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.