Surgeons at University of Maryland Medical Center performing the first pig-to-human transplant (University of Maryland School of Medicine)

In his­toric first, sur­geons trans­plant a ge­net­i­cal­ly mod­i­fied pig heart in­to a dy­ing pa­tient

Two and a half months af­ter an NYU team du­bi­ous­ly claimed to have per­formed the first ever pig-to-hu­man or­gan trans­plant, a team at the Uni­ver­si­ty of Mary­land Med­ical Cen­ter ap­pears to have ac­tu­al­ly done it.

The cen­ter an­nounced Mon­day evening that sur­geons there suc­cess­ful­ly trans­plant­ed a ge­net­i­cal­ly mod­i­fied pig heart in­to a 57-year-old pa­tient with ter­mi­nal heart dis­ease. The pa­tient, David Ben­nett, was too sick to qual­i­fy for a hu­man donor and had run out of oth­er op­tions.

“I con­sid­er this a tremen­dous break­through for the field,” Jim Mark­mann, head of trans­plant surgery at MGH and a xeno­trans­plant ex­pert not in­volved in the UMD case, said in an email.

In the decades-long ef­fort to make xeno­trans­plan­ta­tion a re­al­i­ty, the new re­port dif­fered from Oc­to­ber’s in key re­spects. Most glar­ing­ly, the pa­tient at NYU was al­ready brain-dead. Doc­tors su­tured a porcine kid­ney to the out­side of her body and could on­ly track whether the pa­tient im­me­di­ate­ly re­ject­ed the for­eign or­gan. As pre­dict­ed by years of mon­key ex­per­i­ments, she didn’t.

Ben­nett, with the doc­tor who per­formed the surgery, Bart­ley Grif­fith

The new pro­ce­dure may of­fer the first test of whether porcine or­gans, when bred with the right bat­tery of ge­net­ic ed­its, can ac­tu­al­ly serve as a re­place­ment or sup­ple­ment to hu­man or­gan do­na­tion and al­low pa­tients to live func­tion­al lives.

So far, so good, ac­cord­ing to UMD, al­though doc­tors cau­tioned that it’s still ear­ly. Ben­nett is do­ing well three days af­ter the pro­ce­dure, the cen­ter said. The New York Times re­port­ed he was still on a heart-lung by­pass ma­chine, but that is com­mon for any new heart trans­plant re­cip­i­ent.

“It was ei­ther die or do this trans­plant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” Ben­nett said, in a state­ment pro­vid­ed by UMD. “I look for­ward to get­ting out of bed af­ter I re­cov­er.”

The news comes as xeno­trans­plan­ta­tion, af­ter years on the med­ical mar­gin, ap­peared to be inch­ing clos­er to re­al­i­ty, po­ten­tial­ly of­fer­ing an al­ter­na­tive to the hun­dreds of thou­sands of pa­tients in the US and around the world wait­ing for or­gans. Af­ter a high-pro­file at­tempt to trans­plant a ba­boon heart in­to a ba­by with a con­gen­i­tal heart de­fect failed in 1983, re­searchers and sev­er­al com­pa­nies tried to use re­com­bi­nant DNA tech­niques to make pigs with or­gans that hu­mans can ac­cept.

Those ef­forts dis­in­te­grat­ed vir­tu­al­ly overnight af­ter the dis­cov­ery of a retro­virus com­mon to pigs, ter­ri­fy­ing health of­fi­cials then deal­ing with the height of the US’s HIV cri­sis. But in the last decade, as fur­ther re­search low­ered con­cerns that porcine en­doge­nous retro­virus, or PERV as the retro­virus is known, can trans­mit to hu­mans and as new genome-en­gi­neer­ing tools be­came avail­able, the field has re­vived it­self.

Ben­nett’s new heart came from Re­vivi­cor, a sub­sidiary of the $9 bil­lion rare dis­ease biotech Unit­ed Ther­a­peu­tics. It’s the same com­pa­ny that pro­vid­ed the NYU kid­ney, but Ben­nett’s heart came from pigs with far more ge­net­ic ed­its: 10 in to­tal — four pig genes knocked out to pre­vent re­jec­tion, six hu­man genes knocked in to pro­mote tol­er­ance, and one ad­di­tion­al pig gene knocked out to pre­vent ex­ces­sive tis­sue growth.

Sci­en­tists are di­vid­ed on the ex­act num­ber of ed­its need­ed to pre­vent re­jec­tion. Re­vivi­cor has been com­pet­ing with a cou­ple aca­d­e­m­ic labs and eGe­n­e­sis, the ven­ture cap­i­tal fa­vorite, to make xeno­trans­plan­ta­tion a re­al­i­ty. eGe­n­e­sis, found­ed by ge­net­ic en­gi­neer Luhan Yang and backed with over $260 mil­lion from pri­vate in­vestors, makes an even high­er num­ber of ed­its — they’ve nev­er said quite how many — as they try to elim­i­nate PERV en­tire­ly.

To be clear, though, Ben­nett’s surgery is still a re­mark­ably ear­ly step by the stan­dard process of drug de­vel­op­ment. The FDA OK’d the pro­ce­dure un­der com­pas­sion­ate use, an emer­gency mea­sure to make ex­per­i­men­tal ther­a­pies avail­able to pa­tients with no oth­er op­tions.

For xeno­trans­plan­ta­tion to ac­tu­al­ly be­come a med­ical­ly ap­proved prod­uct, one com­pa­ny or aca­d­e­m­ic team will have to show the mod­i­fied porcine or­gans are safe and ef­fec­tive in a clin­i­cal tri­al.

Re­vivi­cor, eGe­n­e­sis and oth­ers are try­ing to com­plete the mon­key stud­ies nec­es­sary to re­ceive clear­ance for such a tri­al. They will like­ly need to show the non-hu­man pri­mates have con­sis­tent sur­vival af­ter trans­plant. Ex­perts sug­gest one could be­gin in 2023.

Alexander Lefterov/Endpoints News

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He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

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Dominic Borie, Kyverna Therapeutics CEO

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Dan O'Day (Getty Images)

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Graphic: Alexander Lefterov for Endpoints News

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Roy Baynes, Merck

FDA bats back Mer­ck’s ‘pipeline in a prod­uct,’ de­mands more ef­fi­ca­cy da­ta

Despite some heavy blowback from analysts, Merck execs maintained an upbeat attitude about the market potential of its chronic cough drug gefapixant. But the confidence may be fading somewhat today as Merck puts out news that the FDA is handing back its application with a CRL.

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Florida Gov. Ron DeSantis (AP Photo/Wilfredo Lee, File)

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