Io­n­is, Akcea team face some tough ques­tions on safe­ty as FDA in­sid­ers pon­der risks linked to volane­sors­en

Re­searchers for Io­n­is’ $IONS ma­jor­i­ty-owned spin­out Akcea will have plen­ty of per­suad­ing to do this week if they ever ex­pect to get their drug volane­sors­en on the mar­ket.

The FDA in­ter­nal re­view came out to­day, re­flect­ing the same deep con­cerns that an­a­lysts have ex­pressed about the safe­ty of a drug that has been linked with re­peat­ed in­stances of sud­den and dan­ger­ous drops in platelet counts. Platelets are need­ed to trig­ger the clot­ting that stops bleed­ing.

Akcea’s shares $AK­CA im­me­di­ate­ly tum­bled 15% on the neg­a­tive tone of the in­ter­nal re­view.

James Smith

In a memo to the ad­vi­so­ry com­mit­tee meet­ing on Thurs­day, 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? That’s the big ques­tion that the de­vel­op­ers face this week. Reg­u­la­tors are 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. 

From Smith’s note:

Al­though the re­views high­light sev­er­al safe­ty/tol­er­a­bil­i­ty is­sues, the pri­ma­ry fo­cus for both the ap­pli­cant and the re­view­ers has been the risk of throm­bo­cy­tope­nia (low blood platelet counts) and re­sult­ing po­ten­tial for se­ri­ous bleed­ing….(S)ome pa­tients can ex­hib­it a rapid and un­pre­dictable re­duc­tion in platelets to ex­treme­ly low lev­els. In CS6, no pa­tients as­signed to place­bo had a platelet count fall be­low 100,000/uL com­pared with 18 (55%) of 33 pa­tients as­signed to volane­sors­en…Switch­ing to bi­week­ly dos­ing and/or dose in­ter­rup­tions have not al­ways led to a suf­fi­cient­ly time­ly re­cov­ery of platelet count; some pa­tients have re­quired treat­ment with pred­nisone, hos­pi­tal­iza­tion, and/or ad­min­is­tra­tion of IVIG. To date, se­ri­ous bleed­ing events have not been ob­served in this rel­a­tive­ly lim­it­ed safe­ty data­base, but the re­view­ers high­light a high­er risk of non-se­ri­ous bleed­ing-re­lat­ed ad­verse events with volane­sors­en (e.g., epis­taxis, pe­techi­ae). Some of these events oc­curred at platelet lev­els where spon­ta­neous bleed­ing would be un­ex­pect­ed, sug­gest­ing the pos­si­bil­i­ty of an ab­nor­mal­i­ty of platelet func­tion as well as an ef­fect on platelet count.

Io­n­is re­port­ed a lit­tle more that a year ago that it had achieved its ef­fi­ca­cy end­point in Phase III. But five pa­tients were forced out of the tri­al due to a threat­en­ing de­cline in platelet counts. Grade 4 throm­bo­cy­tope­nia oc­curred in three pa­tients, which end­ed af­ter they stopped dos­ing. There were no with­drawals due to platelet counts af­ter the com­pa­ny be­gan mon­i­tor­ing the side ef­fect.

If they do get an ap­proval, says Smith, it will have to come with a REMS. But right now, that looks like the best case sce­nario.

Nick Galakatos, Blackstone global head of life sciences

Nick Galakatos and the Black­stone team now have a record $4.6B to in­vest in bio­phar­ma, with a big fo­cus on push­ing com­pa­nies over the top

Nick Galakatos and his team at Blackstone Life Sciences have seen their biggest opportunities swell up in mostly established players who don’t have all the money they need to accomplish everything on the to-do list. And right now, with the industry booming, that’s a long list with some hefty needs.

The Blackstone team has neatly tied up the largest private fund ever raised in life sciences for making big dreams come true in biopharma. Late Thursday, Blackstone put out word that they had closed their highly anticipated fund with the projected $4.6 billion all in.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Top biotech an­a­lyst projects a gloomy out­look for Pfiz­er's JAK port­fo­lio

Many in the pharma world are hoping — better yet, expecting — JAK inhibitors to provide one of the next big boons for the industry. Few have invested as heavily in this area as Pfizer, which boasts a portfolio including Xeljanz and at least five mid-to-late stage candidates in the pipeline.

But a top Wall Street analyst is pumping the brakes on just how much good fortune is in store for the Big Pharma.

Gilead boasts of pos­i­tive remde­sivir da­ta on mor­tal­i­ty — but their analy­sis pro­vokes the skep­tics

Gilead is surging again off data that suggest its antiviral remdesivir might improve survival.

The new data come from an analysis Gilead conducted comparing the death rate and recovery time of patients in one of its remdesivir trials to a group of 800 patients “with similar baseline characteristics and disease severity” who received only standard-of-care around the same time. The result, they said, suggested that patients who received remdesivir had a 62% better chance at surviving than those who did not.

Hal Barron, GSK

Win or lose on the mar­ket­ing OK, the FDA just gunned down GSK’s bright hopes for their BC­MA ther­a­py

The FDA’s ODAC — the Oncologic Drugs Advisory Committee — has a well-known bias in favor of adding new cancer drugs to the market, even if efficacy is at best marginal and serious safety issues demand careful management.

Doctors want as many arrows in their quiver as they can get. And when patients are dying after failing multiple drugs, why not give it a go one more time?

GlaxoSmithKline, though, is about to test out how their new BCMA antibody drug conjugate belantamab mafodotin can do after being mauled in an in-house FDA review, ahead of the Tuesday expert panel discussion. Even if the agency goes ahead with an expected green light, this drug will likely be constrained to a small niche — icing any plans they may have for making waves in oncology anytime soon.

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Covid-19 roundup: BioN­Tech go­ing head-to-head with Mod­er­na as PhI­II mR­NA launch looms; Tri­al on Shin­zo Abe’s once-fa­vorite an­tivi­ral is in­con­clu­sive

It’s a race to the Phase III finish line now for the 2 leading mRNA vaccines in the pipeline for Covid-19.

BioNTech chief Ugur Sahin told the Wall Street Journal that his company will start Phase III testing of their vaccine later this month, setting them up to lateral the data to regulators before the end of this year.

That puts them essentially on the exact same schedule as Moderna is dedicated to. The Massachusetts rival to BioNTech also expects to launch Phase III this month. Lots of rumors have circulated about delays and conflict among the scientists advancing the Moderna jab, but the biotech has consistently stuck to its plan to start a late-stage pivotal this month.

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Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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An­oth­er four biotechs scratch out the first num­ber and ask for more as IPO boom con­tin­ues

Four more biotechs are raising their offers in an already record year for biotech IPOs.

Softbank-backed Relay Therapeutics scratched out its original $200 million filing and proposed a $250 million raise that would make them a $1.5 billion company. CAR-T developer Poseida Therapeutics bumped itself up $74 million to $224 million. Off-the-shelf cell therapy startup Nkarta upped from $150 million to $215 million — and then priced even higher, at $252 million. France’s Inventiva did its own modest reset, raising its bar from $102 million to $108 million.

Oph­thalmic drugs, can­cer cell ther­a­pies at­tract $340M+ on two HKEX biotech de­buts

Nasdaq may be running the main biotech IPO show, but the Hong Kong stock exchange has some stellar performance on display even as the city confronts a third wave of Covid-19.

Ocumension Therapeutics and Immunotech Biopharm both traded up after making their public debuts on the HKEX’s busiest IPO day of the year so far, with seven stocks getting listed. The former raised close to $200 million while the latter took home $141 million.