Pascal Soriot, AstraZeneca CEO (AP Images)

#ACC21: As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

As­traZeneca hasn’t seen many set­backs in re­cent months for SGLT2 in­hibitor Farx­i­ga, which broke ground in heart fail­ure and kid­ney dis­ease re­gard­less of di­a­betes di­ag­no­sis. But the British drug­mak­er had to ad­mit de­feat in tak­ing Farx­i­ga in­to Covid-19. How­ev­er, fol­low-up re­sults add a bit of a sil­ver lin­ing to that tri­al’s safe­ty da­ta.

Of hos­pi­tal­ized Covid-19 pa­tients dosed with As­traZeneca’s Farx­i­ga, 11.2% ex­pe­ri­enced an or­gan fail­ure or died af­ter 30 days of ther­a­py com­pared with 13.8% of those giv­en place­bo, ac­cord­ing to fol­low-up da­ta from the DARE-19 study re­vealed Sun­day at the vir­tu­al Amer­i­can Col­lege of Car­di­ol­o­gy meet­ing.

It’s a bad miss in a high-risk pop­u­la­tion for Farx­i­ga, an SGLT2 in­hibitor that re­cent­ly won ap­provals in heart fail­ure and kid­ney dis­ease re­gard­less of a di­a­betes di­ag­no­sis. As­traZeneca re­leased topline da­ta from that Phase III study back in April, ap­par­ent­ly putting an end to Farx­i­ga’s quest against Covid-19.

Re­searchers point­ed out that on all or­gan fail­ure events — in­clud­ing lung, heart or kid­ney — or death, Farx­i­ga post­ed re­sults that were “di­rec­tion­al­ly fa­vor­able” over place­bo but not at a sig­nif­i­cant lev­el. Mikhail Kosi­borod, the study’s lead re­searcher, said bet­ter clin­i­cal out­comes in the study’s 1,250 pa­tients tied to im­prov­ing stan­dard of care be­tween April 2020 and Jan­u­ary.

Mikhail Kosi­borod

“Our study gen­er­ates a hy­poth­e­sis that (Farx­i­ga) may of­fer or­gan pro­tec­tion in acute­ly ill pa­tients who are hos­pi­tal­ized with COVID-19, but we were not able to prove this be­yond a rea­son­able doubt be­cause pa­tient out­comes rapid­ly im­proved dur­ing the study pe­ri­od, mak­ing it much hard­er to ac­crue enough events and reach sta­tis­ti­cal cer­tain­ty,” Kosi­borod said in a state­ment.

De­spite the fail, what As­traZeneca is tak­ing away from the re­sults is that its SGLT2 showed a com­pa­ra­ble safe­ty pro­file to place­bo, adding more in­for­ma­tion to clin­i­cal guid­ance for high-risk pa­tients who are al­so tak­ing an SGLT2 dur­ing Covid-19 ther­a­py.

Pa­tients on Farx­i­ga post­ed nu­mer­i­cal­ly few­er se­ri­ous side ef­fects than place­bo in DARE-19 with two non-se­vere cas­es of di­a­bet­ic ke­toaci­do­sis ob­served, both in the Farx­i­ga arm and in pa­tients with pri­or his­to­ry of type 2 di­a­betes.

“Our study opens the door to ask­ing ad­di­tion­al ques­tions,” Kosi­borod said. “The idea for DARE-19 was quite un­ortho­dox when we start­ed — every­one was con­cen­trat­ing on an­tivi­rals and an­ti-in­flam­ma­to­ry drugs, so it is fas­ci­nat­ing to hy­poth­e­size that SGLT2 in­hibitors may pro­vide or­gan pro­tec­tion in acute ill­ness. This should in­form fu­ture clin­i­cal sci­ence and hope­ful­ly lead to fur­ther in­ves­ti­ga­tions.”

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).

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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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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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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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.”

Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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Geoffrey Porges, SVB Leerink

Top an­a­lyst maps a rocky road for Ver­tex — un­less they adopt a $10B M&A cam­paign to save the pipeline

After repeatedly poking Vertex $VRTX execs with pointed criticism of their R&D strategy, top SVB Leerink analyst Geoffrey Porges is now turning up the heat to a full-scale roasting.

In a note out early Monday morning, Porges spotlights the impact of Vertex’s recent follow-up failure on AATD — their treatment hit the endpoint but missed on commercial prospects — rewriting his recommended scenario for CEO Reshma Kewalramani as she grapples with the setback.

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