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

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Vir's CMO says he's sur­prised that a low dose of their he­pati­tis B drug ap­pears promis­ing in ear­ly slice of da­ta — shares soar

Initial topline data from a Phase I study of a new therapeutic for chronic hepatitis B virus was so promising that it surprised even the CMO of the company that produces it.

Vir Biotechnology on Tuesday announced that its VIR-3434 molecule reduced the level of virus surface antigens present in a blinded patient cohort after eight days of the trial with just a single 6 mg dose. Six of the eight patients in the cohort were given the molecule, and the other two a placebo—all six who received the molecule saw a mean antigen reduction of 1.3 log10 IU/mL, Vir said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

David Marek, Myovant

My­ovant beefs up da­ta pack­age in NDA #3, boost­ing its case for longterm dos­ing of Pfiz­er-part­nered re­l­u­golix

When Pfizer handed over $650 million in cash to partner on Myovant’s relugolix, the pharma giant made clear that the deal — valued at $4.2 billion total — was just as much about the approved indication of prostate cancer as the two women’s health conditions the drug could treat.

A month later, the two companies are offering another glimpse of the therapy’s longterm potential in endometriosis.

Look­ing to win over some skep­ti­cal an­a­lysts, Rhythm beats the drum on in­ter­im da­ta in PhII bas­ket study for ad­di­tion­al in­di­ca­tions

Rhythm Pharmaceuticals has been working toward expanding the FDA approval they received just two months ago for three rare genetic disorders that result in obesity. In December, their Phase III cut of data saw mixed reactions from analysts, but new interim results released Tuesday may provide more excitement.

In an ongoing Phase II study for setmelanotide across individuals with one of three distinct rare genetic diseases of obesity, 65 patients had reached the Dec. 17 cutoff date for evaluation. Among patients who met the primary endpoint of at least 5% weight loss over three months, Rhythm saw an average reduction of no less than 7.1% in any of the groups.

Eli Lil­ly demon­strates that 2 an­ti­bod­ies beat 1 for guard­ing against se­vere Covid-19. But can that solve the first an­ti­body’s prob­lem amid slow up­take?

It seems safe to say that two antibodies are better than one.

Eli Lilly released the largest results yet on Tuesday for their Covid-19 neutralizing antibody cocktail, announcing that the combo reduced deaths and hospitalizations in coronavirus patients by 70%. Across 1,000 patients, there were 11 such events in the treatment group and 36 in the placebo group.

The breakdown for deaths alone was even starker: 10 in the placebo group and 0 in the treatment group. Lilly added that the drug hit secondary endpoints for reducing viral load and alleviating symptoms, although they did not disclose numbers.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.