Am­gen hit with a set­back as Kypro­lis fails a key front­line tri­al for mul­ti­ple myelo­ma

Sean Harp­er, Ex­ec­u­tive Vice Pres­i­dent, Re­search and De­vel­op­ment

Am­gen re­port­ed ear­ly Tues­day that Kypro­lis has failed a Phase III tri­al for front­line use against mul­ti­ple myelo­ma, a set­back that can on­ly fur­ther sharp­en the dis­ap­point­ment an­a­lysts have felt for this ther­a­py in light of weak sales.

In­ves­ti­ga­tors say that Kypro­lis com­bined with mel­pha­lan and pred­nisone es­sen­tial­ly matched a triple com­bo us­ing Take­da’s Vel­cade. The PFS for Kypro­lis was 22.3 months com­pared to 22.1 months for the Vel­cade arm.

Am­gen’s shares slid 2.3% in pre-mar­ket trad­ing Tues­day.

The over­all sur­vival da­ta have yet to ma­ture for a read out, ac­cord­ing to Am­gen. But the big biotech didn’t have any­thing pos­i­tive to re­port this morn­ing.

Am­gen had been hop­ing to use this study to help jus­ti­fy the $10.4 bil­lion ac­qui­si­tion of Onyx Phar­ma­ceu­ti­cals back in 2013, af­ter Onyx had pushed the treat­ment through to an ap­proval. Last year, Am­gen had been bull­ish about its prospects in the blood can­cer field af­ter Kypro­lis proved more ef­fec­tive in help­ing mul­ti­ple myelo­ma pa­tients who had failed at least one pri­or treat­ment com­pared to Vel­cade. And it fol­lowed up with a new ap­proval for use against re­lapsed mul­ti­ple myelo­ma in com­bi­na­tion with Vel­cade.

Front­line use, though, would have opened up a ma­jor mar­ket op­por­tu­ni­ty to Am­gen that the com­pa­ny bad­ly need­ed. Kypro­lis earned $512 mil­lion last year, up 55% from the year be­fore. But you’ll find it at the tail end of the drugs Am­gen re­ports on, leav­ing the big biotech look­ing for new ways to add rev­enue. Vel­cade, mean­while, brings in block­buster cash for Take­da, earn­ing more than $2.5 bil­lion a year.

Cel­gene is the leader in mul­ti­ple myelo­ma, though, dom­i­nat­ing the field with Revlim­id and Po­m­a­lyst while J&J and Bris­tol-My­ers Squibb have jumped in with Darza­lex and Em­plic­i­ti.

Look­ing over the field and weigh­ing the set­back at Am­gen, Leerink’s Ge­of­frey Porges con­clud­ed that gener­ic Vel­cade will be the dom­i­nant drug in use. He con­clud­ed:

“With the mul­ti­ple myelo­ma field search­ing for the op­ti­mum com­bi­na­tion treat­ment com­bi­na­tion it seems like­ly that soon-to-be-gener­ic Vel­cade will be the pro­tea­some in­hibitor of choice in front line pa­tients with the back­bone of J&J’s (JNJ, [OP]) Darza­lex (dara­tu­mum­ab)‎, Cel­gene’s (CELG, [MP]) Revlim­id (lenalido­mide), and dex­am­etha­sone (aka Darza­lex/ Rev/ Dex). Vel­cade’s patent is set to ex­pire in 2017. A num­ber of Kypro­lis stud­ies are still on­go­ing – and we are cau­tious about the out­comes. These tri­als in­clude AR­ROW, a phase 3 tri­al of Kypro­lis (with dex) re­lapsed and re­frac­to­ry MM, set to read-out mid- 2017; a phase 3 com­par­ing Kypro­lis vs. Vel­cade (both with rev/ dex) in new­ly di­ag­nosed MM, set to read-out 2H 2017; and the over­all sur­vival da­ta of phase 3 EN­DEAV­OR study of Kypro­lis vs. Vel­cade (both with dex) in re­lapsed MM ex­pect­ed 2018.”

Said R&D chief Sean Harp­er:

“The CLAR­I­ON re­sults, gen­er­at­ed in the con­text of a mel­pha­lan-con­tain­ing reg­i­men, are dis­ap­point­ing, es­pe­cial­ly giv­en the ro­bust da­ta we’ve seen in the sec­ond-line set­ting. How­ev­er, the myelo­ma land­scape has changed dra­mat­i­cal­ly since the de­sign of the CLAR­I­ON study with very few new­ly di­ag­nosed pa­tients treat­ed with mel­pha­lan-based reg­i­mens, par­tic­u­lar­ly in the U.S.  We re­main com­mit­ted to ex­plor­ing Kypro­lis in com­bi­na­tion with oth­er agents to ad­vance the treat­ment of mul­ti­ple myelo­ma.”


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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Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.

UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.

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.”