Young an­ti-ag­ing field takes big step with Mayo Clin­ic senolyt­ics show­case

The idea that flush­ing senes­cent cells — those old, fa­tigued cells that cease to di­vide — from the body may rid the body of harm­ful pro­teins has been one of the promi­nent pro­pos­als in the an­ti-ag­ing sphere. Hav­ing gen­er­at­ed a stream of an­i­mal da­ta to sup­port the hy­poth­e­sis, the Mayo Clin­ic now has re­sults from an ear­ly hu­man study sug­gest­ing they have found drugs that can do ex­act­ly that.

Latonya Hick­son

To be sure, the main goal of the Phase I tri­al wasn’t to show the ef­fects of de­creas­ing senes­cent cells in the body; rather, the sci­en­tists were keen to prove that a senolyt­ic reg­i­men they’ve test­ed in mice works the same way in hu­mans.

This is sig­nif­i­cant be­cause de­spite the pub­li­ca­tion of first-in-hu­man da­ta in Jan­u­ary, “so far, there has been no di­rect demon­stra­tion of senes­cent cell clear­ance by senolyt­ic drugs in peer-re­viewed pub­lished hu­man clin­i­cal tri­als,” the au­thors wrote in EBio­Med­i­cine.

For the small tri­al, re­searchers de­ployed dasa­tinib and quercetin; the for­mer is a can­cer drug al­so known as Spry­cel while the lat­ter is a plant de­riv­a­tive. Nine pa­tients with di­a­betes-re­lat­ed chron­ic kid­ney dis­ease were re­cruit­ed and giv­en the treat­ments for three days.

Laris­sa Langhi Pra­ta

While the drugs were out of the sys­tem with­in a few days, the ef­fects ap­peared to per­sist, the team — with LaTonya Hick­son and Laris­sa Langhi Pra­ta as the co-first au­thors — re­port­ed:

Key mark­ers of senes­cent cell bur­den were de­creased in adi­pose tis­sue and skin biop­sied from sub­jects 11 days af­ter com­plet­ing the 3-day course of D + Q, as were key cir­cu­lat­ing SASP fac­tors, com­pared to be­fore ad­min­is­tra­tion of these senolyt­ic drugs.

Such proof about the mech­a­nism of ac­tion bol­sters their pre­vi­ous work sug­gest­ing that a brief course of dasa­tinib plus quercetin im­proved phys­i­cal func­tions for pa­tients with id­io­path­ic pul­monary fi­bro­sis — a tough-to-treat dis­ease.

While small-scale, the tri­al is a sig­nif­i­cant step for­ward for the trans­la­tion of senolyt­ic ther­a­pies, ac­cord­ing to Ronald Ko­han­s­ki, deputy di­rec­tor of the di­vi­sion of ag­ing bi­ol­o­gy at the Na­tion­al In­sti­tute of Ag­ing.

“The demon­stra­tion that senes­cent cell num­bers can be re­duced in two tis­sues in hu­mans is an im­por­tant ad­vance based on the com­pelling ev­i­dence from stud­ies in lab­o­ra­to­ry mice,” he said in a state­ment.

James Kirk­land

Chron­ic kid­ney dis­ease is just one of many age-re­lat­ed ail­ments that the team be­lieves senolyt­ics can de­lay, pre­vent or treat, said se­nior au­thor James Kirk­land (who heads Mayo’s Robert and Ar­lene Ko­god Cen­ter on Ag­ing).

His col­leagues at Mayo have pre­vi­ous­ly flagged Alzheimer’s and Parkin­son’s as dis­eases where purg­ing senes­cent cells can make a big dif­fer­ence.

In case any­one gets over­ly ex­cit­ed, though, the sci­en­tists felt the need to con­clude their pa­per with a note of cau­tion:

The field of senolyt­ics is new. The first clin­i­cal tri­al of senolyt­ic agents was on­ly re­port­ed in Jan­u­ary 2019. The find­ings re­port­ed here are pre­lim­i­nary re­sults from an on­go­ing clin­i­cal tri­al of senolyt­ics for treat­ing dys­func­tion in pa­tients with di­a­bet­ic chron­ic kid­ney dis­ease. Few­er than 150 sub­jects have been treat­ed with these drugs in the con­text of clin­i­cal tri­als that we are aware of so far. In ad­di­tion to side ef­fects re­lat­ed to in­di­vid­ual senolyt­ic drugs known from oth­er con­texts in which those drugs have been used, there could turn out to be se­ri­ous side-ef­fects of senolyt­ics as a class, which are not yet known. We cau­tion against the use of senolyt­ic agents out­side the con­text of clin­i­cal tri­als un­til more is known about their ef­fects and side ef­fects.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.