Cel­gene shak­en again af­ter the FDA kicks back their mar­ket­ing ap­pli­ca­tion on block­buster hope­ful ozan­i­mod

Cel­gene has been slammed with a refuse-to-file let­ter from the FDA for ozan­i­mod, the biggest late-stage drug it has in the pipeline.

The biotech re­port­ed af­ter the mar­ket closed Tues­day that the RTF came through be­cause the FDA de­ter­mined “that the non­clin­i­cal and clin­i­cal phar­ma­col­o­gy sec­tions in the NDA were in­suf­fi­cient to per­mit a com­plete re­view” for mul­ti­ple scle­ro­sis.

That’s go­ing to hurt — bad.

Cel­gene piv­ot­ed to ozan­i­mod as its pri­ma­ry Phase III block­buster hope­ful, ob­tained in their $7.2 bil­lion Re­cep­tos buy­out, af­ter its $710 mil­lion cash roll of the dice on the in­flam­ma­to­ry bow­el dis­ease drug mon­gersen (GED-301) came up snake eyes in Phase III last fall. Cel­gene has said ozan­i­mod is worth $4 bil­lion to $6 bil­lion a year in peak sales, but that’s be­com­ing an in­creas­ing­ly tough pitch with an­a­lysts.

An RTF is not the kiss of death for ozan­i­mod, but at the very least it de­lays any launch and forces CEO Mark Alles to ex­plain how they man­aged to fum­ble the ball again. For Cel­gene, it’s an un­ac­cus­tomed po­si­tion, rais­ing doubts about the com­pa­ny’s fu­ture. Notes Baird’s Bri­an Sko­r­ney:

With so many re­cent mis­steps and Revlim­id IP still a big risk amidst mul­ti­ple Para­graph IV chal­lenges, in­vestors are hes­i­tant to get back in­to what was once biotech’s poster child for con­tin­ued growth and sol­id ex­e­cu­tion.

Leerink’s Ge­of­frey Porges took a look and came up with some dis­com­fort­ing con­clu­sions about Cel­gene. His the­o­ry about what went wrong:

This on­ly adds to in­vestors’ grow­ing un­ease with the com­pa­ny’s di­rec­tion and over­sight of key ac­tiv­i­ties – in this case the com­pa­ny clear­ly made a de­ci­sion to file this ap­pli­ca­tion at risk, de­spite late in­for­ma­tion that might have been more thor­ough­ly dis­closed and ex­plored in the ap­pli­ca­tion, had the fil­ing been post­poned by a few months. The spe­cif­ic rea­sons for the RTF have not been com­plete­ly ex­plained, but Cel­gene’s com­ments sug­gest that a Cel­gene-con­duct­ed small PK/PD study for Ozan­i­mod that was com­plet­ed late last year and showed some anom­alies (ex­po­sure or PK vari­ances) which, when com­bined with the known safe­ty li­a­bil­i­ties of the S1P class, prob­a­bly trig­gered the FDA to re­quest more com­plete dis­clo­sure of this sup­ple­men­tal da­ta, and po­ten­tial­ly fur­ther ex­plo­ration of these vari­ances.

The biotech post­ed pos­i­tive Phase III da­ta on ozan­i­mod late in Oc­to­ber, in­clud­ing some fa­vor­able com­par­isons with Avonex. But there were some holes in the pre­sen­ta­tion. As not­ed last sum­mer, Cel­gene’s drug did not demon­strate a dis­abil­i­ty ben­e­fit over Avonex on a pooled ba­sis, which will like­ly blunt its com­mer­cial prospects. In­ves­ti­ga­tors re­cruit­ed 1,346 pa­tients for the SUN­BEAM tri­al, post­ing sta­tis­ti­cal­ly sig­nif­i­cant scores for the an­nu­al­ized re­lapse rate. But in a pooled analy­sis of SUN­BEAM and RA­DI­ANCE Part B stud­ies, their drug did not hit the goal for the time to 3-month con­firmed dis­abil­i­ty pro­gres­sion.

Jay Back­strom

The plan now is to get in front of the FDA AS­AP and see what they need to do to get this drug back in­to the sys­tem and hope­ful­ly point­ed to an ap­proval.

Cel­gene spooked the mar­ket re­cent­ly with some shaky fi­nan­cials, but man­aged to calm the wa­ters with its buy­out of Juno and the prospect of be­com­ing a leader in CAR-T ther­a­pies. Its set­back to­day will not sit well with in­vestors, who swift­ly drove down Cel­gene’s shares by 6.8%.

“We re­main con­fi­dent in ozan­i­mod’s clin­i­cal pro­file demon­strat­ed in the piv­otal pro­gram in re­laps­ing forms of mul­ti­ple scle­ro­sis,” said Jay Back­strom, the CMO and head of Glob­al Reg­u­la­to­ry Af­fairs for Cel­gene. “We will work with the FDA to ex­pe­di­tious­ly ad­dress all out­stand­ing items and bring this im­por­tant med­i­cine to pa­tients.”

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.

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.”

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.

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.