sanofi and Regeneron can boast of another inflammatory disease where Dupixent has proven effective.

The best-selling drug, which targets both IL-4 and IL-13, has delivered a clean sweep in a Phase III trial for prurigo nodularis, a chronic disease characterized by itch so intense that it can affect patients’ sleep and psychology. Thick skin lesions can cover most of the body.

On the primary endpoint, 37% of patients taking Dupixent saw a clinically meaningful reduction in itch compared to 22% of those on placebo (p=0.0216) at week 12. All secondary endpoints were also met, including clearance of skin lesions and improvement in quality of life.

David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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