#ACC21: Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfiz­er and Bris­tol My­ers Squibb’s non-war­farin blood thin­ner Eliquis has raced out to be­come the most pre­scribed drug of its class on the mar­ket — even over­tak­ing war­farin’s long-time lead. But in tricky-to-treat pa­tients af­ter a valve re­place­ment, an in­ves­ti­ga­tor-spon­sored study couldn’t turn up ben­e­fit and raised a trou­bling safe­ty sig­nal.

Eliquis failed to show ben­e­fit over stan­dard of care in pre­vent­ing se­ri­ous clin­i­cal out­comes af­ter a transaor­tic valve re­place­ment (TAVR) and was linked to an “un­ex­plained sig­nal” in a sub­set of pop­u­la­tions with a high­er rate of non-CV deaths who did not need blood thin­ners apart from the surgery, ac­cord­ing to da­ta pre­sent­ed Sat­ur­day at the vir­tu­al Amer­i­can Col­lege of Car­di­ol­o­gy meet­ing.

The Pfiz­er and Bris­tol My­ers Squibb-part­nered drug did show some nu­mer­i­cal ben­e­fit in pre­vent­ing clots around the site of the TAVR with­out an in­creased risk of bleed­ing but couldn’t hit its out­comes marks. Mean­while, the re­sults in pa­tients who oth­er­wise were not prone to clot­ting were a trou­bling sign for re­searchers in the AT­LANTIS study, al­though they couldn’t de­ter­mine ex­act­ly how or whether Eliquis was tied to those non-CV deaths.

“Our re­sults do not sug­gest we can rou­tine­ly use (Eliquis) as the de­fault an­tithrom­bot­ic treat­ment af­ter suc­cess­ful TAVR,” said lead au­thor Jean-Philippe Col­let in a state­ment. “Al­though the safe­ty of (Eliquis) is the same as stan­dard care and it bet­ter pre­vents valve throm­bo­sis, we ob­served an un­ex­plained sig­nal on non-car­dio­vas­cu­lar mor­tal­i­ty among pa­tients who do not need oral an­ti­co­ag­u­la­tion.”

In pa­tients who are prone to ex­cess bleed­ing on non-vi­t­a­min K an­tag­o­nists like Eliquis, re­searchers said the drug could emerge as the treat­ment of choice post-TAVR. Ei­ther way, the un­ex­plained deaths are wor­thy of fur­ther analy­sis, they said. Re­searchers al­so posit­ed the re­sults could sim­ply be a “play of chance,” Col­let said.

The study was con­duct­ed by the Al­lies in Car­dio­vas­cu­lar Tri­als Ini­tia­tives and Or­ga­nized Net­works (AC­TION) Group and sought to test Eliquis against stan­dard-of-care VKAs or as­pirin. The study en­rolled 1,510 pa­tients at 50 cen­ters in four coun­tries who un­der­went a suc­cess­ful TAVR pro­ce­dure be­tween 2016-19.

One year af­ter the surgery, the study found no sig­nif­i­cant dif­fer­ence in the pri­ma­ry end­point, a com­pos­ite of all cause death, stroke, heart at­tack, valve throm­bo­sis, pul­monary or sys­temic em­bolism, deep vein throm­bo­sis or ma­jor bleed­ing be­tween Eliquis and SOC.  About 18% of pa­tients on Eliquis post­ed one of those events com­pared with 20.1% on SOC stan­dard care. There were al­so nu­mer­i­cal­ly high­er num­bers of sec­ondary end­points in­clud­ing death, stroke, heart at­tack or sys­temic em­bolism in the Eliquis group com­pared with con­trol.

The in­ves­ti­ga­tor-spon­sored AT­LANTIS study was a fol­low-up on J&J’s GALILEO tri­al test­ing blood thin­ner Xarel­to in pa­tients af­ter a TAVR. That study was stopped ear­ly due to ex­ces­sive bleed­ing in the Xarel­to arm. Re­searchers on AT­LANTIS said deaths in non-blood thin­ner in­di­cat­ed pa­tients were sim­i­lar to find­ings in GALILEO with­out the in­creased risk of bleed­ing.

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

In a first, Re­gen­eron's an­ti­body cock­tail re­duces deaths for a sub­group of hos­pi­tal­ized Covid-19 pa­tients

Scientists have come up with the first evidence that Regeneron’s antibody cocktail, which has so far only been authorized for the outpatient setting, may reduce deaths of hospitalized Covid-19 patients — albeit only a subset.

The combination of casirivimab and imdevimab is the subject of the latest data cut from RECOVERY, the large-scale UK-based trial testing a variety of potential treatments. In total, 9,785 patients hospitalized with Covid-19 were enrolled in this arm of the study and were randomly assigned to receive either usual care plus the intravenous combo or usual care alone.

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

New Alzheimer's drug ap­proval fall­out: Pub­lic Cit­i­zen seeks re­moval of FDA's Wood­cock, Cavaz­zoni and Dunn

As Capitol Hill begins to wake up to the financial and scientific mess behind the FDA’s approval of Biogen’s new controversial Alzheimer’s drug Aduhelm, nonprofit watchdog Public Citizen is now calling for the top three FDA officials who are responsible to be removed from their positions.

In a letter to HHS Secretary Xavier Becerra on Wednesday, the group highlighted the “litany of flaws” in the FDA’s approval of the new drug, including the “unprecedented, inappropriately close” collaboration between the FDA and Biogen in the analysis of key trial data, basing approval on an unvalidated surrogate endpoint, not following the advice of its expert advisory committee (3 members of which have since resigned), and the wide label that the agency granted.

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Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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Aus­tralian spin­out eyes the clin­ic with a pro­phy­lac­tic nasal spray for Covid-19

Whether patients are immunocompromised or just don’t like needles, one fledgling Australian biotech says it has an alternative to Covid-19 vaccines that doesn’t involve a jab in the arm — and on Tuesday, it pulled in a fresh round of funding to take it into the clinic.

ENA Respiratory, which spun out of ENA Therapeutics last year, has pulled in nearly $24.7 million (AU $30 million) to advance its nasal spray for respiratory viral infections, the company said Tuesday.

Someit Sidhu, JATT

An­oth­er life sci­ences SPAC has popped up from a small biotech CEO with the help of Take­da, No­var­tis vet­er­ans

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The SPAC train has slowed down since the extraordinarily high levels from late 2020 into early this year, but Tuesday saw the filing of a new blank-check company targeting the life sciences industry.

Jatt Acquisition submitted its SEC paperwork Tuesday, penciling in an estimated raise of $120 million as it sets its sights on a reverse merger partner. The SPAC is run by Someit Sidhu, a co-founder of Pathios Therapeutics, as well as CEO of Akaza Bioscience and Izana Bioscience. Sidhu will control about 97% of the blank-check company’s shares, per the S-1.

Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

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CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”