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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

President Donald Trump and FDA Commissioner Stephen Hahn (AP Images)

FDA is­sues fi­nal rule al­low­ing im­por­ta­tion of drugs from Cana­da — but al­so keeps the pow­er to re­voke it

Just over a month away from the presidential election, the FDA has issued a final regulation fulfilling President Trump’s promise to let states import certain prescription drugs from Canada.

On Thursday, Trump told a crowd in North Carolina that the new rule goes into effect “today.” But the published regulation states that it won’t take effect for 60 days. And even then, it could be a while before cheaper drugs make it across the border.

The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

Sil­ver­back dish­es out two pro­mo­tions in C-suite; Leg­end CEO post changes hands again

→ Accompanying the news that they just scored an $85 million Series C round, Laura Shawver-led Silverback Therapeutics has promoted two execs, with Valerie Odegard adding president to her CSO duties and Naomi Hunder moving to CMO. A Novo Nordisk alum, Odegard has been with the Seattle-based biotech since 2016 and the CSO the last 2 years. Before Silverback, she was VP of research at Juno Therapeutics.