Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Be­fore remde­sivir soaked up the spot­light amid the coro­n­avirus cri­sis, Gilead’s fil­go­tinib was the star ex­per­i­men­tal drug tapped to rake in bil­lions com­pet­ing with oth­er JAK in­hibitors made by ri­vals in­clud­ing Ab­b­Vie and Eli Lil­ly.

Now, long term da­ta on the drug — dis­cov­ered by Gilead’s part­ners at Gala­pa­gos and post­ed as part of a vir­tu­al med­ical con­fer­ence — have so­lid­i­fied the dura­bil­i­ty and safe­ty of fil­go­tinib in pa­tients with rheuma­toid arthri­tis, span­ning da­ta from three late-stage tri­als. An FDA de­ci­sion on the drug is ex­pect­ed this year.

Last Oc­to­ber, the com­pa­nies showed that the drug’s 52-week da­ta from the two main tri­als FINCH 1 and FINCH 3 were con­sis­tent with their 24-week re­sults. On Thurs­day, fur­ther analy­ses of the da­ta sug­gest­ed that pa­tients on the fil­go­tinib arm had a nu­mer­i­cal ad­van­tage in re­mis­sion rates.

At the 24-week cut­off, 48% of pa­tients en­rolled in the high­er 200 dose of fil­go­tinib arm were in re­mis­sion in the FINCH 1 tri­al that com­pared the drug to adal­i­mum­ab (Ab­b­Vie’s Hu­mi­ra). By the end of 52 weeks, that re­mis­sion rate rose to 52%. The per­cent­age in the Hu­mi­ra arm rose too, but the num­bers fa­vored fil­go­tinib across mul­ti­ple mea­sures of ef­fi­ca­cy. Da­ta from the FINCH 3 tri­al echoed that trend.

Fil­go­tinib’s biggest ri­val is Ab­b­Vie’s Rin­voq — the re­place­ment for its cash cow and world’s best sell­ing drug Hu­mi­ra. Rin­voq is slat­ed to be a block­buster, but car­ries the dread­ed black box warn­ing for throm­bo­sis, even though the event was rare in Ab­b­Vie’s de­vel­op­ment pro­gram.

The move by the FDA is more pre­cau­tion­ary giv­en that the JAK class of drugs has long been plagued by safe­ty con­cerns. Pfiz­er’s JAK1/JAK3 in­hibitor Xel­janz’s use has been blight­ed by reg­u­la­to­ry re­stric­tions af­ter the high­er dose of the block­buster drug was found to be as­so­ci­at­ed with the risk of blood clots and death. Eli Lil­ly’s JAK1/JAK2 Olu­mi­ant, mean­while, was ini­tial­ly re­ject­ed by the US agency due to safe­ty con­cerns — on­ly to even­tu­al­ly se­cure ap­proval for the low­er dose. Lil­ly’s part­ner, In­cyte, elect­ed to walk away from co-fund­ing the drug’s de­vel­op­ment as fears about the ben­e­fit-risk pro­file of the class of drugs ac­cu­mu­lat­ed.

Gala­pa­gos $GLPG, which once part­nered with Ab­b­Vie on fil­go­tinib, has pre­sent­ed it­self as a safer al­ter­na­tive to its ri­vals us­ing a pooled analy­sis of safe­ty da­ta com­piled from sev­en rheuma­toid arthri­tis tri­als. The analy­sis showed that the rate of ve­nous throm­boem­bolism, a key safe­ty con­cern, was low­er in pa­tients giv­en fil­go­tinib ver­sus those on place­bo.

“While filg’s pro­file has been quite clean so far, giv­en the his­to­ry of Jak in­hibitor ap­provals/re­jec­tions, we be­lieve the biggest risk to the pro­gram re­mains if any safe­ty im­bal­ances (even if seem­ing­ly mi­nor) emerge and de­rail ap­prov­abil­i­ty of the most ac­tive high dose (200mg) of the drug, or of the drug al­to­geth­er,” not­ed RBC Cap­i­tal Mar­kets an­a­lyst Bri­an Abra­hams in a note.

“In an­a­lyz­ing the de­tailed da­ta, we do not see any ma­jor new con­cerns and con­tin­ue to see a good like­li­hood of ap­proval, with a low se­ri­ous in­fec­tion rate pro­vid­ing a po­ten­tial safe­ty ad­van­tage vs. com­peti­tors. How­ev­er, we do see a slight im­bal­ance in over­all deaths for high­er vs. low­er dose fil­go­tinib that could be scru­ti­nized by the agency and may be a small risk to keep an eye on.”

Gilead paid $750 mil­lion up­front to part­ner with Gala­pa­gos years ago, ex­pand­ing the col­lab­o­ra­tion to an up-to $5.1 bil­lion deal last year. Fil­go­tinib, which is at the heart of the deal, is al­so be­ing test­ed for oth­er au­toim­mune con­di­tions such as Crohn’s dis­ease, ul­cer­a­tive col­i­tis and pso­ri­at­ic arthri­tis. Last Oc­to­ber it was re­vealed the drug failed mid-stage stud­ies in lu­pus and Sjö­gren’s dis­ease.

Janus ki­nase (JAK) in­hibitors are named af­ter the two-faced Ro­man god Janus and the fam­i­ly con­sists of four en­zymes: JAK1, JAK2, JAK3 and TYK2, which are as­so­ci­at­ed with cy­tokine re­cep­tors on the sur­face of cells and form part of a path­way in­volved in in­flam­ma­to­ry and im­mune re­spons­es.

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 commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Isaac Veinbergs, Libra CEO

With $29M in Se­ries A, Boehringer-backed Li­bra looks to tack­le neu­rode­gen­er­a­tion through cel­lu­lar clean­ing

Can the natural process by which cells clean out toxic proteins be harnessed to create potential treatments for neurodegenerative disorders?

That’s the question Libra Therapeutics will be trying to answer, as the new biotech officially launched Wednesday morning with $29 million in Series A financing. The company has three preclinical programs at the ready, with its lead candidate targeting ALS and frontotemporal dementia. But CEO Isaac Veinbergs said he hopes to develop therapies for a wide range of diseases, including Parkinson’s, Alzheimer’s and Huntington’s.

Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Gene Wang, Immetas co-founder and CEO (file photo)

Im­metas Ther­a­peu­tics nabs $11M Se­ries A to nar­row their bis­pe­cif­ic work tar­get­ing in­flam­ma­tion in age-re­lat­ed dis­eases

How does a biotech celebrate its two-year anniversary? For Immetas Therapeutics, it’s with an $11 million Series A round and a game plan to fight age-related disease.

Co-founders Gene Wang and David Sinclair came together years ago around the idea that inflammation is the ultimate process driving age-related illnesses, including cancer. The duo launched Immetas in 2018 and packed the staff with industry experts. Wang, who says he’s always had an entrepreneurial spirit, has held lead roles at Novartis, GSK, Bristol Myers Squibb and Merck. He’s worked on blockbuster drugs like Humira, Gardasil, Varubi and Zolinza. And now, he’s channeling that spirit as CEO.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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