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.”

Fol­low­ing ev­i­dence that the gut is a key dri­ver of meta­bol­ic con­trol, Ra­jagopalan launched Fractyl Lab­o­ra­to­ries with a $5.5 mil­lion Se­ries A round back in 2011. Al­most ex­act­ly a decade lat­er, the com­pa­ny’s back with a $100 mil­lion Se­ries F round and a shiny new name to con­tin­ue the hunt for ther­a­pies to re­verse meta­bol­ic dis­ease.

Fractyl Health will use the Se­ries F funds to ad­vance its en­do­scop­ic ther­a­py, Re­vi­ta DMR, in late-stage stud­ies across the spec­trum of type 2 di­a­betes. The tech­nol­o­gy re­cent­ly re­ceived break­through de­vice des­ig­na­tion, and is ex­pect­ed to com­plete a reg­is­tra­tional tri­al in in­sulin-treat­ed pa­tients in the US in 2023.

Why the sub­tle name change? “We want to stand re­al­ly firm­ly on the side of im­prov­ing health for pa­tients and for so­ci­ety, rather than man­ag­ing dis­ease,” Ra­jagopalan told End­points News. 

The com­pa­ny has raised about $280 mil­lion so far. But when asked whether he has plans to go pub­lic, Ra­jagopalan re­spond­ed: “We don’t have any news to share on that as of now.”

Re­vi­ta DMR makes use of a bal­loon catheter to in­ject saline in­to the walls of the duo­de­num, the first part of the small in­tes­tine im­me­di­ate­ly be­yond the stom­ach. Duo­de­nal lin­ing thick­ens over time due to mod­ern di­ets high in fat in sug­ar. This “cush­ion of saline” thick­ens the lin­ing, in or­der to sep­a­rate it from deep­er struc­tures. The bal­loon then heats up to about 90 de­grees Cel­sius (194 de­grees Fahren­heit), es­sen­tial­ly strip­ping away that ex­ces­sive lay­er. Then the body heals it­self, re­gen­er­at­ing a new, healthy lin­ing which Fractyl be­lieves could re­store in­sulin sen­si­tiv­i­ty.

“The rea­son we tar­get the duo­de­num is be­cause there’s a lot of ev­i­dence that, in peo­ple with type 2 di­a­betes and obe­si­ty, there’s a dys­func­tion­al duo­de­nal sig­nal that’s trig­ger­ing in­sulin re­sis­tance in the liv­er, and that we be­lieve to be one of the very first events in the meta­bol­ic syn­drome,” Ra­jagopalan ex­plained.

Fractyl be­gan en­rolling in the reg­is­tra­tional tri­al, dubbed RE­VI­TA-T2Di, in the first half of this year. The pri­ma­ry end­point in that study is the per­cent­age of pa­tients who achieve glycemic con­trol (de­fined as HbA1c lev­els less than or equal to 7%) with­out the need for in­sulin af­ter 24 weeks.

In a tri­al con­duct­ed in Eu­rope and Brazil, Re­vi­ta DMR didn’t reach sta­tis­ti­cal sig­nif­i­cance in re­duc­tion of HbA1c lev­els in the com­bined pop­u­la­tions, though Ra­jagopalan said the Brazil group was un­der­pow­ered. In just the Eu­ro­pean pop­u­la­tion, me­di­an HbA1c change from base­line was –6.6mmol/mol (17.5mmol/mol) in the Re­vi­ta group, ver­sus –3.3mmol/mol (10.9mmol/mol) in a sham group, with a p-val­ue of 0.033, ac­cord­ing to da­ta pub­lished in the BMJ. 

While Ra­jagopalan be­lieves the pro­ce­dure can ben­e­fit pa­tients for “a very long time,” he’s still un­sure ex­act­ly how of­ten pa­tients might need to re­peat it.

“We’re look­ing for­ward to do­ing some stud­ies in which we can show the re­peata­bil­i­ty af­ter sev­er­al years,” he said.

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.