Ham­mered hard by a sur­pris­ing FDA re­jec­tion, Io­n­is spin­out Akcea of­fers an ex­pla­na­tion and then chops 1-in-10 staffers

Akcea re­port­ed in an SEC fil­ing Thurs­day af­ter­noon that it is chop­ping 10% of its work­force as a re­sult of the FDA’s sur­prise re­jec­tion of volane­sors­en, their drug for reg­u­lat­ing plas­ma triglyc­eride for pa­tients with rare cas­es of fa­mil­ial chy­lomi­crone­mia syn­drome. The pink slips were hand­ed out the same day at the biotech, which is run by CEO Paula Soteropou­los.

The com­pa­ny al­so of­fered its first ac­knowl­edg­ment of what went wrong, and how it hopes to deal with the cri­sis.

 

The com­pa­ny, a spin­out from Io­n­is $IONS — which still has a con­trol­ling in­ter­est in Akcea — had been ex­tra­or­di­nar­i­ly tight lipped about its af­flic­tions, ini­tial­ly un­will­ing to spell out any rea­sons for the re­jec­tion. A ma­jor­i­ty of FDA ex­perts on the pan­el re­view ac­tu­al­ly vot­ed in fa­vor of mar­ket­ing ap­proval. But in a sur­prise turn­around the agency it­self is­sued a com­plete re­sponse let­ter 10 days ago.

Fol­low­ing up with the com­pa­ny Thurs­day night, a spokesper­son for Akcea said that they have out­lined what went wrong. In a note to End­points News, she not­ed:

Re­gard­ing the CRL, we said in our pub­licly we­b­cast pre­sen­ta­tion at Wells Far­go yes­ter­day that the is­sues raised are con­sis­tent with what was dis­cussed at the Ad­Comm and are re­lat­ed to da­ta on man­ag­ing platelet lev­els and dos­ing.  We hope to ad­dress this with da­ta from our on­go­ing Open La­bel Ex­ten­sion study and/or Ear­ly Ac­cess Pro­gram, but we will not know the spe­cif­ic path for­ward or if this will be a suf­fi­cient ap­proach un­til we meet with the FDA. We hope to do that as soon as pos­si­ble. FCS is a de­bil­i­tat­ing dis­ease with no ther­a­peu­tic op­tions. We con­tin­ue to be­lieve WAYLIVRA demon­strates a pos­i­tive ben­e­fit/risk op­tion for peo­ple liv­ing with the dai­ly risk and bur­den of FCS.

This is where I’ll note that FDA com­mis­sion­er Scott Got­tlieb once ad­vo­cat­ed for dis­clos­ing those CRLs, on­ly to re­nege af­ter be­ing vot­ed in as FDA com­mis­sion­er last year. Had he fol­lowed through, there wouldn’t be any ques­tions about Akcea’s po­si­tion. None of that, though, has dam­aged his pop­u­lar­i­ty with the in­dus­try, which has cheered the agency’s re­spon­sive­ness in speed­ing up re­views.

In an in­ter­nal re­view put out ahead of the pan­el re­view, though, the FDA re­view­ers spelled out the prob­lems with the ap­pli­ca­tion.

The agency re­view­ers 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?

Ev­i­dent­ly not.

Akcea has a mar­ket cap of $2.3 bil­lion, which it will need to ride out the storm. The com­pa­ny had 100 staffers at the end of the year, but was swelling fast in an­tic­i­pa­tion of an ap­proval for this and one oth­er drug. Be­fore the re­jec­tion, Akcea said it had 270 em­ploy­ees. Fri­day morn­ing, the com­pa­ny was small­er.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.