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.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

The drug, known as ofatumumab or Arzerra, has performed consistently well across late-stage trials in patients with the most common form of MS, including in head-to-head studies against Sanofi’s old blockbuster Aubagio. But, if the drug is approved, Novartis will find itself in a crosstown game of catch-up; since a 2017 approval, Roche’s Ocrevus has become the second best-selling MS drug on the market, nearly eclipsing Biogen’s Tecfidera last quarter with over a $1 billion in sales.

Coro­n­avirus out­break threat­ens short­age of 150 drugs — re­port

American patients who suffer from conditions other than Covid-19 could feel the impact of the coronavirus due to shortage of drugs — as 150 prescription drugs are now reportedly on a list of at-risk therapies. The list spans “antibiotics, generics and some branded drugs without alternatives,” Axios reported citing sources familiar with the list. The FDA declined to comment.

Although factories in China are gradually reopening, restrictions in travel and disruptions at transit hubs are still slowing down production. An Indian company that relies on active pharmaceutical ingredients (API) from China told Bloomberg last week that it’s seeing prices of commonly used drugs jump by 40% to 70%.

Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Drug ap­provals: FDA pub­lish­es dataset of CDER ap­provals since 1985

To provide researchers with more accurate and accessible data about historic drug approvals, the FDA on Friday released a dataset containing information about all new drugs and biologics approved by the Center for Drug Evaluation and Research (CDER) dating back to 1985.

“FDA created the compilation to facilitate data accessibility, transparency, and accuracy when researchers seek information about an approved drug,” the FDA writes, adding that the compilation should accurately reflect “the state of each application at the time of initial regulatory approval.”

Deborah Dunsire

The fourth CGRP mi­graine drug is here. Time for Lund­beck to prove it's worth $2B

They may be late, but Lundbeck is now officially in the game for preventing migraine with CGRP drugs.

The FDA has OK’d eptinezumab, the prize in Lundbeck’s $2 billion acquisition of Alder. Like rival offerings from Amgen/Novartis, Eli Lilly and Teva, the antibody blocks the calcitonin gene-related peptide, which is believed to dilate blood vessels in the brain and cause pain.

It will now be sold as Vyepti. The company has yet to announce a price. Amgen and Novartis had set the wholesale acquisition cost of their pioneering Aimovig at $6,900 for a year’s supply before raising it slightly this year; Lilly and Teva had followed suit with Emgality and Ajovy.

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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