FDA de­lays Bio­gen's ALS drug re­view by three months, de­ci­sion to now come next April

At­tempt­ing to push for­ward an ALS drug de­spite a failed Phase III study, Bio­gen saw its FDA re­view date de­layed Mon­day.

The big biotech an­nounced that the agency pushed back its de­ci­sion dead­line by three months to April 25, 2023 for tofersen, an an­ti­sense drug de­signed to treat a ge­net­ic sub­set of ALS. Bio­gen had pre­vi­ous­ly re­ceived pri­or­i­ty re­view for the ap­pli­ca­tion, which will fall un­der the ac­cel­er­at­ed ap­proval path­way.

In a press re­lease, Bio­gen said the FDA had re­quest­ed ad­di­tion­al in­for­ma­tion, but it’s not clear what they sought. A Bio­gen spokesper­son told End­points News, “We aren’t able to pro­vide fur­ther de­tail on our reg­u­la­to­ry in­ter­ac­tions, but in­for­ma­tion re­quests are a stan­dard part of the FDA re­view process.”

Bio­gen is try­ing to get tofersen ap­proved for ALS pa­tients with SOD1 ge­net­ic mu­ta­tions, a pop­u­la­tion that makes up rough­ly 2% of the glob­al pa­tient pop­u­la­tion. Though there are many genes known to be im­pli­cat­ed in ALS, SOD1 is the most com­mon. Cur­rent re­search es­ti­mates that all ge­net­ic mu­ta­tions ac­count for about 10% of ALS cas­es world­wide.

SOD1 falls un­der this um­brel­la, known as “fa­mil­ial ALS” due to its as­so­ci­a­tion with pa­tients’ fam­i­ly his­to­ries. The vast ma­jor­i­ty of oth­er ALS cas­es, called “spo­radic ALS,” make up the oth­er 90%, re­searchers be­lieve.

There have on­ly been three ALS drugs ap­proved by the FDA, all of which pro­vide on­ly mod­est ef­fects, and none are specif­i­cal­ly tar­get­ed to­ward fa­mil­ial cas­es. Tofersen at­tempts to slow SOD1-ALS pro­gres­sion by bind­ing to SOD1 mR­NA and re­duc­ing “syn­the­sis of SOD1 pro­tein pro­duc­tion,” the biotech says.

Us­ing a func­tion­al rat­ing scale mea­sur­ing pa­tient symp­toms as the pri­ma­ry goal, tofersen failed a Phase III test late last year. But Bio­gen is at­tempt­ing to win ac­cel­er­at­ed ap­proval based on the drug’s ef­fect on neu­ro­fil­a­ment light chain, an un­proven sur­ro­gate bio­mark­er that some re­searchers be­lieve can mea­sure neu­ronal cell death.

In pa­tients with neu­rode­gen­er­a­tive dis­eases, neu­ro­fil­a­ment lev­els can be el­e­vat­ed in blood and cere­brospinal flu­id. Bio­gen the­o­rizes that be­cause tofersen’s da­ta showed a low­er­ing of neu­ro­fil­a­ment dur­ing its clin­i­cal tri­als, the drug works, de­spite miss­ing the Phase III goals.

The FDA, how­ev­er, has nev­er ap­proved a drug based on its pur­port­ed neu­ro­fil­a­ment-low­er­ing ef­fect. Re­search show­ing neu­ro­fil­a­ment is im­pli­cat­ed in ALS is not con­clu­sive, though clin­i­cians note its promise. Oth­er bio­phar­ma com­pa­nies are like­ly watch­ing this case close­ly as well, to see if they can cen­ter their own new drug ap­pli­ca­tions around neu­ro­fil­a­ment.

Tofersen stands in con­trast to Re­lyvrio, the re­cent­ly ap­proved ALS drug from Amy­lyx Phar­ma­ceu­ti­cals, a Boston-area biotech. Where­as tofersen failed its Phase III while show­ing an ef­fect on neu­ro­fil­a­ment, Re­lyvrio earned a mod­est Phase II suc­cess — but showed no cor­re­la­tion to neu­ro­fil­a­ment lev­els.

That nu­ance has al­lowed Bio­gen to seek ac­cel­er­at­ed ap­proval while Amy­lyx was left search­ing for, and win­ning, a full green light. The ball is now in the FDA’s court, and if the path to ap­proval is any­thing like Amy­lyx’s, an ad­comm (or two) could be in Bio­gen’s fu­ture.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.

Alzheimer’s drug bites the dust; Re­struc­ture, re­struc­ture, re­struc­ture; Land­mark di­a­betes OK; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Being in the news business can give one a warped sense of time — it feels like quite a while since we published some of these stories below. But next Saturday’s Endpoints Weekly will definitely be shorter, as we take off Thursday and Friday for Thanksgiving. We will still have the abbreviated edition in your inbox at the usual time.

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Days af­ter re­port­ing PhI­II fail­ure, GSK pulls BC­MA drug from US mar­ket — but it's not giv­ing up en­tire­ly yet

GSK is pulling its BCMA-targeting drug from the US market, ending a short, two-year run for a high-profile product that, among other things, was hailed for marking the pharma giant’s return to oncology.

The company is initiating the process for withdrawal at the request of the FDA, which in turn was based on the negative readout of a confirmatory Phase III trial earlier this month. In that trial, GSK’s Blenrep failed to extend progression-free survival over standard of care for patients with multiple myeloma who have received at least two prior lines of therapy.

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MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.