No­var­tis CEO Vas Narasimhan lines up his late-stage block­buster con­tenders — mix­ing old fa­vorites and add-ons

Every Big Phar­ma com­pa­ny is judged by its late-stage pipeline and the num­ber of prospec­tive block­busters in play. No­var­tis CEO Vas Narasimhan is giv­ing his piv­otal strat­e­gy top marks to­day as the gi­ant play­er re­views its de­vel­op­ment game plan in the wake of a cou­ple of key set­backs.

Adding it all up, No­var­tis is us­ing its R&D re­view to high­light a tal­ly of 26 block­busters in the pipeline, 13 projects in what is now grouped in­to cell, gene and ra­di­oli­gand work — adding ra­dio­phar­ma­ceu­ti­cals to the group — while aim­ing for 60 “ma­jor” reg­u­la­to­ry sub­mis­sions from 2019-2022. And it’s al­ready lin­ing up promised ap­provals for next year, bet­ting that they can shoot for key reg­u­la­to­ry OKs based on the da­ta in hand.

The move to ease con­cerns about the com­pa­ny’s fu­ture rev­enues comes af­ter No­var­tis re­port­ed that the FDA had re­ject­ed its big ap­pli­ca­tion to sell canakinum­ab for heart dis­ease, wip­ing out one of their ear­li­er boasts, with a de­ci­sion on the gener­ics side of the busi­ness to throw in the tow­el on a Rit­ux­an copy­cat rather than try to make a mark as a run­ner-up in that heav­i­ly con­test­ed field.

Of all the Big Phar­ma play­ers, No­var­tis has been one of the least re­luc­tant to pro­mote the scale of its in-house work, with lots of big num­bers when it comes to fu­ture op­por­tu­ni­ties for drugs that can earn $1 bil­lion or more per year. Even in late-stage de­vel­op­ment, though, the odds of suc­cess can be daunt­ing — and No­var­tis will find plen­ty of chal­lenges in get­ting these drugs to mar­ket.

Keep in mind, No­var­tis is one of the top spenders in R&D, with a bud­get of close to $9 bil­lion last year — just be­hind Roche and Mer­ck. And that rais­es the bar con­sid­er­ably on their per­for­mance in an era of steadi­ly dwin­dling ROI for the top com­pa­nies in drug de­vel­op­ment.

Here are the top drugs now spot­light­ed in late-stage de­vel­op­ment at No­var­tis:

  • AVXS101, which No­var­tis says should be good to go for a mar­ket­ing ap­proval in H1 of next year. Back in April, Narasimhan made his biggest bet yet with his $8.7 bil­lion deal to buy AveX­is and ex­pand the com­pa­ny’s pro­file in gene ther­a­py. It was a bold move, and there are plen­ty of great ex­pec­ta­tions on the line af­ter this pro­gram de­liv­ered some im­pres­sive re­sults for spinal mus­cu­lar at­ro­phy. This could be a big headache for Bio­gen, which has been rack­ing up big sales for its SMA drug Spin­raza — which al­so high­lights No­var­tis’ op­por­tu­ni­ty.
  • Mayzent (sipon­i­mod) should launch in Q1 for mul­ti­ple scle­ro­sis, says No­var­tis. Com­pa­ny of­fi­cials de­scribed this drug’s lat­est re­sults as “pret­ty much the first and on­ly study in sec­ondary pro­gres­sive MS that showed mean­ing­ful re­sults.” No­var­tis needs this one bad­ly as its $3.2 bil­lion fran­chise for Gilenya is about to get hit. An­a­lysts have of­fered a $3 bil­lion peak sales pro­jec­tion to help out.
  • Arz­er­ra — OMB157 (ofa­tu­mum­ab) — has caused plen­ty of headaches for No­var­tis this year. They were forced to pull it off the mar­ket out­side the US as com­pe­ti­tion heat­ed up for the leukemia drug. No­var­tis thinks it can re­pur­pose this drug, though, for MS, call­ing it a “next gen­er­a­tion B-cell de­ple­tor with a po­ten­tial­ly fa­vor­able safe­ty pro­file from faster b-cell re­ple­tion and pre­served im­mu­ni­ty, and with a con­ve­nient month­ly sub-cu­ta­neous dos­ing.”  
  • No­var­tis has a CRTh2 re­cep­tor an­tag­o­nist for mod­er­ate to se­vere asth­ma called QAW039 (fe­vip­iprant) which is be­ing lined up for a pitch. No­var­tis has in­sist­ed for years this oral ther­a­py is a po­ten­tial block­buster, but it hasn’t been in the spot­light as much as you might ex­pect for a would-be top con­tender.
  • RTH258 (brolu­cizum­ab) is slat­ed to be the big Re­gen­eron ri­val to Eylea that can slice away a chunk of the block­buster fran­chise with an eas­i­er dos­ing reg­i­men. It’s been a top con­tender at No­var­tis for some time, but an­a­lysts have be­gun to raise doubts as Re­gen­eron came on with its own new dos­ing strat­e­gy and Roche jumped in as well with its own con­tender, faricimab, which has 16-week da­ta to boast about.
  • No­var­tis has had plen­ty of is­sues with be­ing a lit­tle lat­er to the game than planned, and that has been on dis­play with its sick­le cell dis­ease drug SEG101 (crizan­l­izum­ab). The ther­a­py has demon­strat­ed a dou­bling of the re­sponse rate over place­bo in pre­vent­ing a painful va­so-oc­clu­sive cri­sis for pa­tients. But af­ter ini­tial­ly ink­ing in a 2018 fil­ing time­line, No­var­tis has shift­ed back to 2019.
  • Just a cou­ple of weeks ago No­var­tis ac­knowl­edged that reg­u­la­tors had bat­ted back its ap­pli­ca­tion to mar­ket ACZ885 (canakinum­ab) for car­dio risk re­duc­tion, but com­pa­ny ex­ecs im­me­di­ate­ly piv­ot­ed to their work in can­cer, with 3 Phase lll tri­als in ad­ju­vant NSCLC, 1st line NSCLC, and 2nd line NSCLC. No­var­tis says it has a shot at be­com­ing the “stan­dard of care in these set­tings,” but they of­ten hype prospects.

Not all of these drugs will make it, but they do help raise the bar for R&D per­for­mance in this sec­tor as oth­er Big Phar­ma ri­vals an­gle in with their own de­vel­op­ment strate­gies. No­var­tis has al­so shown that it’s ca­pa­ble of sur­prise, so don’t ex­pect this tal­ly to re­main sta­t­ic through 2019.

Im­age: Vas Narasimhan. AP IM­AGES

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.
The oral TKI, designed to zero in on HER2 with a bonus for penetrating the blood brain barrier, delivered a 46% hazard ratio — reduction in risk of disease progression or death — when combined with Herceptin and Xeloda compared to the branded combo alone. That was the primary endpoint. And then two key secondaries followed, starting with a 34% reduction in risk of death alone with a p value for overall survival that hit an approval worthy p=0.0048. There was a more dramatic 52% HR among almost half of the patients who had a brain metastasis at the time of the trial, which some of the analysts see as a key to market success.
We’ll have to wait until the San Antonio Breast Cancer Symposium for the breakdown on just how many months of PFS and OS Seattle Genetics is talking about.
While the researchers were after drug resistant third-line cases in the study, where regulators are generous in allowing high levels of toxicity for dying patients, the safety profile is still key here to the drug’s competitive position on the market. By steering clear of EGFR-linked toxicity, the company is looking for a better safety profile. And while the triplet led to a 5.7% drop out rate due to adverse events, compared to 3% for the double, analysts have been scoring this one much better than Nerlynx or Tykerb.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

FDA ap­proval lets Foamix set its maid­en ac­ne ther­a­py on course for US mar­ket launch

Months ago, Foamix leaned on its biggest shareholders — Perceptive Advisors and OrbiMed — to financially grease its wheels, ahead of the FDA decision date for its acne therapy. On Friday, that approval came in — and the topical formulation of the antibiotic minocycline is set for a January launch.

The therapy, Amzeeq (formerly known as FMX101), was approved to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients aged 9 and older.

Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Christine Bunt, Robert Langer. Verseau

Armed with Langer tech and $50M, Verseau hails new check­point drugs un­leash­ing macrophages against can­cer

The rising popularity of CD47 has propelled the “don’t-eat-me” signal to household name status in the immuno-oncology world: By blocking that protein, the theory goes, one can stop cancer cells from fooling macrophages. But just as PD-(L)1 merely represents the most fruitful of all checkpoints regulating T cells, Verseau Therapeutics is convinced that CD47 is one of many regulators one can modulate to stir up or tame the immune system.

Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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