News brief­ing: Mar­ius sub­mits NDA for oral hy­pog­o­nadism ther­a­py; Cell­tri­on's bil­lion­aire founder steps down

US reg­u­la­tors will soon be look­ing at a new testos­terone re­place­ment ther­a­py, if Mar­ius Phar­ma­ceu­ti­cals has its way.

The Raleigh, North Car­oli­na-based biotech sub­mit­ted on Tues­day an NDA for Kyza­trex, an oral testos­terone un­de­canoate soft gelatin cap­sule aim­ing to treat both pri­ma­ry and sec­ondary hy­pog­o­nadism in men. Should the FDA ac­cept the ap­pli­ca­tion for pri­or­i­ty re­view, Mar­ius ex­pects a PDU­FA date to fol­low rough­ly six months lat­er.

Mar­ius es­ti­mates a pa­tient pop­u­la­tion of about two mil­lion men in the U.S., many of whom the biotech says have giv­en up on treat­ment or choose not to be treat­ed due to a lack of safe op­tions. But the com­pa­ny is hop­ing its Phase III safe­ty da­ta can sway the FDA to­ward ap­proval.

In a late-stage tri­al, more than 96% of par­tic­i­pants com­plet­ed 90 days of treat­ment and achieved av­er­age testos­terone lev­els in the nor­mal range. Kyza­trex al­so demon­strat­ed an av­er­age SBP in­crease of less than 2 mm Hg as mea­sured by ABPM, the stan­dard FDA blood-pres­sure as­sess­ment.

“Based on avail­able da­ta, Mar­ius has gen­er­at­ed the most com­pelling Phase III re­sults in the testos­terone ther­a­py space,” Mar­ius chair­man Hi­man­shu Shah told End­points News. 

The most com­mon side ef­fect in the study was hy­per­ten­sion, and there were no se­ri­ous ad­verse events re­lat­ed to the treat­ment.

Hy­pog­o­nadism is the most com­mon cause of sec­ondary os­teo­poro­sis in men and is a com­mon co­mor­bid­i­ty in oth­er dis­eases like Type 2 di­a­betes and NASH. Mar­ius ex­pects to file for ap­proval in Eu­rope in the first half of 2022. — Max Gel­man

Cell­tri­on’s bil­lion­aire founder and chair­man de­parts for blood-test­ing start­up

Al­most two decades af­ter start­ing Cell­tri­on, co-founder Seo Jung-jin has re­tired from his chair­man role.

Seo — the sec­ond rich­est man in Ko­rea — told Ko­rea Bio­med­ical Re­view he’s tak­ing one more stab at en­tre­pre­neur­ship be­fore he re­tires, this time fo­cus­ing on blood test­ing.

Hav­ing start­ed out in con­tract man­u­fac­tur­ing, Cell­tri­on was an ear­ly mover in the biosim­i­lars busi­ness and re­cent­ly came up with an an­ti­body for Covid-19 that was au­tho­rized for emer­gency use. — Am­ber Tong

Sanofi ponies up €7 mil­lion mile­stone to In­nate Phar­ma

In­nate Phar­ma is just about ready to cash a new check.

The French biotech an­nounced Tues­day that Sanofi has se­lect­ed a tar­get to ad­vance to IND-en­abling stud­ies, trig­ger­ing a €7 mil­lion pay­ment as part of its near­ly half-bil­lion dol­lar col­lab­o­ra­tion with the phar­ma gi­ant. The tar­get, ini­tial­ly dubbed IPH6101/SAR443579, is an NKp46-based NK cell en­gager de­vel­oped with In­nate’s pro­pri­etary mul­ti­spe­cif­ic an­ti­body for­mat.

As part of the col­lab­o­ra­tion, Sanofi will be re­spon­si­ble for all fu­ture de­vel­op­ment, man­u­fac­tur­ing and com­mer­cial­iza­tion of the pro­gram.

In­nate said that the can­di­date has shown an­ti-tu­mor ac­tiv­i­ty in pre-clin­i­cal pri­mate mod­els, which led to its se­lec­tion. The com­pa­ny’s tech­nol­o­gy si­mul­ta­ne­ous­ly tar­gets two ac­ti­vat­ing re­cep­tors, NKp46 and CD16, on NK cells, as well as a tu­mor anti­gen on can­cer cells.

“We be­lieve IPH6101/SAR443579 is the first NKp46-based NK cell en­gager to start de­vel­op­ment, demon­strat­ing the next wave of sci­en­tif­ic in­no­va­tion at In­nate,” In­nate CSO Er­ic Vivi­er said in a state­ment.

Sanofi and In­nate en­tered in­to their col­lab­o­ra­tion in Jan­u­ary 2016. The pair are work­ing on an ad­di­tion­al on­go­ing re­search pro­gram. — Max Gel­man

Tonix Phar­ma­ceu­ti­cals joins forces with Mass Gen­er­al Hos­pi­tal on kid­ney re­jec­tion

Tonix Phar­ma­ceu­ti­cals has inked a sec­ond col­lab­o­ra­tion with Mass­a­chu­setts Gen­er­al Hos­pi­tal to work on its mon­o­clon­al an­ti­body tar­get­ing CD40-lig­and — this time fo­cus­ing on or­gan re­jec­tion in kid­ney trans­plan­ta­tion.

An­ti-CD40-lig­and has been shown to sup­press re­jec­tion and fa­cil­i­tate “trans­plant tol­er­ance,” ac­cord­ing to Tat­suo Kawai, sur­gi­cal di­rec­tor of the Liv­ing Donor Trans­plan­ta­tion and Dial­y­sis Ac­cess Pro­gram at MGH and pro­fes­sor of surgery at Har­vard Med­ical School. Re­searchers in the pro­gram will look at Tonix’s TNX-1500 in kid­ney trans­plan­ta­tion in “a va­ri­ety of mod­els in­clud­ing non-hu­man pri­mates,” the com­pa­ny said in a state­ment.

“There re­mains a sig­nif­i­cant need for new treat­ments to re­duce the tox­i­c­i­ty of cur­rent treat­ments by more se­lec­tive­ly sup­press­ing im­mune re­spons­es or in­duc­ing spe­cif­ic tol­er­ance to the trans­plant­ed or­gan,” Kawai said.

Last year, the com­pa­ny teamed up with MGH to study the can­di­date in heart trans­plan­ta­tion.

De­spite the promise of an­ti-CD40-lig­and ther­a­py, first gen­er­a­tion can­di­dates were lim­it­ed be­cause they in­ter­act­ed with the FcγRII re­cep­tor, rais­ing con­cerns over an in­creased risk of throm­bo­sis, CEO Seth Le­d­er­man said in a state­ment. Sec­ond gen­er­a­tion can­di­dates made up for some of the prob­lem, but ran in­to oth­er is­sues like de­creased ef­fi­ca­cy.

“TNX-1500 is a third gen­er­a­tion an­ti-CD40- lig­and mAb that has been de­signed by pro­tein en­gi­neer­ing to tar­get CD40-lig­and ther­a­peu­ti­cal­ly, while po­ten­tial­ly de­creas­ing FcγRII bind­ing and the po­ten­tial for throm­bo­sis,” Le­d­er­man said. — Nicole De­Feud­is

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Bomb squad called to As­traZeneca vac­cine plant; Lu­men nabs CARB-X award for low-cost an­tidiar­rheal

A plant located in Wrexham, Wales that is packing the Oxford/AstraZeneca Covid-19 vaccine into vials was surrounded by a bomb squad after officials called police to report a suspicious package.

The alert caused a partial evacuation of the plant, the BBC was among those to report Wednesday. The owner of the plant, British drugmaker Wockhardt UK, said it was cooperating with local authorities and that there were no reports of any injuries.

Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.

The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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