FDA (Image: AP)

FDA to Lex­i­con: Yeah, that's still gonna be a no from us

Lex­i­con’s last hopes for a quick res­ur­rec­tion of its Type 1 di­a­betes drug in the US have been quashed.

The Texas-based biotech an­nounced that the FDA’s Of­fice of New Drugs has de­clined its ap­peal of the com­plete re­sponse let­ter from the agency re­ject­ing their SGLT1/2 drug. The sec­ond re­jec­tion is the lat­est bump in a long, rough slide for a com­pa­ny whose drug so­tagliflozin once gar­nered $300 mil­lion up­front and $1.4 bil­lion in po­ten­tial mile­stones to be Sanofi’s new prospec­tive di­a­betes block­buster.

Lex­i­con ex­ecs im­me­di­ate­ly switched fo­cus to an ap­peal it now plans to make to CDER, but shares $LXRX con­tin­ued their long-run­ning fall, drop­ping 14% to $3.03 on Mon­day. Shares went for over $13 as re­cent­ly as June of 2018.

Lex­i­con and Sanofi showed up late to the game, af­ter J&J, As­traZeneca, and Eli Lil­ly and Boehringer In­gel­heim had col­lec­tive­ly rolled out 3 SGLT in­hibitors. But those drugs were ap­proved for on­ly Type 2 di­a­betes and tar­get­ed ei­ther SGLT 1 or SGLT 2. Lex­i­con promised to hit both of the glu­cose-reg­u­lat­ing pro­teins and get the drug ap­proved for Type 1 di­a­betes.  Be­gin­ning in Sep­tem­ber 2016, they an­nounced suc­cess­ful tri­al re­sult af­ter suc­cess­ful tri­al re­sult.

Lex­i­con CEO Lon­nel Coats

But when it came time for reg­u­la­to­ry re­view, the FDA’s out­side ex­perts hes­i­tat­ed. A coun­cil of 16 split down the mid­dle, 8-8, on whether to ap­prove the drug. The prob­lem was so­tagliflozin ap­peared to raise the risk of di­a­bet­ic ke­toaci­do­sis (DKA), a po­ten­tial­ly life-threat­en­ing con­di­tion that aris­es when the body runs out of in­sulin and starts to break down fat too quick­ly. Break­ing down the fat, the liv­er cre­ates ke­tones that turn the blood acidic.

“While all pa­tients with type 1 di­a­betes may to some de­gree be at risk for DKA, so­tagliflozin ther­a­py clear­ly in­creas­es that risk, and the risk may be un­pre­dictable,” reg­u­la­to­ry staff wrote.

The re­view­ers large­ly agreed that even if the drug was ap­proved, the DKA risk would make it on­ly ac­cept­able for a se­lect group of par­tic­u­lar­ly at­ten­tive T1 pa­tients. Shares tum­bled 25%

The FDA re­ject­ed the drug in March. Shares tum­bled an­oth­er 24%.

Mul­ti­ple Phase III fail­ures in Type 2 di­a­betes fol­lowed. Sanofi had seen enough. They ex­it­ed the deal, and shares tum­bled 70%.

In Sep­tem­ber, the phar­ma gi­ant paid $260 mil­lion to of­fi­cial­ly close the door on the part­ner­ship deal. Lex­i­con’s stock ac­tu­al­ly perked up: 21%.

This isn’t it, though, ei­ther for Lex­i­con or the drug so­tagliflozin. The EMA ap­proved the drug for Type 1 di­a­betes pa­tients and de­spite mixed-at-best re­sults from Phase III tri­als, the com­pa­ny is plow­ing ahead in Type 2. They said in their Q3 call they’re aim­ing for reg­u­la­to­ry sub­mis­sions on both con­ti­nents in the first half of 2020.

As for Sanofi? It’s not just di­a­betes; every busi­ness is un­der re­view. 

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,900+ biopharma pros reading Endpoints daily — and it's free.

Iterum's fu­ture looks un­cer­tain, af­ter lead an­tibi­ot­ic fails con­sec­u­tive piv­otal stud­ies

While the market for antibiotics remains in tatters — unlike many of its bankrupt (or at the brink of bankruptcy) peers — Iterum is suffering not because its antibiotic isn’t selling, but because the compound has now failed back-to-back late-stage studies.

The experimental drug, sulopenem, was designed to tackle drug-resistant infections with an outpatient focus (in addition to hospitals), to avert those reimbursement challenges that incentivize hospitals to prescribe cheaper, generic broad-spectrum antibiotics.

Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,900+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: Did in­sid­ers cash in on pos­i­tive news re­port about Gilead be­fore pub­li­ca­tion?

A series of bullish trades on Gilead options just before the release of a favorable news story is raising questions among regulatory experts, Reuters reported.

On April 16, just hours before STAT published anecdotes from a Chicago hospital that served as one of the clinical sites to test Gilead’s remdesivir in Covid-19 patients, the California-based company’s shares were trading at around $75. Four large blocks of options were purchased for about $1.5 million each, betting that the stock would rise beyond that to as much as $87.5 by mid-August.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,900+ biopharma pros reading Endpoints daily — and it's free.

Roche nabs front­line OK for Avastin/Tecen­triq in com­mon liv­er can­cer, best­ing an old Bay­er drug

For the first time in 12 years, the FDA has approved a new frontline treatment for the most common form of liver cancer.

The agency okayed a combination of Roche’s anti-VEGF antibody Avastin and their immunotherapy Tecentriq for patients with unresectable or metastatic hepatocellular carcinoma (HCC). The approval comes two weeks after Roche and their big biotech sub Genentech published Phase III results showing the combo improved both progression-free survival and, crucially, helped patients live longer than the long-running standard-of-care, Bayer’s Nexavar.

Jean-Jacques Bienaimé, BioMarin chairman and CEO

Bio­Marin holds the line on bleeds with 4-year val­rox up­date on he­mo­phil­ia A — but what's this about an­oth­er de­cline in Fac­tor 8 lev­els?

BioMarin has posted some top-line results for their 4-year followup on the most advanced gene therapy for hemophilia A — extending its streak on keeping a handful of patients free of bleeds and off Factor VIII therapy, but likely stirring fresh worries over a continued drop in Factor VIII levels.

We just don’t know how big a drop.

We’ll see more data when the results are presented at the World Federation of Hemophilia in a couple of weeks. But in a statement out Sunday night, BioMarin $BMRN reported that none of the patients required Factor VIII treatment, adding:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 81,900+ biopharma pros reading Endpoints daily — and it's free.

IPOs abound in the time of coro­n­avirus, as For­ma Ther­a­peu­tics pen­cils in $150M Nas­daq de­but

The IPO engine is thriving, never mind the rampage of the coronavirus crisis on R&D timelines.

On Friday, along with synthetic lethality-focused biotech Repare Therapeutics, another Bristol Myers partner Forma Therapeutics also unveiled its plans to vault on to the Nasdaq — penciling in a target of $150 million.

The Watertown, Massachusetts-based company — which poached senior Genentech executive Frank Lee to take over the reins last year after more than a decade under founder Steve Tregay — raised a plump $100 million late last year, while shepherding its sickle cell disease (SCD) drug through an early-stage trial.