As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA re­cent­ly spurned an ap­pli­ca­tion to al­low As­traZeneca’s block­buster drug Farx­i­ga for type 1 di­a­betes that can­not be con­trolled by in­sulin, cit­ing safe­ty con­cerns — the US reg­u­la­tor has en­dorsed the use of the SGLT2 treat­ment to re­duce the risk of hos­pi­tal­i­sa­tion for heart fail­ure in pa­tients with type-2 di­a­betes and es­tab­lished car­dio­vas­cu­lar dis­ease or mul­ti­ple CV risk fac­tors.

Farx­i­ga is the first SGLT2 in the Unit­ed States to se­cure ap­proval in this pa­tient pop­u­la­tion, As­traZeneca in­di­cat­ed on Mon­day.

Pa­tients with di­a­betes are of­ten af­flict­ed with oth­er co­mor­bidi­ties, such as obe­si­ty, CV dis­ease, and kid­ney prob­lems. SGLT2 mak­ers have been clam­or­ing for a broad­er mar­ket share by dif­fer­en­ti­at­ing their drugs on the ba­sis of ther­a­peu­tic im­pact on these in­ter­sect­ing in­di­ca­tions — but the ma­jor, most lu­cra­tive bat­tle­ground is the heart.

The ap­proval em­anates from da­ta tab­u­lat­ed in the DE­CLARE-TI­MI 58 study, which tracked the CV im­pact of Farx­i­ga ver­sus a place­bo over a pe­ri­od of up to five years in more than 17,000 adults. In the tri­al, the ther­a­py hit one of two pri­ma­ry ef­fi­ca­cy end­points.

The re­sults showed that the Farx­i­ga treat­ment did trig­ger a low­er rate of hos­pi­tal­iza­tion for heart fail­ure — but the ther­a­py was not bet­ter or worse than place­bo in its im­pact on the rate of ma­jor ad­verse car­dio­vas­cu­lar events (MACE), de­fined as car­dio­vas­cu­lar death, my­ocar­dial in­farc­tion, or is­chemic stroke.

On the pri­ma­ry goal of MACE — 8.8% of Farx­i­ga pa­tients and 9.4% in the place­bo group suf­fered MACE events (haz­ard ra­tio: 0.93; P=0.17), al­though the dif­fer­ence was not deemed sta­tis­ti­cal­ly sig­nif­i­cant. On the oth­er end­point, Farx­i­ga did re­sult in a low­er rate of car­dio­vas­cu­lar death or hos­pi­tal­iza­tion for heart fail­ure (4.9% in the Farx­i­ga arm vs. 5.8% on the place­bo group; P=0.005), which re­flect­ed a low­er rate of hos­pi­tal­iza­tion for heart fail­ure (haz­ard ra­tio, 0.73); there was no be­tween-group dif­fer­ence in car­dio­vas­cu­lar death.

The FDA ap­proval fol­lows a sim­i­lar up­date to the drug’s la­bel by the EMA  in Au­gust.

Farx­i­ga, akin to In­vokana from J&J $JNJ and Jar­diance from Eli Lil­ly $LLY, be­longs 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. Al­though the class of drugs is unit­ed by sim­i­lar­i­ties, In­vokana’s la­bel is crip­pled with the risk of am­pu­ta­tion, un­like Jar­diance and Farx­i­ga.

In Sep­tem­ber, As­traZeneca un­veiled da­ta from the DA­PA-HF tri­al, which showed the drug cut the risk of CV death or the wors­en­ing of heart fail­ure in pa­tients with heart dis­ease.

The 4,744-pa­tient tri­al test­ed Farx­i­ga in pa­tients with re­duced ejec­tion frac­tion (HFrEF) — in which the heart mus­cle is not able to con­tract am­ply and, there­fore, ex­pels less oxy­gen-rich blood in­to the body — on stan­dard of care treat­ment, in­clud­ing those with and with­out type-II di­a­betes.

Farx­i­ga re­duced the com­pos­ite end­point of car­dio­vas­cu­lar (CV) death or wors­en­ing of heart fail­ure by 26% (p<0.0001) — in­clud­ing a re­duc­tion in each of the in­di­vid­ual com­po­nents of the end­point. Da­ta showed there was a 30% de­crease (p<0.0001) in the risk of ex­pe­ri­enc­ing a first episode of wors­en­ing heart fail­ure and an 18% cut (p=0.0294) in the risk of death from car­dio­vas­cu­lar caus­es.

Farx­i­ga, which was ap­proved for use in type-II di­a­betes back in 2014 — whose sales un­der­whelmed an­a­lyst ex­pec­ta­tions in the sec­ond quar­ter — is al­so be­ing eval­u­at­ed for pa­tients with heart fail­ure in the DE­LIV­ER (HF­pEF) and DE­TER­MINE (HFrEF and HF­pEF) tri­als, in ad­di­tion to chron­ic kid­ney dis­ease in the DA­PA-CKD tri­al. Its ri­vals are test­ing their di­a­betes of­fer­ings in a range of heart and kid­ney tri­als as well.

Late last month, the FDA ex­pand­ed In­vokana’s la­bel to slow the pro­gres­sion of di­a­bet­ic nephropa­thy (DKD), as well as to re­duce the risk of hos­pi­tal­iza­tion for heart fail­ure in pa­tients with type II di­a­betes and DKD — an in­di­ca­tion that no oth­er type II di­a­betes med­i­cine is ap­proved for.

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End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

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Douglas Love, Annexon CEO

An­nex­on’s GA drug miss­es on pri­ma­ry goal but win on vi­su­al acu­ity will be fo­cus of planned late-stage tri­al

Annexon’s complement inhibitor didn’t prove better than sham at reducing lesion growth in a leading cause of blindness, but the biotech still plans to move forward on the back of secondary endpoints showing visual acuity preservation, which will “certainly” be the primary goal in a late-stage trial to be discussed shortly with the FDA, CEO Douglas Love told Endpoints News. 

The California biotech’s ANX007 was not statistically significant compared to pooled sham, the comparator, at 12 months in patients with geographic atrophy, per a Wednesday presentation. In every-month dosing, the GA lesion area changed about 6.2% from baseline (p=0.526) and 1.3% (p=0.896) in the every-other-month group. In a March note, Jefferies analyst Suji Jeong said a reduction of 20% to 30% would be “encouraging.”

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FDA ap­proves Lex­i­con’s heart-fail­ure drug af­ter de­feat in di­a­betes

The FDA on Friday approved Lexicon’s heart failure drug sotagliflozin following a string of setbacks for the pharma company, including an FDA rejection in diabetes and the loss of a development deal with Sanofi.

The dual SGLT1 and SGLT2 inhibitor will be marketed as Inpefa and is a once-daily tablet. It’s been approved to reduce the risk of cardiovascular death and heart failure-related hospitalization or urgent visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The label spans the range of left ventricular ejection fraction, including preserved ejection fraction and reduced ejection fraction, as well as patients with or without diabetes, Lexicon said Friday.

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Teresa Bitetti, Takeda's president of the global oncology business unit

Take­da wins pri­or­i­ty re­view for $400M col­orec­tal can­cer drug, li­censed from Hutchmed in Jan­u­ary

Takeda and Hutchmed scored a priority review Thursday afternoon for a colorectal cancer drug, the companies announced.

The experimental drug in question is fruquintinib, previously approved in China in 2018 to treat metastatic colorectal cancer. Takeda and Hutchmed are aiming to bring fruquintinib to the US and other countries outside China in the same indication, and the FDA set its decision date for Nov. 30 of this year.

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Eu­ro­pean Com­mis­sion to re­ceive few­er Pfiz­er-BioN­Tech vac­cine dos­es un­der amend­ed con­tract

The European Commission has made a few changes to its vaccine contract with Pfizer and BioNTech, reducing the dose volume while extending the delivery timeline to cope with “evolving public health needs.”

The Commission previously struck a contract in May 2021 for 900 million doses, with the option to purchase another 900 million. Of those, 450 million were expected to be delivered in 2023, though an amendment now calls for fewer doses. While neither the Commission nor Pfizer and BioNTech have revealed an exact amount, an unnamed source told Reuters that the amendment reduces the remaining expected doses by about a third.

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EMA rec­om­mends re­vok­ing au­tho­riza­tion of No­var­tis' sick­le cell drug

The European Medicines Agency’s committee for medicinal products for human use (CHMP) on Friday recommended revoking the marketing authorization for Novartis’ treatment for a painful complication related to sickle cell, after a recent study did not confirm its clinical benefit.

CHMP’s review looked at results of the STAND study, finding that Adakveo (crizanlizumab) did not reduce the number of painful crises leading to a healthcare visit, and patients treated with Adakveo had slightly more painful crises on average, with a subsequent healthcare visit, over the first year of treatment, compared with those on placebo.

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Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

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Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

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