Higher Donor BMI Tied to Improved Lung Transplant Survival

Lung transplant patients who received a lung from obese donors had a 15-20% reduction in mortality at 1 year in one of the first studies to examine the impact of donor body mass index (BMI) and post-transplant survival.

Findings from the retrospective trial, which included data on patients and donors registered with the United Network for Organ Sharing Standard Transplant and Analysis database, suggest that donor obesity may confer a protective benefit for transplanted lungs.

The findings were presented this week in a poster session at the virtual CHEST conference, the annual meeting of the American College of Chest Physicians.

The BMI of lung transplant recipients has been shown to be an independent predictor of mortality, with studies showing an increased risk of death following transplant in patients who are either underweight or overweight, said Sung Choi, MD, of Rutgers New Jersey Medical School in Newark, who presented the findings.

For example, in a 2017 study involving over 17,000 lung transplants performed in the U.S. from 2005 to 2016, underweight and overweight lung recipients (i.e., BMI ≤20 and ≥28 at the time of listing) were found to be at increased risk for both short- and long-term mortality.

Recipient weight-loss prior to lung transplantation was also associated with a reduction in mortality and days on mechanical ventilation in a 2015 study, with greater reductions in BMI associated with greater survival benefit.

And, in a 2014 consensus statement, the International Society for Heart and Lung Transplantation recommended that a BMI of 30 or greater be considered a relative contraindication to lung transplantation.

Regarding donor BMI, however, Choi told MedPage Today that there hasn’t been prior research examining the impact on lung recipient outcomes and that the findings from his team’s study were a surprise: “We really weren’t expecting this result,” he said.

“We thought greater donor BMI might be associated with an increase in recipient mortality or maybe a null finding. What we found was striking to us. There appeared to be a dose-dependent relationship, with higher donor BMI associated with lower recipient mortality at 90 days and 1 year after the transplant,” Choi said.

Close to 16,000 adult patients who received single- or double-lung transplants from 2005 to 2018 were included in the analysis. Median age of the lung recipients was 59, and roughly 60% were male. Donors were categorized as underweight (BMI <18.5), normal weight (18.5 to <25), overweight (25 to <30), class I obesity (30 to <35), class II obesity (35 to <40), and class III obesity (≥40.0).

Average donor BMI was 25.9, and 45% were classified as normal weight.

A survival benefit at 1 year was observed among patients who received a lung transplant from donors in obesity class 1 (HR 0.867, 95% CI 0.772-0.975, P<0.01) and obesity classes II/III (HR 0.804, 95% CI 0.688-0.941, P<0.01) compared with lungs from normal-weight donors, the researchers reported.

In adjusted analyses, the team reported lower odds of survival with increased donor age, male sex, and presence of diabetes.

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Terns Pharmaceuticals to Present Clinical Data on Improved TERN-101 Tablet Formulation at the Paris NASH Digital Experience

Terns Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company focused on developing best-in-class single-agent and combination therapies to treat non-alcoholic steatohepatitis (NASH) and other liver diseases, announced today the presentation of new clinical data on an improved tablet formulation of its liver-distributed farnesoid X receptor (FXR) agonist TERN-101 at the Paris NASH Digital Experience, taking place virtually October 22-23, 2020. The presentation, entitled “Comparative pharmacokinetics of two oral formulations of nonsteroidal farnesoid X receptor agonist TERN-101 in healthy volunteers,” demonstrated that an amorphous tablet formulation of TERN-101, which is currently being evaluated in the Phase 2a LIFT study in NASH patients, achieved faster absorption and higher plasma levels compared to a previous crystalline capsule formulation of TERN-101. The study results also demonstrate that the new formulation reduces pharmacokinetic variability and that TERN-101 can be administered without regard to food.

“In Terns’ Phase 1 studies, TERN-101 has demonstrated potent FXR activation in the liver and is well tolerated, with no observation of pruritus and no difference from placebo in serum lipid effects. We’ve now developed an improved formulation that optimizes absorption and minimizes PK variability,” said Erin Quirk, M.D., President and Chief Medical Officer of Terns. “This new TERN-101 formulation is now being studied in our 12-week Phase 2a LIFT study in NASH patients, and we look forward to seeing the results in mid-2021.”

Full details from the presentation can be found at www.ternspharma.com/scientific-publications.

About TERN-101 and Farnesoid X Receptor (FXR) Agonism

TERN-101 is a potent, non-steroidal FXR agonist, with enhanced liver distribution being developed for the treatment of NASH. FXR is a nuclear receptor that is highly expressed in the liver and small intestine. FXR agonism has demonstrated improvement over placebo in regression of histological liver fibrosis without progression of NASH in a late-stage study, demonstrating the potential for FXR agonists to be a new treatment modality for NASH. TERN-101 has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of NASH.

About NASH

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), which is caused by the accumulation of excess fat in the liver. NASH is associated with chronic liver inflammation and liver cell injury, and it can lead to fibrosis, cirrhosis, and eventually liver cancer or liver failure. Global rates of NAFLD and NASH are increasing rapidly, in tandem with rising rates of obesity. There is currently no approved medication for the treatment of NASH.

About Terns Pharmaceuticals

Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing best-in-class single-agent and combination therapies to treat non-alcoholic steatohepatitis (NASH) and other liver diseases. The company’s liver-selective FXR-agonist, TERN-101, is currently conducting a multi-center, randomized, double-blind, placebo-controlled Phase 2a clinical trial designed to evaluate efficacy, safety, and pharmacokinetics in 96 presumed NASH patients who receive placebo or TERN-101 at various dose levels for 12 weeks. Terns recently announced positive Phase 1 clinical data for its highly selective SSAO inhibitor, TERN-201, demonstrating potent and sustained target engagement. In addition,

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