Once again No­var­tis’ car­dio team looks to beat the odds us­ing sketchy da­ta and a fa­mil­iar ar­gu­ment

When­ev­er a clin­i­cal tri­al team starts tout­ing the “to­tal­i­ty” of the da­ta, you know they’re in trou­ble.

Bioreg­num Opin­ion Col­umn by John Car­roll

For No­var­tis’ En­tresto (sacu­bi­tril/val­sar­tan) team, that’s the ear­ly go-to po­si­tion on their lat­est round of piv­otal da­ta for the block­buster — which the phar­ma gi­ant be­lieves has megablock­buster po­ten­tial. We al­ready knew that No­var­tis’ team plans to field the drug to reg­u­la­tors in search of a la­bel ex­ten­sion — but now we have a bet­ter idea of the hur­dles it faces. 

And they are steep.

En­tresto flat failed the pri­ma­ry end­point in re­duc­ing the com­pos­ite pri­ma­ry end­point of to­tal (first and re­cur­rent) heart fail­ure hos­pi­tal­iza­tions and car­dio­vas­cu­lar death — hit­ting a 13% re­duc­tion among heart fail­ure pa­tients with pre­served ejec­tion frac­tion (HF­pEF). The p-val­ue was 0.059, which means they couldn’t prove their case for the drug.

No­var­tis’ po­si­tion that this was a nar­row miss rarely pass­es muster at the FDA.

Then they made a sketchy move, switch­ing to a sub-pop­u­la­tion analy­sis which is sure to at­tract lots of skep­ti­cism among reg­u­la­tors — many of whom would have been in­volved in shut­ting down No­var­tis’ last play on that in car­dio with canakinum­ab, where the team shot (and missed) at a par­tic­u­lar sub-pop­u­la­tion where they felt the drug could suc­ceed com­mer­cial­ly. 

Stick­ing with “in­di­vid­u­als with a left ven­tric­u­lar ejec­tion frac­tion equal to or be­low the me­di­an of 57%” in this new study, re­searchers teased out a 22% re­duc­tion on the end­point. In women, it was 27.5%.

“While the re­duc­tion in the pri­ma­ry end­point was not sta­tis­ti­cal­ly sig­nif­i­cant, the to­tal­i­ty of ev­i­dence from PARAGON-HF sug­gests po­ten­tial over­all ben­e­fit of sacu­bi­tril/val­sar­tan com­pared with val­sar­tan in HF­pEF, par­tic­u­lar­ly in pa­tients with ejec­tion frac­tion be­low nor­mal. It al­so high­lights the com­plex­i­ty of HF­pEF and may sug­gest that some treat­ments have a more pro­nounced im­pact in cer­tain pa­tient groups, in­clud­ing women, who are more like­ly to suf­fer from this con­di­tion than men,” said Har­vard’s Scott Solomon in a pre­pared state­ment.

While No­var­tis has been rack­ing up an im­pres­sive slate of pos­i­tive late-stage stud­ies in a va­ri­ety of fields, it hasn’t per­formed well in car­dio — one of the tough­est R&D sec­tors in the busi­ness, where reg­u­la­tors ex­pect pris­tine da­ta be­fore open­ing up la­bels to large num­bers of pa­tients. And No­var­tis likes to push the en­ve­lope in car­dio — though with­out much suc­cess.

Just 9 months ago they trot­ted out pos­i­tive da­ta un­der­scor­ing En­tresto’s abil­i­ty to beat on key sur­vival and re-hos­pi­tal­iza­tion num­bers in a head-to-head study with the cheap ACE in­hibitor enalapril. But some ex­perts in the field al­so ques­tioned why they used a low dose of the cheap ri­val when sig­nif­i­cant num­bers of pa­tients typ­i­cal­ly are pre­scribed a high­er dose.

No­var­tis, though, ap­pears in­tent on test­ing reg­u­la­tors’ in­creased open­ness to some­thing less than the gold stan­dard, mak­ing this a new case study on just what stan­dards the FDA plans to en­force. And if they do get by reg­u­la­tors, they will still face plen­ty of ques­tions from pay­ers, who had erect­ed some stiff bar­ri­ers to this drug af­ter its first ap­proval in 2015.

Ini­tial­ly a slow-mov­ing prod­uct ham­pered by physi­cians re­luc­tant to adopt a new med and pay­ers who were none too hap­py with the price, En­tresto is now com­fort­ably hit­ting its block­buster stride. But No­var­tis wants to add bil­lions more in an­nu­al sales, and its lat­est tri­al fail­ure won’t make that task any eas­i­er.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

Am­gen chops 172 more staffers in R&D, op­er­a­tions and sales amid neu­ro­science ex­it, rev­enue down­turn

Neuroscience wasn’t the only unit that’s being hit by a reorganization underway at Amgen. As well as axing 149 employees in its Cambridge office, the company has disclosed that 172 others nationwide, including some from its Thousand Oaks, CA headquarters, are being let go.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,100+ biopharma pros reading Endpoints daily — and it's free.

Ahead of strate­gic up­date, new Sanofi CEO mulls op­tions for con­sumer health­care arm — re­ports

Big pharma has made moves to sharpen its focus on developing new medicines, while slow-growing consumer health divisions fall by the wayside. Looks like another large drugmaker is considering a similar move. On Thursday, reports citing sources indicated that Sanofi is reportedly mulling a joint venture, sale, or a public listing of its consumer health arm.

The French group is in discussions for options that could value the division at $30 billion, Bloomberg and Reuters reported, citing sources familiar with the matter.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,100+ biopharma pros reading Endpoints daily — and it's free.

The triple crown in biotech: An all-or-noth­ing bet on an FDA ap­proval of 3 drugs over 16 months starts to­day

Bristol-Myers Squibb’s $74 billion Celgene deal closed as expected Wednesday evening. And now a new clock has begun to tick down for Celgene shareholders who came away from the deal with CVRs — contingent value rights — worth $9 or nothing. Those CVRs start trading today as $BMYRT.

The new deadline they have is the end of March 2021, a little more than 16 months from now, when Bristol-Myers will need to gain approvals on 3 late-stage drugs it’s picking up in the buyout: Ozanimod and liso-cel (JCAR017) are due up at the end of 2020, with bb2121 deadlined at the end of Q1 in 2021.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,100+ biopharma pros reading Endpoints daily — and it's free.

Genap­sys fi­nal­ly un­veils vaunt­ed se­quencer, but can it dent Il­lu­mi­na?

Hesaam Esfandyarpour holds what looks like a mini-cooler up to the computer screen in his California office.

Esfandyarpour is in his late-30s, with crows feet creeping up against a youthful face. He wears a gray polo and the device in his hand — with its hard plastic-looking shell, blue-and-white pattern, and a white plastic paddle resembling a handle jutting out the front — might contain diced strawberries and peanut-butter sandwiches to meet mom and the kids at a SoCal park. Instead, Esfandyarpour tells me it’s going to change medicine and biopharma research.

UP­DAT­ED: Make that 2 ap­proved RNAi drugs at Al­ny­lam af­ter the FDA of­fers a speedy OK on ul­tra-rare dis­ease drug

Seventeen years into the game, Alnylam’s pivot into commercial operations is picking up speed.
The bellwether biotech $ALNY has nabbed their second FDA OK for an RNAi drug, this time for givosiran, the only therapy now approved for acute hepatic porphyria. This second approval came months ahead of the February deadline — even after winning priority review following their ‘breakthrough’ title earlier.
AHP is an extremely rare disease, with some 3,000 patients in Europe and the US, not all diagnosed, and analysts have projected peak revenue of $600 million to $700 million a year. The drug will be sold as Givlaari.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,100+ biopharma pros reading Endpoints daily — and it's free.

David Ricks. Eli Lilly

Eli Lil­ly touts $400M man­u­fac­tur­ing ex­pan­sion, 100 new jobs to much fan­fare in In­di­anapo­lis — even though it's been chop­ping staff

Eli Lilly is pouring in $400 million to beef up manufacturing facilities at its home base of Indianapolis. The investment, which was lauded by the city’s mayor, is expected to create 100 new jobs.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 66,100+ biopharma pros reading Endpoints daily — and it's free.

Brii Bio backs in­fec­tious dis­ease start­up while ink­ing deal for its lead TB drug, dou­bling down on an­tibi­otics

Almost two years after leaving GSK to launch Brii Bio with a whopping $260 million in funding, Zhi Hong is seeing the trans-Pacific infectious disease specialist he set out to build take shape.

“Our pipeline is coming together,” he told Endpoints News, with 12 partnered assets plus some internal programs.

As its latest partner, AN2 Therapeutics, comes into the limelight for the first time with a $12 million seed round, so is Brii’s plans in the antibiotics space. Brii has obtained China rights to AN2’s antibacterial targeting mycobacterium tuberculosis for multi-drug resistant TB, which it says is in the clinical stage.

No­var­tis, Bay­er, Long­wood back ge­nomics start­up to speed search for im­munother­a­py tar­gets

Nearly a century passed between the first proto-immunotherapy attempts in cancer — crude and obscure but nonetheless with some scientific basis — and Jim Allison’s first T cell paper. Thirty-plus years flipped between the discovery of CTLA-4 as an off-switch and the approval of Yervoy. Twenty-two rolled between PD-1’s isolation and Opdiva and Keytruda. 

Longwood co-founder Lea Hachigian is betting she can hasten that. It’s a bet on newly established single-cell genomic analysis tech and the ability to crunch endless troves of data at a rate few others can, and investors including Leaps by Bayer and Novartis Venture Fund just put $39 million behind it. They call it Immunitas.