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

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III VOYAGER before they give a judgment.