As­traZeneca's di­a­betes drug Farx­i­ga cuts risk of CV death or wors­en­ing of heart fail­ure by 26% in land­mark study

About two weeks af­ter As­traZeneca’s $AZN un­veiled its di­a­betes treat­ment Farx­i­ga cut the risk of CV death or the wors­en­ing of heart fail­ure in pa­tients with heart dis­ease, in a land­mark tri­al — over the week­end the British drug­mak­er pre­sent­ed de­tailed da­ta at the Eu­ro­pean So­ci­ety of Car­di­ol­o­gy (ESC) Con­gress in Paris.

The re­sults em­anat­ed from the 4,744-pa­tient DA­PA-HF tri­al, which 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.

John Mc­Mur­ray Uni­ver­si­ty of Glas­gow

Farx­i­ga “did all the things we would like any drug to do in heart fail­ure, which are to im­prove symp­toms, re­duce hos­pi­tal ad­mis­sions and in­crease sur­vival. Even bet­ter, Farx­i­ga was as ef­fec­tive in heart fail­ure pa­tients with­out di­a­betes as in those with di­a­betes,” John Mc­Mur­ray of the Uni­ver­si­ty of Glas­gow said in a state­ment on Sun­day.

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

Farx­i­ga, akin to J&J’s $JNJ In­vokana and Eli Lil­ly’s $LLY Jar­diance, be­long 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.

Last year, As­traZeneca pre­sent­ed mixed da­ta on Farx­i­ga from a large study in type-II di­a­betes pa­tients at risk for CV dis­ease or es­tab­lished CV dis­ease. In the DE­CLARE-TI­MI 58 tri­al, which in­clud­ed more than 17,000 pa­tients, Farx­i­ga met one of the main goals by con­fer­ring a sta­tis­ti­cal­ly-sig­nif­i­cant re­duc­tion in the com­pos­ite end­point of hos­pi­tal­iza­tion for heart fail­ure or CV death. But it failed to clear the co-pri­ma­ry end­point of re­duc­ing ma­jor ad­verse car­dio­vas­cu­lar events (MACE) ver­sus place­bo.

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 de­vel­oped 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.

Months ago, In­vokana da­ta in­di­cat­ed the drug con­ferred car­dio­vas­cu­lar (CV) ben­e­fit in pa­tients who do and do not have pre­ex­ist­ing CV dis­ease.

So­cial im­age: As­traZeneca, AP Im­ages

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Vas Narasimhan (AP Images)

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Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Isaac Veinbergs, Libra CEO

With $29M in Se­ries A, Boehringer-backed Li­bra looks to tack­le neu­rode­gen­er­a­tion through cel­lu­lar clean­ing

Can the natural process by which cells clean out toxic proteins be harnessed to create potential treatments for neurodegenerative disorders?

That’s the question Libra Therapeutics will be trying to answer, as the new biotech officially launched Wednesday morning with $29 million in Series A financing. The company has three preclinical programs at the ready, with its lead candidate targeting ALS and frontotemporal dementia. But CEO Isaac Veinbergs said he hopes to develop therapies for a wide range of diseases, including Parkinson’s, Alzheimer’s and Huntington’s.

Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Gene Wang, Immetas co-founder and CEO (file photo)

Im­metas Ther­a­peu­tics nabs $11M Se­ries A to nar­row their bis­pe­cif­ic work tar­get­ing in­flam­ma­tion in age-re­lat­ed dis­eases

How does a biotech celebrate its two-year anniversary? For Immetas Therapeutics, it’s with an $11 million Series A round and a game plan to fight age-related disease.

Co-founders Gene Wang and David Sinclair came together years ago around the idea that inflammation is the ultimate process driving age-related illnesses, including cancer. The duo launched Immetas in 2018 and packed the staff with industry experts. Wang, who says he’s always had an entrepreneurial spirit, has held lead roles at Novartis, GSK, Bristol Myers Squibb and Merck. He’s worked on blockbuster drugs like Humira, Gardasil, Varubi and Zolinza. And now, he’s channeling that spirit as CEO.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.