Keenova Therapeutics plc, the Dublin-headquartered specialty pharmaceutical company formerly known as Mallinckrodt, announced on October 12, 2026, a new exploratory analysis of TERLIVAZ (terlipressin) examining efficacy and safety in adults with hepatorenal syndrome-acute kidney injury (HRS-AKI) who are ineligible for liver transplantation. The analysis, presented at the American College of Gastroenterology Annual Scientific Meeting in Phoenix, Arizona, revisits the pivotal Phase III CONFIRM trial to investigate treatment outcomes in patients who cannot receive a liver transplant. The development addresses a difficult clinical population because terlipressin can improve kidney function, but its established risks include serious or fatal respiratory failure.
The conference presentation comes as separately available exploratory findings from the same CONFIRM dataset provide additional numerical context. An abstract scheduled for presentation at the American Society of Nephrology’s Kidney Week meeting on October 24 reports verified reversal of hepatorenal syndrome in 28.2% of transplant-ineligible patients receiving terlipressin, compared with 16.2% receiving placebo. That analysis also reports a lower incidence of kidney replacement therapy among surviving patients receiving terlipressin, although the observational nature of the subgroup comparison limits causal interpretation.
The distinction between improved kidney function and improved survival remains central to interpreting the findings. TERLIVAZ became the first FDA-approved medicine specifically indicated to improve kidney function in adults with HRS-AKI in September 2022, following years of clinical development. However, its pivotal trial did not demonstrate a survival advantage, and the treatment carries a boxed warning for serious or fatal respiratory failure, making patient selection especially important.
What does Keenova’s new TERLIVAZ analysis reveal about patients ineligible for liver transplantation?
The American College of Gastroenterology presentation is titled Efficacy and Safety of Terlipressin in Patients With Hepatorenal Syndrome-Acute Kidney Injury Ineligible for Liver Transplant: An Exploratory Analysis of the CONFIRM Trial. Nancy Reau, associate director of solid organ transplantation and section chief of hepatology at Rush University Medical Center, is the presenting author. The research team also includes specialists in hepatology, nephrology and clinical research who have investigated the management of advanced liver disease.
Keenova described the analysis as extending understanding of terlipressin use among patients who cannot undergo liver transplantation. This is an important distinction because HRS-AKI develops in patients with advanced liver disease, where kidney dysfunction is often linked to severe disturbances in blood circulation rather than a primary structural kidney disorder. Even when kidney function improves, the underlying liver disease may continue to progress.
The company’s October 12 announcement did not provide detailed numerical results, statistical comparisons or adverse-event rates from the ACG analysis itself. However, the separately published American Society of Nephrology abstract examines a closely related transplant-ineligible CONFIRM population and provides figures that help contextualise the clinical question. These findings should be understood as exploratory subgroup evidence rather than a new prospective trial or an expansion of TERLIVAZ’s approved indication.
The subgroup focus is clinically relevant because liver transplantation can be the definitive treatment for selected patients with advanced cirrhosis and associated hepatorenal syndrome. Patients who are not transplant candidates face a different long-term outlook, and short-term recovery of kidney function may not address the broader consequences of advanced liver disease. Assessing the usefulness of terlipressin in this setting therefore requires attention to kidney recovery, dialysis requirements, treatment complications and survival.
How significant are the 28.2% versus 16.2% kidney reversal findings from CONFIRM?
The publicly available nephrology conference abstract reports that 108 of the 300 patients enrolled in CONFIRM were classified as ineligible for liver transplantation. Of these, 71 had been assigned to terlipressin and 37 to placebo. Verified reversal of hepatorenal syndrome occurred in 28.2% of the terlipressin group and 16.2% of the placebo group, representing an absolute difference of 12 percentage points.
The direction of the treatment difference is consistent with the overall pivotal trial, where the FDA-labelled analysis reported verified HRS reversal in 29.1% of terlipressin-treated patients compared with 15.8% receiving placebo. The findings suggest that the kidney-function response observed in the original study was not confined to patients eligible for transplantation. However, the smaller subgroup limits the precision of conclusions about the magnitude of benefit.
The abstract also describes a narrower subgroup of 73 transplant-ineligible patients after excluding those with specified high-risk clinical characteristics involving severe kidney dysfunction or advanced acute-on-chronic liver failure. Within this population, verified HRS reversal occurred in 35.6% of patients receiving terlipressin compared with 17.9% receiving placebo. This larger numerical treatment difference is potentially relevant to understanding how baseline illness severity influences outcomes.
Nevertheless, the 73-patient comparison involved only 45 terlipressin recipients and 28 placebo recipients. Excluding patients with more severe disease can produce a population with a different likelihood of responding to treatment, and the abstract does not establish a new confirmatory efficacy endpoint for this selected group. The results should therefore be viewed as supportive evidence for risk-based treatment evaluation rather than proof that a particular subgroup will reliably achieve kidney recovery.
Why does the original Phase III CONFIRM trial remain central to TERLIVAZ treatment decisions?
The Phase III CONFIRM trial was a randomised, double-blind, placebo-controlled investigation involving 300 adults with cirrhosis and type 1 hepatorenal syndrome. Participants were assigned in a 2:1 ratio to terlipressin or placebo for up to 14 days, with concomitant albumin administration strongly recommended in both groups. The study was designed to determine whether terlipressin could improve kidney function in a population with rapidly progressive renal impairment.
The primary endpoint was verified reversal of hepatorenal syndrome, requiring two consecutive serum creatinine measurements at or below 1.5 mg/dL, obtained at least two hours apart. Patients also had to remain alive without kidney replacement therapy for at least ten days after achieving the response. This definition was more demanding than observing a single improvement in a laboratory value because it included a short period of sustained clinical stability.
The original 2021 New England Journal of Medicine publication reported verified reversal in approximately 32% of terlipressin recipients versus 17% of placebo recipients, using the trial’s prespecified statistical approach. The FDA prescribing information presents corresponding observed rates of 29.1% and 15.8%, reflecting a different analysis and reporting method. Both presentations support a treatment effect on kidney-function reversal, although the percentages should not be treated as interchangeable calculations.
The pivotal study also showed that the improvement in renal outcomes did not establish a reduction in 90-day mortality. Death occurred in 51% of patients assigned to terlipressin and 45% receiving placebo during that period, a numerical difference that did not demonstrate a survival advantage. This limits the conclusions that can be drawn from the new exploratory analysis because short-term kidney recovery cannot be presented as evidence that terlipressin extends survival in transplant-ineligible patients.
Could TERLIVAZ reduce the need for dialysis in patients with advanced liver disease?
Kidney replacement therapy is a particularly important outcome in HRS-AKI because patients may require dialysis when kidney function deteriorates sufficiently to cause serious metabolic or fluid-management complications. Dialysis can provide temporary support, but treatment decisions become especially complex in patients who cannot undergo liver transplantation. Severe underlying liver disease, haemodynamic instability and other complications can influence both the feasibility and expected benefit of kidney replacement therapy.
The separate nephrology abstract reports that the incidence of kidney replacement therapy was lower among surviving terlipressin recipients than placebo recipients at assessments beginning on day 14 and extending through day 90. This finding provides additional context beyond serum creatinine measurements because it examines whether patients subsequently required a major supportive intervention. However, the abstract does not disclose all the numerical event rates in its text.
The investigators also caution that kidney replacement therapy reflects individual treatment decisions, particularly in patients who are not eligible for transplantation. Clinicians may choose different approaches depending on prognosis, patient preferences, available treatment options and the expected reversibility of the underlying condition. As a result, lower dialysis use cannot automatically be interpreted as proof that terlipressin prevented kidney failure in every patient who avoided treatment.
The analysis additionally considers patients who remained alive during the relevant assessment periods. This introduces an important interpretive issue because death can prevent a patient from subsequently receiving dialysis, and competing outcomes can influence the apparent frequency of kidney replacement therapy. A complete assessment would therefore require detailed information about survival, treatment exposure and competing events rather than examining dialysis incidence in isolation.
The findings nevertheless strengthen the rationale for investigating how kidney recovery affects resource-intensive supportive care. More complete publication of the subgroup analysis would help determine whether the observed differences remain consistent after accounting for baseline characteristics and survival-related factors. Until then, the evidence supports an association between terlipressin treatment and lower reported kidney replacement therapy use within the exploratory population, not a definitive reduction in dialysis requirements across all transplant-ineligible patients.
Why do respiratory failure warnings remain the most important limitation of TERLIVAZ?
TERLIVAZ carries an FDA boxed warning because treatment can cause serious or fatal respiratory failure. The risk is especially relevant in patients with fluid overload or Grade 3 acute-on-chronic liver failure, who may already have compromised respiratory function and substantial systemic illness. These complications represent a major consideration when evaluating a treatment intended to improve kidney function in critically ill patients.
In the primary clinical trial, serious or fatal respiratory failure occurred in 14% of terlipressin-treated patients compared with 5% receiving placebo, according to the FDA prescribing information. The original CONFIRM publication also reported deaths due to respiratory disorders within 90 days in 11% of terlipressin recipients versus 2% of placebo recipients. These findings contributed to the regulatory safety requirements accompanying the drug’s United States approval.
Current prescribing information requires evaluation of oxygenation before treatment and continuous pulse oximetry during administration. TERLIVAZ is contraindicated in patients experiencing hypoxia or worsening respiratory symptoms, and treatment must be discontinued if oxygen saturation falls below specified thresholds. The label also advises avoiding use in patients with Grade 3 acute-on-chronic liver failure because of their increased respiratory risk.
The medication can also cause ischemic complications involving cardiac, cerebrovascular, peripheral and mesenteric circulation. Its vasoconstrictor activity is central to the intended improvement in kidney perfusion, but the same pharmacological mechanism can affect blood flow in other organs. These risks make the relationship between kidney benefit and systemic safety particularly important.
The transplant-ineligible exploratory analysis does not remove these established concerns. Although the nephrology abstract reported no unique safety signals compared with the overall CONFIRM population, that observation does not mean adverse events were absent or that the subgroup was free of serious respiratory complications. Small subgroup sizes also limit the ability to detect differences in uncommon but clinically consequential adverse events.
How does TERLIVAZ work, and why does the severity of kidney dysfunction influence treatment benefit?
Hepatorenal syndrome develops when advanced liver disease produces major disturbances in the circulation, including dilation of blood vessels supplying the abdominal organs and reduced effective arterial blood volume. These changes can activate compensatory systems that constrict blood vessels supplying the kidneys, contributing to reduced renal blood flow and declining filtration. The condition can progress rapidly and is associated with high mortality.
Terlipressin is a vasopressin receptor agonist that increases vascular resistance, particularly within the splanchnic circulation. By reducing excessive splanchnic vasodilation, the medicine can improve effective arterial circulation and help restore kidney perfusion. Its mechanism differs from conventional therapies directed at structural kidney injury because the central problem involves circulatory dysfunction associated with advanced liver disease.
The FDA-approved indication is to improve kidney function in adults with hepatorenal syndrome involving a rapid reduction in kidney function. The prescribing information specifically notes that patients with serum creatinine above 5 mg/dL are unlikely to experience benefit. This limitation is relevant to the exploratory subgroup findings because baseline kidney dysfunction may affect the likelihood of treatment response.
The combination of efficacy and safety considerations helps explain why clinicians must evaluate more than the diagnosis alone. Baseline oxygenation, fluid status, severity of liver failure, renal function and other cardiovascular risks can substantially influence the expected balance of benefit and harm. The new analysis contributes evidence about treatment response in transplant-ineligible patients but does not establish a separate dosing regimen or remove existing label restrictions.
What do the new findings mean for Keenova Therapeutics’ hospital medicines business?
TERLIVAZ is part of Keenova Therapeutics’ branded specialty pharmaceutical portfolio, which includes treatments used in nephrology, critical care and other areas of significant unmet medical need. The company adopted its current name following the November 2025 separation of Par Health after the earlier combination of Mallinckrodt and Endo. Its commercial strategy now focuses on branded medicines, supported by United States manufacturing and distribution operations.
The new conference analysis could support clinical understanding of TERLIVAZ in a population facing particularly difficult treatment decisions. However, it does not represent a new FDA approval, a broader indication or a completed regulatory submission. The immediate commercial implications are therefore more closely connected to medical education and evidence development than to a confirmed expansion of the addressable patient population.
Keenova reported second-quarter 2026 net sales from continuing operations of $517 million and adjusted EBITDA from continuing operations of $206 million. Its larger disclosed product franchises include Acthar Gel and XIAFLEX, while TERLIVAZ sales were not separately identified in the company’s second-quarter product revenue breakdown. This limits the ability to quantify the current contribution of TERLIVAZ or forecast the effect of the exploratory research on company earnings.
The company remains outside national stock exchange trading as of the latest publicly disclosed information. In August 2026, Keenova said it planned to pursue a New York Stock Exchange listing in 2027, subject to corporate approvals and market conditions. Consequently, the October TERLIVAZ announcement cannot be linked to a conventional publicly traded Keenova share-price reaction.
The commercial opportunity in HRS-AKI also requires careful interpretation of disease prevalence. Keenova cited United States research indicating that annual inpatient diagnoses of hepatorenal syndrome increased from approximately 42,930 in 2018 to 63,381 in 2023. These figures describe hospitalisations associated with diagnosed disease rather than the number of patients eligible for TERLIVAZ, which depends on clinical severity, contraindications and other treatment-selection considerations.
What additional evidence could clarify TERLIVAZ’s role in transplant-ineligible HRS-AKI patients?
The next important evidence step will be fuller reporting of the transplant-ineligible subgroup analysis, including baseline clinical characteristics, adverse-event rates and detailed kidney replacement therapy outcomes. Statistical estimates and information about competing risks would make it easier to assess whether the observed treatment differences are robust. Because the population was selected retrospectively from CONFIRM, the analysis should remain hypothesis-generating rather than being treated as another independently positive Phase III trial.
The distinction between kidney-function improvement and overall patient outcomes will remain particularly important. Successful reversal of hepatorenal syndrome can be clinically meaningful, but patients with advanced liver disease remain vulnerable to infection, bleeding, respiratory complications and progressive hepatic failure. Improvements in renal laboratory measurements therefore need to be considered alongside survival, hospital outcomes and the potential burden of treatment.
The publicly available nephrology abstract scheduled for October 24 provides additional evidence on kidney replacement therapy in transplant-ineligible patients, while the October 12 American College of Gastroenterology presentation addresses efficacy and safety in this population. Both analyses draw on the original CONFIRM dataset rather than describing newly recruited clinical trial participants. More complete peer-reviewed reporting would allow clinicians to examine the methods and results in greater detail.
Keenova’s latest research reinforces a clinically important question: whether the established kidney-function benefit of terlipressin remains relevant when liver transplantation is not an available option. The exploratory findings provide supportive evidence of renal response, including a 28.2% verified reversal rate among transplant-ineligible terlipressin recipients versus 16.2% with placebo in the separately reported subgroup analysis. The central consideration remains whether that improvement offers meaningful benefit for individual patients without exposing them to disproportionate respiratory and ischemic risks, particularly given the absence of a demonstrated survival advantage in the pivotal trial.
