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

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

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).

How to cap­i­talise on a lean launch

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.

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The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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Mer­ck KGaA spin­out gets first fund­ing to bring dual-act­ing can­cer mol­e­cules in­to the clin­ic

Two and a half years after launch, Merck KGaA spinout iOnctura is getting its first major round of funding.

The oncology startup raised €15 million ($16.6 million) to put its lead drug into the clinic and get its second drug past IND-enabling tests. INKEF Capital and VI Partners co-led the round and were joined by the biotech’s longtime backer M Ventures, an arm of Merck KGaA, and Schroder Adveq.

Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Am­gen aug­ments Asia foothold by tak­ing over Astel­las joint ven­ture in Japan

California-based Amgen, which does the bulk of its business in the United States, made its ambition to reinvigorate its growth prospects by expanding its presence in Asia clear at the sidelines of the JP Morgan healthcare conference in San Francisco earlier this month.

The Thousand Oaks-based company on Thursday executed its plan to dissolve the joint venture with Astellas — created in 2013 — to operate the unit independently in Japan. With its rapidly aging population, the region represents an appealing market for Amgen’s osteoporosis treatments Prolia and Evenity as well as a cholesterol-lowering injection Repatha.

Daphne Zohar (PureTech)

PureTech bags $200M from sale of Karuna shares — still siz­zling from promis­ing schiz­o­phre­nia da­ta

Cashing in on the exuberance around Karuna Therapeutics and its potential blockbuster CNS drug, PureTech has sold a chunk of the biotech’s shares to Goldman Sachs for $200 million.

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