LBP13
A Phase 2 Study of Peginterferon Lambda, Lonafarnib and
Ritonavir for 24 Weeks: End-of-Treatment Results from the LIFT
HDV Study
Christopher Koh1, Julian Hercun1, Farial Rahman1, Amy Huang1,
Ben Da1, Pallavi Surana1, Devika Kapuria1, Yaron Rotman1,
Anusha Vittal1, Christy Ann Gilman1, Gil Ben Yakov1, Walter Lai1,
Harel Dahari2, Jeffrey Glenn3, Theo Heller1. 1NIDDK/NIH, Bethesda,
United States; 2Loyola University, Chicago, United States; 3Stanford
University School of Medicine, Stanford, United States
Email: [email protected].
Background and aims: Hepatitis Delta Virus (HDV) infection, the
most aggressive form of human chronic viral hepatitis, is still without
an approved FDA therapy. Clinical trials have demonstrated anti-HDV
activity with the prenylation inhibitor lonafarnib (LNF) boosted with
ritonavir (RTV) and peginterferon lambda-1a (LMD) monotherapy. In
a first-in-humans clinical trial, the Lambda InterFeron combination
Therapy (LIFT) study evaluated the safety and antiviral effects of
combination therapy with LMD/LNF/RTV in patients with chronic
HDV infection.
Method: In this phase 2a open-label study, 26 adult patients with
chronic HDV and quantifiable HDV RNA in serum (lower limit of
quantitation <40 IU/mL) have completed treatment with subcutaneous
LMD 180 mcg weekly and oral LNF 50 mg and RTV 100 mg twice
daily for 24 weeks and are undergoing per-protocol post-therapy
monitoring for 24 weeks. Tenofovir or Entecavir was started prior to
therapy. Serial assessments of safety parameters, liver tests, pharmacokinetics,
histology, and virologic (HDV RNA and HBV DNA) markers
were obtained.
Results: In this ongoing study, patients were 62% male, median age of
40 years and included Asian (54%), White (31%) and African (15%)
subjects. Median baseline evaluations included: ALT (62 IU/mL), AST
(47 IU/mL), Ishak Fibrosis (3), modified HAI inflammation (9), HBV
DNA (<21 IU/mL) and log HDV RNA (4.7 IU/mL). After 12 weeks of
therapy, the median HDV RNA decline from baseline was 3.4 log IU/mL (IQR: 2.9–3.8, p < 0.0001) with 7 patients (27%) achieving
undetectable HDV RNA and 6 patients (23%) with HDV RNA below
the lower limit of quantification (BLOQ). At the end of therapy, the
median HDV RNA declinewas 3.4 log IU/mL (IQR: 2.9–4.5, p < 0.0001)
with 11 patients (42%) achieving undetectable HDV RNA and 3
patients (11%) BLOQ. 25 of 26 patients (96%) achieved >2 log decline
during 24 weeks of therapy. Adverse events were mostly mild to
moderate and included GI related side effects, weight loss, hyperbilirubinemia,
and anemia. Therapywas dose reduced in 3 patients and
discontinued in 4 patients.
Conclusion: Triple combination therapy with LMD/LNF/RTV in
chronic HDV patients appears to be safe and tolerable for up to 6
months in most patients. After 24 weeks, almost all achieve >2 log
decline in HDV RNA during therapy with >50% achieving undetectable
or BLOQHDV RNA levels. These end-of-treatment results support
continued exploration of this therapeutic combination in HDV.作者: StephenW 时间: 2020-8-25 22:17