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

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.

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.

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.

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.

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.

→  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.”