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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Sergio Traversa, Relmada Therapeutics CEO

Rel­ma­da makes 'crit­i­cal changes' to PhI­II tri­al to try and save de­pres­sion drug

Relmada Therapeutics is making changes to its Phase III study of its lead drug for major depressive disorder, in an attempt to avoid problems with a prior trial that showed little difference between the drug and a placebo.

That failure in October wiped 80% from Relmada’s stock price, and was followed by another negative readout a few months later. In both cases, the company said that there had been trial sites that were associated with what it called surprising placebo effects that skewed the results compared with the drug, REL-1017.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Peter Hecht, Cyclerion Therapeutics CEO

Hard pressed for cash, Cy­cle­ri­on looks for help fund­ing rare dis­ease drug

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

Paul Song, NKGen Biotech CEO

NK cell ther­a­py-fo­cused biotech eyes SPAC deal

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

In­cyte hit by CRL on ex­tend­ed-re­lease JAK tablets, mud­dy­ing plans for Jakafi fran­chise ex­pan­sion

The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Alaa Halawa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.