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: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

David Arthur, Salarius Pharmaceuticals CEO

Salarius Phar­ma­ceu­ti­cals sees with­drawals, 3 of 13 pa­tient re­spon­ders in sar­co­ma tri­al

The Houston-based biotech Salarius Pharmaceuticals is lifting the cover on data from a Phase I/II trial for a drug currently on voluntary hold after a patient death, and the results appear to have underwhelmed investors.

Salarius’ candidate, dubbed seclidemstat, is an oral LSD1 inhibitor that is meant to treat Ewing sarcoma and FET-rearranged sarcomas in patients under 12 years old. The biotech had presented data with 13 patients with “first- and second-relapse Ewing sarcoma” who were treated in combination with topotecan and cyclophosphamide.