Pop­u­lar ke­to di­et set to be test­ed in hu­mans to see if it can amp up ef­fect of weak PI3K drugs

Could a pop­u­lar di­et be put on the menu of treat­ment op­tions for some can­cer pa­tients? A new mouse study sug­gests that the an­swer might be yes — and a mar­quee sci­en­tist in the field is set to test it in hu­mans.

Com­bin­ing a ke­to­genic di­et with PI3K in­hibitors like Zy­delig (Gilead) and Aliqopa (from Bay­er) ap­pears to be an ef­fec­tive way to com­bat the in­ter­fer­ence of an in­sulin re­sponse mech­a­nism trig­gered when the drug in­ter­rupts in­sulin pro­duc­tion and then sets off an al­ter­na­tive spike in in­sulin pro­duc­tion which may well be re­spon­si­ble for ei­ther re­duc­ing or elim­i­nat­ing its ef­fi­ca­cy.

Feed­ing mice a ke­to­genic di­et — with high fat, ad­e­quate pro­tein and ex­treme­ly low carbs — was able to low­er blood glu­cose, over­com­ing the treat­ment loop, ac­cord­ing to the study pub­lished in Na­ture. An SGLT2 drug that blocked ab­sorp­tion of glu­cose in the kid­neys al­so had the same ef­fect.

Sid­dhartha Mukher­jee

Now on­col­o­gist Sid­dhartha Mukher­jee — of The Em­per­or of all Mal­adies fame — is set­ting up a 40-pa­tient study with Bay­er to see how this works in hu­mans.

“If you com­bine them with a di­et which [keeps in­sulin low], all of a sud­den these drugs be­come ef­fec­tive,” Mukher­jee told The Guardian. “The di­et re­al­ly works like a drug.”

A new ap­proach to boost the ef­fi­ca­cy of PI3K could have a pos­i­tive im­pact here. Re­searchers have seen poor or weak sur­vival ad­van­tages with these drugs, which spurred Roche to dump taselis­ib a few weeks ago at the end of Phase III.

Gilead’s pi­o­neer­ing Zy­delig got slapped with a black box warn­ing on side ef­fects, forc­ing an end to its quest to com­plete front­line tri­als. Bay­er’s Aliqopa (co­pan­lis­ib) was ap­proved last fall for fol­lic­u­lar lym­phoma pa­tients on the ba­sis of some promis­ing re­sults, crowd­ing a field that Ve­rastem hopes to join with du­velis­ib, a PI3K dropped by In­fin­i­ty Phar­ma­ceu­ti­cals af­ter Ab­b­Vie walked away af­ter get­ting a glimpse of unim­pres­sive — but still ap­prov­able — re­sults.

The ke­to­genic di­et is sim­ple enough. You slash your carbs to a lim­it of 20 grams a day, forc­ing the body to switch to the fat you’re pump­ing in as an al­ter­na­tive en­er­gy source. It’s a proven method for fast weight loss, with most pros in the di­et are­na warn­ing that few adults can sus­tain it. Can­cer re­searchers have al­so stud­ied ke­to to see if starv­ing tu­mors — such as glioblas­toma — of carbs can shut off a key en­er­gy source.

So here come the caveats.

First, mice aren’t hu­mans. 

The re­searchers here al­so aren’t claim­ing that can­cer pa­tients should drop­kick carbs in re­sponse to what they’ve found. For one thing, there still is pre­cious lit­tle hard ev­i­dence that a ke­to di­et alone could sig­nif­i­cant­ly help can­cer pa­tients. And in some cas­es clin­i­cians sus­pect the ap­proach could be counter pro­duc­tive.

Pro­fes­sor Karen Vous­den, Can­cer Re­search UK’s chief sci­en­tist, had this cau­tion­ary note to add to The Guardian about di­et and can­cer: “There’s a lot of black mag­ic and old wives’ tales. None of it is re­al­ly based on any ev­i­dence.”

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

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.

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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.

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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.

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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:

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As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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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.

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.

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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.