#ACC21: Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Re­gen­eron scored an ear­ly ap­proval for lipid low­er­ing an­ti­body Evkeeza back in Feb­ru­ary, the drug­mak­er cracked open a new path­way to low­er ab­nor­mal­ly high cho­les­terol lev­els. Now, Re­gen­eron is chas­ing high triglyc­erides as well with some promis­ing mid-stage da­ta — but will ge­net­ic re­stric­tions lim­it the drug’s use?

Re­gen­eron’s Evkeeza (evinacum­ab) cut me­di­an triglyc­eride lev­els by more than 800 mg/dL (57%) in pa­tients with a rare dis­or­der caus­ing ab­nor­mal­ly high triglyc­eride lev­els com­pared with an over­all in­crease of 50 mg/dL (1.8%) in par­tic­i­pants on place­bo, ac­cord­ing to Phase II da­ta pre­sent­ed Sun­day at the vir­tu­al Amer­i­can Col­lege of Car­di­ol­o­gy meet­ing.

The da­ta are a promis­ing sign that Re­gen­eron’s an­ti­body can add on to its la­bel af­ter an ini­tial FDA ap­proval in a rare dis­ease caus­ing ab­nor­mal­ly high cho­les­terol, dubbed ho­mozy­gous fa­mil­ial hy­per­c­ho­les­terolemia, back in Feb­ru­ary. The drug is ap­proved as a sup­ple­ment to stan­dard-of-care LDL low­er­ing ther­a­pies such as statins.

Evkeeza’s win in Phase II looks like a promis­ing sign of its promise in front of reg­u­la­tors, but pa­tients’ ge­net­ic pro­files showed a big dis­par­i­ty in terms of the drug’s ef­fect on curb­ing triglyc­erides. In pa­tients with a dou­ble copy of cer­tain mu­ta­tions in the LPL path­way, which reg­u­lates cho­les­terol and triglyc­erides, Evkeeza “had es­sen­tial­ly no ben­e­fit,” re­searchers said. Mean­while, pa­tients with one copy of an LPL mu­ta­tion or no mu­ta­tions saw triglyc­eride re­duc­tions around 80%.

Pa­tients with no mu­ta­tions tak­en alone post­ed a mean re­duc­tion in triglyc­erides of 27.1% and a me­di­an re­duc­tion of 68.8%.

With those re­sults in mind, re­searchers think Evkeeza could prove to be an ef­fec­tive ther­a­py for se­vere hy­per­triglyc­eridemia giv­en an ap­pro­pri­ate ge­net­ic pro­file. Mean­while, pa­tients with dou­ble copies of LPL path­way mu­ta­tion will be left to look for oth­er op­tions.

“(This study) demon­strates the im­por­tance of ge­net­ic test­ing in peo­ple with se­vere hy­per­triglyc­eridemia be­cause by per­form­ing ge­net­ic test­ing you are able to tell which in­di­vid­u­als will re­spond to this ther­a­py and which are un­like­ly to re­spond,” lead au­thor Robert Rosen­son said in a state­ment.

The Phase II study en­rolled 51 pa­tients with the dis­or­der at 17 sites in four coun­tries in North Amer­i­ca and Eu­rope, ac­cord­ing to a re­lease. Re­gen­eron plans to try Evkeeza in larg­er stud­ies to de­ter­mine ef­fect across a broad­er pa­tient pool. By show­ing ear­ly ben­e­fit low­er­ing both LDL and triglyc­erides, Re­gen­eron thinks Evkeeza could have some ef­fect in dis­eases like di­a­betes and heart dis­ease char­ac­ter­ized by high lev­els of both lipids.

“By low­er­ing triglyc­erides by 60-80% and LDL cho­les­terol by 50% on top of statins and oth­er med­ica­tions, this agent has an op­por­tu­ni­ty to im­pact car­dio­vas­cu­lar dis­ease in these very high-risk in­di­vid­u­als,” Rosen­son said.

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.”