Be­yond cold stor­age: Tech­nol­o­gy de­signed to keep or­gans warm, helps liv­er trans­plant pa­tients in key study

Since the 1960s, cold stor­age emerged as the pre­ferred method for or­gan preser­va­tion for trans­plan­ta­tion, but it didn’t tick all the box­es — lim­i­ta­tions such as the risk of ear­ly graft dys­func­tion still con­tribute to chron­ic com­pli­ca­tions. So an up­grade was in or­der. In­stead of flush­ing and pre­serv­ing the pro­cured or­gan at rough­ly freez­ing tem­per­a­tures, new tech­nol­o­gy ac­tu­al­ly keeps the or­gans warm and toasty for trans­plan­ta­tion in a bid to im­prove or­gan ac­ces­si­bil­i­ty and im­prove trans­plan­ta­tion out­comes.

The tech­nol­o­gy, pi­o­neered by An­dover, Mass­a­chu­setts-based Trans­Medics, ap­proved for use by the FDA for lung preser­va­tion, is un­der reg­u­la­to­ry re­view for the heart — and is be­ing test­ed for the liv­er. On Tues­day, the de­vel­op­er un­veiled late-stage da­ta that showed its prod­uct, called the Or­gan Care Sys­tem (OCS) Sys­tem, low­ered the in­ci­dence of ear­ly al­lo­graft dys­func­tion (EAD) — an ini­tial poor func­tion of the trans­plant­ed liv­er that typ­i­cal­ly por­tends poor al­lo­graft and pa­tient sur­vival.

The 300-pa­tient tri­al, chris­tened PRO­TECT, as­sessed the im­pact of the OCS sys­tem on pre­serv­ing and as­sess­ing donor liv­ers in­tend­ed for trans­plan­ta­tion — 153 pa­tients were trans­plant­ed with the OCS Liv­er and 147 pa­tients were on the con­trol group, which em­ployed cold stor­age meth­ods.

The pri­ma­ry ef­fec­tive­ness end­point was the in­ci­dence of EAD in the first 7 days fol­low­ing trans­plant pro­ce­dures, and that was met: 17.3% for OCS ver­sus 30.5% for con­trol (p=0.009). The main safe­ty goal, the av­er­age num­ber of liv­er graft-re­lat­ed se­ri­ous ad­verse events per pa­tient mea­sured over 30 days fol­low­ing trans­plan­ta­tion, was al­so achieved 0.046 for the OCS group, com­pared to 0.075 in the con­trol arm (p<0.0001).

Sec­ondary ef­fi­ca­cy end­points, in­clud­ing a sig­nif­i­cant­ly low­er in­ci­dence of is­chemic cholan­giopa­thy com­pli­ca­tions at 6 months post-trans­plan­ta­tion, were al­so met.

Mal­colm Mac­Con­mara UT South­west­ern

“To our knowl­edge, these re­sults from the OCS Liv­er PRO­TECT tri­al rep­re­sent the first time a new tech­nol­o­gy or ther­a­py has had a pos­i­tive im­pact on both EAD and is­chemic cholan­giopa­thy in liv­er trans­plan­ta­tion,” said Mal­colm Mac­Con­mara, the tri­al’s co-in­ves­ti­ga­tor and di­rec­tor of the or­gan re­search lab at UT South­west­ern Med­ical Cen­ter. “If ap­proved, this would safe­ly ex­pand the uti­liza­tion of donor liv­ers and sig­nif­i­cant­ly in­crease the num­ber of liv­ers avail­able for life-sav­ing trans­plan­ta­tion.”

For now, the OCS sys­tem is ap­proved for lung preser­va­tion — it is de­signed to re­duce the time dur­ing which the lungs lack blood and oxy­gen sup­port out­side of the body. It in­cludes a portable en­clo­sure with me­chan­i­cal and elec­tri­cal com­po­nents used to warm, ven­ti­late and per­fuse the lungs — as well as a lung preser­va­tion so­lu­tion com­bined with packed red blood cells. The trans­plant team can al­so mon­i­tor and as­sess the donor lungs while they are be­ing per­fused be­fore trans­plan­ta­tion.

Ini­tial­ly it was sanc­tioned for use in on­ly stan­dard-cri­te­ria donor lungs, but last year the FDA ex­pand­ed its use in donor lung pairs ini­tial­ly con­sid­ered un­ac­cept­able for trans­plan­ta­tion based on lim­i­ta­tions of cold stor­age preser­va­tion, for ex­am­ple for pa­tients that are ge­o­graph­i­cal­ly dis­tant.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

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

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Robert Califf (Pablo Martinez Monsivais, AP Images, File)

As buzz on Califf FDA nom heats up, in­dus­try and agency in­sid­ers of­fer a strong nod for the ‘per­fect’ choice

For once in this long, dramatic road to finding a new FDA commissioner, there’s been some continuity. Both CNN and Politico reported this weekend that Rob Califf met with President Biden to discuss the permanent commish role, following earlier news broken by the Washington Post that all signs point to Califf.

Although there may be a few Democrats who continue to grandstand about the dangers of COI (Califf has worked for Verily, sits on the board of Centessa Pharmaceuticals, and has other ties to industry research), with the pandemic ongoing and the need for some kind of continuity at FDA mounting, Califf is likely to meet the same fate as when he first won Senate confirmation in 2016, by a vote of 89-4 — Bernie Sanders and 6 others didn’t vote.

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AstraZeneca CEO Pascal Soriot (Raphael Lafargue/Abaca/Sipa USA)

A com­bo of As­traZeneca's Imfinzi and chemo wins where oth­ers have failed in piv­otal bil­iary tract test

Looking to run with the big dogs in the PD-(L)1 class, AstraZeneca’s Imfinzi has a tall hill to climb to compete in an increasingly bustling market. An aggressive combo strategy for the drug has paid off so far, and now AstraZeneca is adding another notch to its belt.

A combo of Imfinzi (durvalumab) and chemotherapy significantly extended the lives of first-line patients with advanced biliary tract cancer over chemo alone, according to topline results from the Phase III TOPAZ-1 study revealed Monday.

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Sean Ianchulev, Eyenovia CEO and CMO

Re­cent court de­ci­sion push­es FDA to re­ject and re­clas­si­fy drug-de­vice com­bo, crush­ing shares

Back in April, the FDA lost a crucial court case in which its broad discretion of regulating medical products that might satisfy the legal definitions of either “drug” and/or “medical device” was sharply curtailed.

In addition to the appeals court ruling that Genus Medical Technologies’ contrast agent barium sulfate (aka Vanilla SilQ) should not be considered a drug, as the FDA had initially ruled, but as a medical device, the agency also was forced to spell out which drugs would transition to devices as a result of the ruling.

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Joan Butterton, Merck Research Laboratories VP of global clinical development, infectious diseases (Merck)

Mer­ck­'s ex­per­i­men­tal HIV drug is­la­travir hits with a PhI­II com­bo win and FDA fil­ing plans

Back in March, Merck and Gilead agreed to a partnership to challenge GlaxoSmithKline on long-acting HIV meds — by combining one drug from both Merck and Gilead that had shown potential. While Gilead brought its capsid inhibitor lenacapavir, Merck brought islatravir into the deal — a small molecule that the pharma acquired in 2012 from a small Japanese firm.

While that partnership is ongoing, islatravir is coming out of 2 Phase III pivotal trials with back-to-back successes and plans to beat a quick advance to the FDA.

Gil Beyen, Erytech CEO

A transat­lantic biotech flags a painful PhI­II can­cer flop, wav­ing a white flag

More than 4 years after little Erytech inflated some rare passion for its stock with upbeat Phase IIb data for their lead drug in pancreatic cancer, they’ve let the air out of the party balloons.

The transatlantic biotech $ERYP put the word out Monday morning that its drug eryaspase flopped in a Phase III pivotal for second line metastatic pancreatic cancer, slamming its stock, which plunged more than 30%.

Preston Klassen, Metacrine CEO

An­oth­er NASH play­er re­treats from bat­tered field af­ter tox­i­col­o­gy study flags po­ten­tial de­lay

NASH, the notorious liver disease afflicting an increasing number of Americans, has always been the focus at Metacrine ever since serial entrepreneur Rich Heyman unveiled the first round of financing all the way back in 2015.

Not anymore.

The San Diego-based biotech is halting its NASH program and choosing instead to prioritize its effort in pushing the same FXR agonist, MET642, into a Phase II trial for inflammatory bowel disease.