NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

A virus may have dri­ven the death of the first pa­tient to re­ceive a ge­net­i­cal­ly mod­i­fied pig heart

Doc­tors may be clos­ing in on an an­swer for why the first hu­man trans­plant­ed with a ge­net­i­cal­ly mod­i­fied pig heart died last month, around 60 days af­ter the pro­ce­dure. If ac­cu­rate, it may amount to an un­forced er­ror at one of the most sen­si­tive mo­ments in mod­ern med­ical his­to­ry.

At a we­bi­nar last month, Bart­ley Grif­fith, the sur­geon who per­formed the pro­ce­dure, re­vealed that the heart pa­tient, 57-year-old David Ben­nett, was in­fect­ed with a pig virus called porcine cy­tomegalovirus, or pCMV.

MIT Tech­nol­o­gy Re­view first re­port­ed late Wednes­day on the we­bi­nar and the de­bate it set off among trans­plant ex­perts.

Al­though the virus is com­mon in pigs and gen­er­al­ly on­ly trig­gers symp­toms in very young pigs, it has pre­vi­ous­ly been linked to poor out­comes when re­searchers trans­plant­ed pig hearts with the in­fec­tion in­to ba­boons.

Grif­fith em­pha­sized they still aren’t sure that the porcine virus con­tributed to Ben­nett’s death, but he pre­sent­ed ev­i­dence that it set off an ul­ti­mate­ly fa­tal cas­cade. It’s par­tic­u­lar­ly no­table be­cause pigs de­vel­oped for hu­man trans­plants are sup­posed to be kept in com­plete­ly pathogen-free fa­cil­i­ties and test­ed for the pres­ence of such in­fec­tions.

When they first no­ticed low lev­els of the virus in the heart af­ter trans­plant, Grif­fith said, they thought it might be an er­ror.

“We thought maybe that lit­tle bit didn’t mean any­thing, that it was prob­a­bly an er­ror,” he said. “Our donor heart was al­leged­ly free of CMV.”

Jay Fish­man, a trans­plant spe­cial­ist at Mass Gen­er­al, told Tech­nol­o­gy Re­view that it ap­peared the virus drove his death. And Joachim Den­ner of the In­sti­tute of Vi­rol­o­gy at the Free Uni­ver­si­ty of Berlin, who led the ba­boon study show­ing the risk of pCMV in pig-to-hu­man trans­plants, told the out­let the same.

Den­ner added that, al­though CMV is hard to de­tect, it could have been found pri­or to the trans­plant with bet­ter test­ing.  He ar­gued, how­ev­er, that the virus was not sole­ly to blame — Ben­nett was very ill — and the pro­ce­dure was still a suc­cess. Ear­ly at­tempts at an­i­mal-to-hu­man trans­plants last­ed mere hours.

The virus is not con­sid­ered to be trans­mis­si­ble to hu­mans.

Tech­nol­o­gy Re­view said Re­vivi­cor, the biotech that de­vel­oped Ben­nett’s heart, de­clined to com­ment. The com­pa­ny, a sub­sidiary of Unit­ed Ther­a­peu­tics, has re­mained large­ly qui­et even as or­gans from its pigs have been used in a se­ries of head­line-grab­bing pro­ce­dures.

Grif­fith al­so point­ed to oth­er is­sues that could have im­pact­ed Ben­nett’s sur­vival, in­clud­ing mis­steps from the trans­plant team. They gave him an­ti­bod­ies from donor blood twice that were lat­er shown to con­tain an­ti-pig an­ti­bod­ies and may have dam­aged his heart.

The doc­tor’s at­tempts to treat the in­fec­tion with an old AIDS drug failed, but Grif­fith ar­gued that, if pCMV in­deed drove his death, it bodes well for the fu­ture of xeno­trans­plan­ta­tion, as Re­vivi­cor, a Har­vard spin­out called eGe­n­e­sis and oth­er com­pa­nies push to launch the world’s first pig-to-hu­man clin­i­cal tri­als.

If Ben­nett’s im­mune sys­tem had re­ject­ed the heart as for­eign, it would be un­clear to re­searchers how to pro­ceed and whether the pigs might need ad­di­tion­al ge­net­ic mod­i­fi­ca­tions to make them com­pat­i­ble. Virus­es, though, can be de­tect­ed.

“If this was an in­fec­tion, we can like­ly pre­vent it in the fu­ture,” Grif­fith said.

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.

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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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

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Matt Gline, Roivant Sciences CEO (Photo by John Sciulli/Getty Images for GLG)

Pfiz­er and Roivant team up again for an­oth­er 'Van­t', set­ting up an­ti-in­flam­ma­to­ry show­down with Prometheus

Pfizer and Roivant are teaming up to launch a new ‘Vant’ aimed at bringing a mid-stage anti-inflammatory drug to market, the pair announced Thursday.

There’s no name for the startup yet, nor are there any employees. Thus far, the new company and Roivant can be considered “one and the same,” Roivant CEO Matt Gline tells Endpoints News. But Pfizer is so enthusiastic about the target that it elected to keep 25% of equity in the drug rather than take upfront cash from Roivant, Gline said.

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Roche HQ in Basel, Switzerland. (Image credit: Kyle LaHucik/Endpoints News)

As com­peti­tors near FDA goal­post, Roche spells out its re­peat Alzheimer's set­back

Before Roche can turn all eyes on a new version of its more-than-once-failed Alzheimer’s drug gantenerumab, the Big Pharma had to flesh out data on the November topline failure at an annual conference buzzier than in years past thanks to hotly watched rivals in the field: Eisai and Biogen’s lecanemab, and Eli Lilly’s donanemab.

There was less than a 10% difference between Roche’s drug and placebo at slowing cognitive decline across two Phase III trials, which combined enrolled nearly 2,000 Alzheimer’s patients. In its presentation at the conference Wednesday, Roche said it saw less sweeping away of toxic proteins than it had anticipated. For years, researchers and investors have put their resources behind the idea that more amyloid removal would equate to reduced cognitive decline.

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SQZ Biotech slash­es head­count by 60% as founder/CEO hits ex­it — while Syn­log­ic lays off 25%

It’s a tough time for early-stage companies developing highly promising, but largely unproven, new technologies.

Just ask SQZ Biotechnologies and Synlogic. The former is bidding farewell to its founder and CEO and slashing the headcount by 60% as it pivots from its original cell therapy platform to a next-gen approach; the latter — a synthetic biology play founded by MIT’s Jim Collins and Tim Lu — is similarly “optimizing” the company to focus on lead programs. The resulting realignment means 25% of the staffers will be laid off.

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Lynn Baxter, Viiv Healthcare's head of North America

Vi­iV dri­ves new cor­po­rate coali­tion in­clud­ing Uber, Tin­der and Wal­mart, aimed at end­ing HIV

ViiV Healthcare is pulling together an eclectic coalition of consumer businesses in a new White House-endorsed effort to end HIV by the end of the decade.

The new US Business Action to End HIV includes pharma and health companies — Gilead Sciences, CVS Health and Walgreens — but extends to a wide range of consumer companies that includes Tinder, Uber and Walmart.

ViiV is the catalyst for the group, plunking down more than half a million dollars in seed money and taking on ringmaster duties for launch today on World AIDS Day, but co-creator Health Action Alliance will organize joint activities going forward. ViiV and the alliance want and expect more companies to not only join the effort, but also pitch in funding.

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AbCellera founder and CEO Carl Hansen (L) and Rallybio CEO Martin Mackay

Rally­bio, Ab­Cellera form new part­ner­ship around an­ti­bod­ies for rare dis­ease

Two biotechs that have been working heavily on different stages of antibody candidate development over the past several years are looking to work together to find potential candidates for rare diseases.

Canadian-based AbCellera and Connecticut-based Rallybio have entered a strategic partnership to find, develop and commercialize antibodies primarily for rare diseases. The multi-year, multi-target deal will seek to combine AbCellera’s antibody “discovery engine” with Rallybio’s expertise in rare diseases. However, the dollar amount for the deal was not disclosed.