No­var­tis lays out block­buster launch­es for 2018-2020, with sur­pris­ing in­clu­sion of Kym­ri­ah

As No­var­tis shakes off its Al­con eye busi­ness and the loss of two high-pro­file ex­ec­u­tives, chief Vas Narasimhan has out­lined the Swiss drug­mak­er’s ros­ter of 14 block­buster launch­es, a bulk of which are ex­pect­ed to win ap­proval be­tween this year and 2020. The drugs in­clud­ed in the list are large­ly fa­mil­iar, but the in­clu­sion of the com­pa­ny’s pi­o­neer­ing CAR-T ther­a­py Kym­ri­ah, whose adop­tion has been wob­bly due to man­u­fac­tur­ing woes, will raise some eye­brows.

In 2017, No­var­tis spent a hefty $9 bil­lion on R&D, mak­ing it one of the top spenders in glob­al bio­phar­ma. In­vestors ex­pect to see the com­pa­ny to now get bang for its buck. Last No­vem­ber, the com­pa­ny used it R&D re­view to high­light 26 block­buster con­tenders in its ar­se­nal and of­fer a rosy pic­ture of things to come af­ter suf­fer­ing a few knocks — the FDA re­ject­ing its heart drug, and the com­pa­ny aban­don­ing its at­tempt at a Rit­ux­an copy­cat.

Since then, the com­pa­ny has seen good days and bad. On the pos­i­tive front, its gene ther­a­py for SMA se­cured the FDA’s pri­or­i­ty re­view, and its sick­le cell drug won break­through ther­a­py sta­tus. The drug­mak­er al­so swal­lowed a cell and gene ther­a­py man­u­fac­tur­er in an at­tempt to un­clog the com­mer­cial roll­out for Kym­ri­ah. In a first for a multi­na­tion­al phar­ma­ceu­ti­cal com­pa­ny, No­var­tis’ San­doz unit tied up with Cana­di­an med­ical cannabis pro­duc­er Tilray, a land­mark en­dorse­ment of the con­tro­ver­sial plant. On Wednes­day, as part of its full-year 2018 re­sults, the drug­mak­er said four new­er prod­ucts — in­clud­ing Cosen­tyx and En­tresto — in its ros­ter of med­i­cines achieved block­buster sta­tus in 2018.

On the oth­er end of the scale, No­var­tis has al­so suf­fered a num­ber of set­backs in the last quar­ter of 2018. For in­stance, its mi­graine drug Aimovig — billed as a block­buster and part­nered with Am­gen — was re­fused en­dorse­ment by the UK’s NICE, months af­ter the agency de­clined to give the nod for Kym­ri­ah. Two top ex­ec­u­tives — CAR-T chief David Leb­wohl and on­col­o­gy head Liz Bar­rett — al­so left the drug­mak­er to take top po­si­tions in small biotechs. And J&J dealt No­var­tis a blow when its pso­ri­a­sis drug Trem­fya beat the dom­i­nant Cosen­tyx in a head-to-head study.

2018

  • AIMOVIG — The mi­graine drug forms part of a new crop of bi­o­log­ics tar­get­ing the CGRP pro­tein that trans­mits pain sig­nals in­to the brain. The drug was the first to win ap­proval in 2018, and with­in months ri­val treat­ments from Lil­ly and Te­va were al­so giv­en reg­u­la­to­ry nods. All three have demon­strat­ed sim­i­lar ef­fi­ca­cy and safe­ty in tri­als. Like its ri­vals, the drug is priced at $575 per month and has been pegged as a po­ten­tial block­buster. Fol­low­ing the NICE set­back, re­ports sug­gest­ed Aimovig was ex­clud­ed from phar­ma­cy ben­e­fits man­ag­er CVS’ for­mu­la­ry in the Unit­ed States. This will be a blow, but there are oth­er PBMs on the block.
  • KYM­RI­AH — The pi­o­neer­ing CAR-T drug was FDA ap­proved amidst great fan­fare in 2017, and since then the FDA has ex­pand­ed its use in the Unit­ed States and the EC al­so ap­proved the drug last Au­gust. NICE re­fused to en­dorse the pricey drug. Mean­while, ri­vals such as Gilead’s Yescar­ta have emerged, and Kym­ri­ah sales have suf­fered due to man­u­fac­tur­ing is­sues. In the fourth quar­ter, the drug gen­er­at­ed a pal­try $28 mil­lion. How­ev­er, No­var­tis is do­ing its best to shore up man­u­fac­tur­ing, hav­ing bought cell and gene ther­a­py man­u­fac­tur­er Cell­for­Cure.
  • LU­TATHERA — The can­cer drug, which came with No­var­tis’ $4 bil­lion ac­qui­si­tion of Ad­vanced Ac­cel­er­a­tor Ap­pli­ca­tions in 2017, paid off hand­some­ly in ear­ly 2018 af­ter the FDA gave it a quick OK. No­var­tis re­port­ed an 11% jump in on­col­o­gy rev­enue in the fourth quar­ter, dri­ven part­ly by Lu­tathera sales of $81 mil­lion.

2019

  • BYL719 — Oth­er­wise known as alpelis­ib, the PI3K in­hibitor near­ly dou­bled pro­gres­sion-free sur­vival in a third of pa­tients with a hard-to treat form of breast can­cer last Oc­to­ber. Oth­er drugs in this class, in­clud­ing Roche’s taselis­ib, have large­ly crashed and burned due to safe­ty con­cerns.
  • MAYZENT — Ex­pect­ed to launch this year, the MS drug al­so known as sipon­i­mod is crit­i­cal for the com­pa­ny as one of its top sell­ers Gilenya has gener­ic com­pe­ti­tion loom­ing. Com­pa­ny of­fi­cials have pre­vi­ous­ly de­scribed the drug’s da­ta in glow­ing terms, and an­a­lysts have con­curred, of­fer­ing a $3 bil­lion peak sales pro­jec­tion for the treat­ment.
  • RTH258 — The eye drug has been built up as a ri­val to Re­gen­eron’s flag­ship block­buster in­jec­tion Eylea and CEO Narasimhan has gone so far as to say RTH258 is “con­sis­tent­ly su­pe­ri­or” to Eylea, af­ter con­duct­ing ret­ro­spec­tive analy­ses of late-stage da­ta last year. Eylea has been un­touch­able for more than a decade, so it is up to No­var­tis to prove oth­er­wise.
  • ZOL­GENS­MA — The gene ther­a­py is cur­rent­ly un­der FDA re­view and the agency is ex­pect­ed to an­nounce its de­ci­sion in May. In its re­view post­ed in De­cem­ber, ICER sug­gest­ed the Zol­gens­ma — with a list price of $2 mil­lion — would of­fer more cost-ef­fec­tive ben­e­fit in the long run ver­sus ri­val Bio­gen’s Spin­raza. How­ev­er, the Swiss drug­mak­er has sug­gest­ed a price of $4 mil­lion for the cu­ra­tive ther­a­py, which it ac­quired via a $8.7 bil­lion takeover of AveX­is, may be jus­ti­fied.

2020

  • COSEN­TYX — The pso­ri­a­sis drug that be­came a block­buster in 2016 is one of No­var­tis’ key drugs, and the drug­mak­er is work­ing on ex­pand­ing the IL-17A in­hibitor’s mar­ket by in­clud­ing pa­tients with pso­ri­at­ic arthri­tis, anky­los­ing spondyli­tis and non-ra­di­ograph­ic ax­i­al spondy­larthri­tis (nrAxS­pA). Piv­otal da­ta are ex­pect­ed lat­er this year and, if pos­i­tive, will be fol­lowed by a mar­ket­ing ap­pli­ca­tion be­fore the end of this year.
  • EN­TRESTO — The med­i­cine is an­oth­er top sell­er for No­var­tis and is cur­rent­ly ap­proved for HFrEF (for­mer­ly known as sys­tolic heart fail­ure) — in these pa­tients the heart mus­cle does not con­tract ef­fec­tive­ly, re­duc­ing the lev­el of oxy­gen-rich blood pumped in­to to the body. Ini­tial­ly a slow mov­ing prod­uct ham­pered by physi­cians re­luc­tant to adopt a new ther­a­py and in­sur­ers who balked at its price, En­tresto is now com­fort­ably a block­buster prod­uct. The drug is now un­der eval­u­a­tion for HF­pEF (al­so re­ferred to as di­as­tolic heart fail­ure) — a now larg­er group of pa­tients whose heart mus­cle con­tract nor­mal­ly but ven­tri­cles do not re­lax as they should dur­ing ven­tric­u­lar fill­ing. Da­ta from the tri­al PARAGON-HF are ex­pect­ed in the third quar­ter of 2019.
  • INC280 — Oth­er­wise known as cap­ma­tinib, the MET in­hibitor was li­censed to No­var­tis from In­cyte in 2009. Mid-stage da­ta on the drug in cer­tain pa­tients with the most com­mon form of lung can­cer (NSCLC), pre­sent­ed last Oc­to­ber, showed INC280 in­duced an ORR of 72% in treat­ment-naive pa­tients and about 39% in pre­vi­ous­ly treat­ed pa­tients. No­var­tis is ex­pect­ed to sub­mit a mar­ket­ing ap­pli­ca­tion lat­er this year.
  • OMB157 — Oth­er than the ap­proved Gilenya and Mayzent — which is cur­rent­ly un­der re­view — ofa­tu­mum­ab (OMB157) is an­oth­er drug No­var­tis is hop­ing to use in MS. The drug, al­ready sold as Arz­er­ra, has caused a num­ber of prob­lems for No­var­tis as a treat­ment for leukemia — the drug­mak­er was forced to pull it off the mar­ket out­side the US as com­pe­ti­tion heat­ed up. No­var­tis thinks it can re­pur­pose the drug for MS, an in­di­ca­tion for which it is cur­rent­ly be­ing in­ves­ti­gat­ed in two Phase III stud­ies.
  • PDR001 COM­BO — PDR001, al­so called spar­tal­izum­ab, is No­var­tis’ PD-1 in­hibitor and is be­ing test­ed in a num­ber of can­cers. A late-stage study test­ing the drug in com­bi­na­tion with No­var­tis’ ap­proved can­cer drugs — Tafin­lar and Mekin­ist — in pa­tients with metasta­t­ic melanoma is on­go­ing.
  • QVM149 — The asth­ma drug is cur­rent­ly be­ing test­ed against stan­dard triple com­bi­na­tion ther­a­py in a late-stage study in un­con­trolled asth­mat­ics — the tri­al is ex­pect­ed to be com­plet­ed this year.
  • SEG101 — Ex­pect­ed to launch in 2020, the sick­le cell dis­ease drug has se­cured the FDA’s break­through ther­a­py des­ig­na­tion ear­li­er this month. Af­ter a de­lay in 2018, a mar­ket­ing ap­pli­ca­tion for the drug is ex­pect­ed this year.

Im­age: NO­VAR­TIS

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.”