No­var­tis team scores a pi­o­neer­ing first in car­dio R&D. But can they sell it?

No­var­tis is fac­ing an­oth­er block­buster chal­lenge of glob­al pro­por­tions.

How do you mar­ket a heart drug with re­al but clear­ly lim­it­ed health ben­e­fits? One where there’s no es­tab­lished abil­i­ty to se­ri­ous­ly cut down the rate of death — and head­ed to a field where pay­ers are skilled at stand­ing be­tween pa­tients and high-cost PC­SK9 drugs?

That’s the sit­u­a­tion for No­var­tis as it takes its da­ta on canakinum­ab to the FDA and reg­u­la­tors around the world.

The phar­ma gi­ant’s achieve­ment can’t be ig­nored. This is the first time an an­ti-in­flam­ma­to­ry ther­a­py was able “to demon­strate re­duced risk of ma­jor car­dio­vas­cu­lar events,” not­ed No­var­tis CMO Vas Narasimhan in a call with re­porters ahead of their pre­sen­ta­tion at the Eu­ro­pean So­ci­ety of Car­di­ol­o­gy. And the com­pa­ny’s top re­searchers al­so hint­ed at one pos­si­ble mar­ket­ing strat­e­gy that might work best.

The key fig­ure No­var­tis plucked out of the end­points da­ta: a 15% re­duc­tion among 10,000 pa­tients in the risk of an­oth­er ma­jor car­dio­vas­cu­lar event like heart at­tack or stroke. There was a 10% “trend” to­ward a mor­tal­i­ty ben­e­fit, which won’t im­press pay­ers who have been set­ting a high bar on car­dio drugs, as No­var­tis al­ready knows first hand as they have made slow progress in mar­ket­ing En­tresto.

One ma­jor high­light on the sub­group analy­sis, though, could hold a key to iden­ti­fy­ing a large pa­tient pop­u­la­tion that could ben­e­fit more dis­tinct­ly. Us­ing their bio­mark­er for high-sen­si­tiv­i­ty C-re­ac­tive pro­tein, the half of pa­tients who were un­der the me­di­an re­sponse three months af­ter start­ing treat­ment in the CAN­TOS study had a 27% risk re­duc­tion for heart at­tack or stroke.

Pa­tients were fol­lowed for a me­di­an of 3.7 years for this tri­al.

Canakinum­ab war­rant­ed block­buster han­dling af­ter demon­strat­ing the po­ten­tial of a drug that aimed di­rect­ly at IL-1ß. The the­o­ry, which sparked con­sid­er­able skep­ti­cism among an­a­lysts, was that if you re­duced in­flam­ma­tion by hit­ting the tar­get, pa­tients would stand a bet­ter chance of go­ing with­out an­oth­er po­ten­tial­ly lethal re­ac­tion to their heart dis­ease.

No­var­tis al­ready sells this drug as Ilaris for rare cas­es of ju­ve­nile arthri­tis at about $200,000 a year — list price — in the US. But that fig­ure would have to be sig­nif­i­cant­ly chopped down for a broad pa­tient pop­u­la­tion, giv­en the Repatha headaches that Am­gen has had with equal­ly mod­est — but dis­tinct — re­sults for cut­ting LDL. Repatha lists at a lit­tle above $14,000 a year. En­tresto’s price is set at about $4,500.

There are al­so some ma­jor unan­swered ques­tions that could take many months or even years to clar­i­fy.

“The mod­est ab­solute clin­i­cal ben­e­fit of canakinum­ab can­not jus­ti­fy its rou­tine use in pa­tients with pre­vi­ous my­ocar­dial in­farc­tion un­til we un­der­stand more about the ef­fi­ca­cy and safe­ty trade-offs and un­less a price re­struc­tur­ing and for­mal cost-ef­fec­tive­ness eval­u­a­tion sup­ports it,” not­ed Stan­ford’s Robert Har­ring­ton in an ac­com­pa­ny­ing ed­i­to­r­i­al in the New Eng­land Jour­nal of Med­i­cine.

Ad­vo­cates, though, were quick to ap­plaud.

“It’s a gate­way to a very wide va­ri­ety of ther­a­pies that are go­ing to be de­vel­oped,” Cleve­land Clin­ic’s Steven Nis­sen told Sci­ence. “This is as big as any­thing we’ve seen in a while.”

But is it big enough to sell?

No­var­tis, though, likes a big chal­lenge, even af­ter ex­pe­ri­enc­ing sev­er­al ups and downs in the heart are­na. And it bought in­to an even big­ger chal­lenge with new da­ta to sup­port the drug’s abil­i­ty to re­duce the risk of lung can­cer.

One thing seems cer­tain. What­ev­er hap­pens to canakinum­ab, oth­er de­vel­op­ers will be look­ing to prove the longterm ben­e­fits of re­duc­ing in­flam­ma­tion. Look for more stud­ies among the play­ers who can fund this work, and the biotechs look­ing to make deals around Phase II.

Im­age: No­var­tis CMO Vas Narasimhan Get­ty

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology

ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development

CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.