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.”

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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How Chi­na turned the ta­bles on bio­phar­ma's glob­al deal­mak­ing

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

An­gion's or­gan dam­age drug strikes out again, this time in high-risk kid­ney trans­plant pa­tients

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

An image of Alzheimer's brain tissue. The red show gingipains, a protein from P. gingivalis, intermixing with neurons (yellow) and glial cells (green)

An Alzheimer's dark­horse fails its first big tri­al, but of­fers hope for a long-over­looked hy­poth­e­sis

Three years ago, Cortexyme emerged out of obscurity with some big-name backers and an unorthodox approach to treating Alzheimer’s.

They moved their drug into a pivotal study the next year, offering one of the first major tests for a hypothesis that has fluttered on the outskirts of Alzheimer’s research for decades: that, in many cases, the disease is driven by infectious agents — the havoc they wreak in the brain and the inflammation the body uses to try to fend them off. And that quashing the infection could slow patients’ cognitive decline.

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No­var­tis dumps AveX­is pro­gram for Rett syn­drome af­ter fail­ing re­peat round of pre­clin­i­cal test­ing

Say goodbye to AVXS-201.

The Rett syndrome gene therapy drug made by AveXis — the biotech that was bought, kept separate, then renamed and finally absorbed by Novartis into its R&D division — has been dropped by the biopharma.

In Novartis’ third quarter financial report, the pharma had found that preclinical data did not support development of the gene therapy into IND-enabling trials and beyond. The announcement comes a year after Novartis told the Rett Society how excited it was by the drug — and its potential benefits and uses.

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Peter Nell, Mammoth Biosciences CBO

UP­DAT­ED: Jen­nifer Doud­na spin­out inks a Mam­moth CRISPR deal with Ver­tex worth near­ly $700M

When a company gets its start in gene editing pioneer Jennifer Doudna’s lab, it’s bound to make headlines. But three years in, the fanfare still hasn’t died down for Mammoth Biosciences. Now, the Brisbane, CA-based company is cheering on its first major R&D pact.

Mammoth unveiled a nearly $700 million deal with Vertex on Tuesday morning, good for the development of in vivo gene therapies for two mystery diseases. The stars of the show are Mammoth’s ultra-small CRISPR systems, including two Cas enzymes licensed from Doudna’s lab over the past couple years, Cas14 and Casɸ.

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FDA is much worse than its reg­u­la­to­ry peers at proac­tive­ly dis­clos­ing da­ta, re­searchers find

The European Medicines Agency and Health Canada continue to outpace the FDA when it comes to proactively releasing data on drugs and biologics the agency has reviewed, leading to further questions of why the American agency can’t be more transparent.

In a study published recently in the Journal of Law, Medicine, & Ethics, Yale and other academic lawyers and researchers found that between 2016 and April 2021, the EMA proactively released data for 123 unique medical products, while Health Canada proactively released data for 73 unique medical products between 2019 and April 2021. What’s more, the EMA and Health Canada didn’t proactively release the same data on the same drugs. In stark contrast, the FDA in 2018 only proactively disclosed data supporting one drug that was approved that year.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.