
Late-Stage Trial in Chronic Hepatitis D Discontinued Due to Safety Concerns
Several trial participants experienced concerning hepatobiliary events.
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A late-stage clinical trial in patients with chronic hepatitis delta (CHD) infection is being discontinued, according to study sponsor Eiger BioPharmaceuticals.1 The phase 3 LIMT-2 study (NCT05070364) was assessing the efficacy and safety of peginterferon lambda in approximately 160 participants with well-compensated CHD infection.
Findings from a quarterly safety review revealed that 4 patients experienced hepatobiliary events that resulted in liver decompensation. These observations led the Data Safety Monitoring Board to recommend the discontinuation of the trial.
"The study discontinuation is disappointing, especially for patients with chronic hepatitis delta who have limited treatment options," said David Apelian, MD, PhD, MBA, CEO of Eiger, in a statement.1 "We will work closely with the FDA and our investigators to conduct an orderly termination of the LIMT-2 study in the interest of patient safety."
The phase 3, open-label, parallel-arm trial randomly assigned participants with well-compensated CHD infection to receive peginterferon lambda 180 mcg weekly for 48 weeks with 24 weeks of follow-up (n=105) or no treatment for 12 weeks followed by peginterferon lambda 180 mcg weekly for 48 weeks with 24 weeks of follow-up (n=53). All patients also received concomitant therapy with a second generation anti-hepatitis B virus nucleos(t)ide analogues (NUC) for the duration of the study. The trial ultimately enrolled 158 participants across 48 sites in 12 countries.
Notably, treatment data from the second arm was not intended for the primary analysis; instead, it was being used to provide benchmark data in a parallel reference group for the expected rate of hepatitis D virus
ribonucleic acid (RNA) suppression in participants who received 12 weeks of hepatitis B surface antibody (anti-HBV) NUC therapy alone.
The primary end point was durable virologic response at 72 weeks, with hepatitis D virus RNA below the limite of quantitation at 24 weeks post-treatment.
This latest news is yet another blow to the hepatitis D treatment space, as there is a significant unmet need to address what is the most severe of hepatitis infections.
In October 2022, Gilead received a
Nearly half (48%) of subjects in the 10 mg group and 45% of those in the 2 mg group achieved this combined response by 48 weeks, compared with 2% of those in the control group. Twenty percent of those in the 10-mg group, 12% of those in the 2-mg group, and none of those in the control group achieved undetectable level of hepatitis D RNA by 48 weeks. ALT levels had lowered to the normal range by week 48 in 56% of subjects in the 10 mg group, 51% of subjects in the 2 mg group, and 12% of controls. In patients who achieved a combined response by 48 weeks, ALT levels largely normalized by 24 weeks while hepatitis RNA levels continued to fall through 48 weeks.
Notably, the
References
1. Eiger to Discontinue Phase 3 LIMT-2 Trial of Peginterferon Lambda in Patients with Chronic Hepatitis Delta. News release. September 12, 2023. Accessed September 13, 2023. https://www.prnewswire.com/news-releases/eiger-to-discontinue-phase-3-limt-2-trial-of-peginterferon-lambda-in-patients-with-chronic-hepatitis-delta-301925362.html
2. Gilead Receives Complete Response Letter from U.S. FDA for Bulevirtide for the Treatment of Adults with Hepatitis Delta Virus. News release. October 27, 2022. Accessed September 13, 2023. https://www.gilead.com/news-and-press/company-statements/gilead-receives-complete-response-letter-from-us-fda-for-bulevirtide-for-the-treatment-of-adults-with-hepatitis-delta-virus
3. Wedemeyer H, Aleman S, Brunetto MR, et al. A phase 3, randomized trial of bulevirtide in chronic hepatitis d. N Engl J Med. 2023;389(1):22-32. doi:10.1056/NEJMoa2213429
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