FDA or­ders Karyopharm to halt en­roll­ment for all se­linex­or tri­als, cit­ing in­com­plete safe­ty warn­ing

Late Fri­day night Karyopharm Ther­a­peu­tics $KPT alert­ed in­vestors that the FDA has slapped a par­tial hold on all stud­ies in­volv­ing its lead can­cer drug se­linex­or, halt­ing en­roll­ment for work on a drug that was re­cent­ly tapped for a 2018 fil­ing with the FDA.

Reg­u­la­tors or­dered the par­tial hold af­ter cit­ing, in writ­ing, in­com­plete in­for­ma­tion in a brochure on the drug which in­clud­ed an in­com­plete list of the ad­verse events as­so­ci­at­ed with the drug. The state­ment does not say when the agency first in­formed the com­pa­ny of the par­tial hold, but Karyopharm says that as of Fri­day the com­pa­ny has sup­plied the in­for­ma­tion re­quest­ed to get the hold lift­ed.

Say­ing you’ve re­spond­ed to the FDA at the same time you’re an­nounc­ing a par­tial hold rais­es some ques­tions on tim­ing. How long did the com­pa­ny know about the hold be­fore the alert late Fri­day?

“Karyopharm Ther­a­peu­tics re­ceived the let­ter no­ti­fy­ing the com­pa­ny of the par­tial clin­i­cal hold with­in the past week,” a com­pa­ny spokesper­son said in re­sponse to a query from me. The spokesper­son did not an­swer my query on how many days ago the no­tice ar­rived or whether reg­u­la­tors had told them ver­bal­ly ear­li­er, which is rou­tine.

The sus­pen­sions were flagged on Twit­ter Fri­day, well ahead of the news, af­ter the biotech’s shares slid 10% ahead of the close.

The New­ton, MA-based biotech added that it be­lieves the halt won’t af­fect the de­vel­op­ment time­lines al­ready of­fered. Karyopharm, led by CEO Michael Kauff­man, lists 8 dif­fer­ent clin­i­cal pro­grams for se­linex­or on its web site.

Bri­an Abra­hams at Jef­feries was hap­py to write it off as “just an ad­min­is­tra­tive blun­der.”

Af­ter speak­ing with man­age­ment, our un­der­stand­ing is that this is due to an AE (ad­verse event) ta­ble that had in­ad­ver­tent­ly been re­moved from the in­ves­ti­ga­tor’s brochure and in­formed con­sent forms used in the tri­als in a re­cent ver­sion. FDA re­quest­ed that the ta­ble be up­dat­ed and re-in­sert­ed, and KP­TI has pro­vid­ed that up­dat­ed in­for­ma­tion. Our un­der­stand­ing is that this is pure­ly an ad­min­is­tra­tive blun­der, and that there have been no new safe­ty is­sues or deaths from the drug. While this is not fa­vor­able for their cred­i­bil­i­ty re­gard­ing tri­al con­duct, we be­lieve the com­pa­ny has tak­en ac­tion to im­prove their process­es such that go­ing for­ward hu­man er­ror should not cause an­oth­er mi­nor set­back in their de­vel­op­ment pro­gram.

Karyopharm tout­ed da­ta from a sin­gle-arm study last fall demon­strat­ing a par­tial re­sponse in rough­ly 1 in 5 pa­tients out of 78 evalu­able pa­tients suf­fer­ing from drug-re­sis­tant mul­ti­ple myelo­ma. And they gained a spike in the stock price by com­par­ing that fa­vor­ably to his­tor­i­cal da­ta. The biotech planned to add an­oth­er 120 pa­tients to that study and take the da­ta to the FDA in search of an ac­cel­er­at­ed ap­proval.

Just a few days ago, though, the biotech al­so con­ced­ed that the drug failed a mid-stage study for acute myeloid leukemia. Se­linex­or works by in­hibit­ing the nu­clear ex­port pro­tein XPO1 (al­so called CRM1), trig­ger­ing cell apop­to­sis.

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.

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 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.

Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

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.

Dave Barrett, Brian Chee, Amir Nashat, Amy Schulman. Polaris

Bob Langer's first port of call — Po­laris Part­ners — maps $400M for ninth fund

Health and tech ven­ture group Po­laris Part­ners, which counts Alec­tor, Al­ny­lam and Ed­i­tas Med­i­cine as part of its port­fo­lio, is set­ting up its ninth fund, rough­ly two years af­ter it closed Po­laris VI­II with $435 mil­lion in the bank, sur­pass­ing its tar­get by $35 mil­lion.

The Boston-based firm, in an SEC fil­ing, said it in­tends to raise $400 mil­lion for the fund. Po­laris — which rou­tine­ly backs com­pa­nies mold­ed out of the work done in the lab of pro­lif­ic sci­en­tist Bob Langer of MIT  — typ­i­cal­ly in­vests ear­ly, and sticks around till com­pa­nies are in the green. Like its peers at Flag­ship and Third Rock, Po­laris is all about cham­pi­oning the lo­cal biotech scene with a steady flow of start­up cash.