Once scored as a po­ten­tial block­buster, No­var­tis’ sere­lax­in fiz­zles in crit­i­cal car­dio out­comes test

Vas­ant Narasimhan

You can scratch sere­lax­in off No­var­tis’ list of po­ten­tial block­busters in the late-stage pipeline.

This morn­ing the phar­ma gi­ant said that its 4-year study of the heart drug flubbed the pri­ma­ry end­point, fail­ing to sig­nif­i­cant­ly cut the rate of car­dio­vas­cu­lar death or re­duce wors­en­ing heart fail­ure among pa­tients with acute heart fail­ure.

No­var­tis Chief Med­ical Of­fi­cer Vas Narasimhan said that the phar­ma gi­ant will con­tin­ue to look over the da­ta to de­ter­mine next steps. But the R&D jour­ney would ap­pear to be over.

De­spite win­ning one of the first break­through drug des­ig­na­tions at the FDA for this pro­gram, an FDA pan­el wasn’t per­suad­ed by the da­ta that No­var­tis of­fered. The agency for­mal­ly re­ject­ed the drug in the spring of 2014, look­ing for the out­comes da­ta from the 6,600 pa­tients re­cruit­ed for RE­LAX-AHF-2.

The EU fol­lowed up soon af­ter with a thumbs down as well.

No­var­tis ex­ecs had been con­vinced that sere­lax­in would be the next big thing in heart drugs, set on a course to block­buster sta­tus. The da­ta, how­ev­er, wouldn’t co­op­er­ate with their plans. And Leerink’s Sea­mus Fer­nan­dez was ready with last rites:

Giv­en the post-hoc na­ture of the pre­vi­ous analy­ses, rel­a­tive­ly small num­ber of clin­i­cal events, and lack of his­tor­i­cal suc­cess for oth­er agents in large acute HF tri­als, we had pre­vi­ous­ly been cau­tious on the chances for a fa­vor­able ben­e­fit on mor­tal­i­ty out­comes. Ac­cord­ing to pre­vi­ous dis­cus­sions with MEDA­Corp KOLs, suc­cess in this tri­al would have cre­at­ed a strong eth­i­cal man­date for use; how­ev­er we be­lieve the fail­ure es­sen­tial­ly ter­mi­nates all en­thu­si­asm for the drug.

The lat­est and per­haps last set­back on this drug leaves No­var­tis’ car­dio di­vi­sion de­pen­dent on En­tresto for its fu­ture. That drug has jumped off to a slow start, though, leav­ing an­a­lysts scratch­ing their heads over the drug’s po­ten­tial earn­ings.

En­tresto earned just $170 mil­lion last year, de­spite the com­pa­ny’s com­mit­ment to pay-for-per­for­mance con­tracts and a re­lent­less ef­fort to build the da­ta and pay­er deals need­ed to make the drug a suc­cess. Pay­ers, though, have their own ideas on how to han­dle a drug like this. They erect­ed bar­ri­ers with high co-pays and pri­or au­tho­riza­tion de­mands that made the drug hard to get. As Am­gen and the Re­gen­eron/Sanofi team found out the hard way with PC­SK9 drugs, try­ing to mar­ket a new drug aimed at heart dis­ease can be a dev­il­ish­ly dif­fi­cult task.

That kind of re­sis­tance will make it in­creas­ing­ly hard for large play­ers to tack­le the big and ex­pen­sive late-stage ef­forts that are need­ed to get these drugs across the fin­ish line. Sere­lax­in may ul­ti­mate­ly ex­er­cise ex­act­ly the op­po­site kind of in­flu­ence that No­var­tis was look­ing for.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

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With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

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Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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Pur­due Phar­ma pleads guilty in fed­er­al Oxy­Con­tin probe, for­mal­ly rec­og­niz­ing it played a part in the opi­oid cri­sis

Purdue Pharma, the producer of the prescription painkiller OxyContin, admitted Tuesday that, yes, it did contribute to America’s opioid epidemic.

The drugmaker formally pleaded guilty to three criminal charges, the AP reported, including getting in the way of the DEA’s efforts to combat the crisis, failing to prevent the painkillers from ending up on the black market and encouraging doctors to write more painkiller prescriptions through two methods: paying them in a speakers program and directing a medical records company to send them certain patient information. Purdue’s plea deal calls for $8.3 billion in criminal fines and penalties, but the company is only liable for a fraction of that total — $225 million.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

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An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

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