Lonafarnib combos offer hope for hepatitis D care, per gobal trial data
Oral therapy seen in large study to ease disease burden, improve liver health
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Among people with chronic hepatitis D (CHD) infection, combination treatment regimens containing lonafarnib show benefits in easing disease burden and improving liver health.
Specifically, the use of the oral therapy alongside other medications in CHD patients is associated with reductions in hepatitis D virus (HDV) burden and normalizations in liver damage markers.
That’s according to new data from a global Phase 3 clinical trial, called D-LIVR (NCT03719313), presented by developer EIT Pharma at the 2026 European Association for the Study of the Liver (EASL) Congress, held late last month in Spain.
“People living with chronic hepatitis D face a serious and progressive liver disease with limited treatment options,” Leen Kawas, PhD, CEO of EIT Pharma, said in a company press release announcing the results of analyses from its lonafarnib development program.
“These new analyses from D-LIVR deepen our understanding of lonafarnib-based regimens for CHD treatment,” Kawas said.
Lonafarnib is already approved in the U.S. and the European Union, under the brand name Zokinvy, for a rare genetic disorder called progeria. It was originally developed for that indication by Eiger Biopharmaceuticals, which then sold the approved therapy to Sentynl Therapeutics. Eiger was also developing lonafarnib for CHD, but that program was suspended in 2023 due to a lack of funds.
Recognizing the lack of treatment options for CHD, EIT acquired the therapy and restarted clinical development. The company noted that it has been working with the U.S. Food and Drug Administration on a path toward regulatory approval, with plans for a new clinical trial to test the long-term benefit of lonafarnib underway.
“The renewed momentum behind lonafarnib is truly exciting,” said Jeffrey Glenn, MD, PhD, professor at Stanford University and an adviser to EIT Pharma on the lonafarnib program. “As the only oral option in late-stage development for chronic hepatitis D, this program represents a critical opportunity for patients with significant unmet medical needs.”
Lonafarnib tested in D-LIVR trial as CHD combo treatment
Viral hepatitis refers to liver inflammation caused by viral infections. CHD is a severe form caused by HDV, and can only occur in people who are already infected with the hepatitis B virus (HBV). Compared with HBV infection alone, CHD is associated with a higher risk of serious complications such as liver failure.
Relative to more common hepatitis types, people with CHD have fewer treatment options. The disease is often managed with antiviral medications to suppress HBV, along with interferon treatment (e.g., peginterferon alfa-2a) to help the immune system fight off the infection. Last month, the injection therapy Hepcludex (bulevirtide-gmod) became the first treatment approved in the U.S. for CHD.
Lonafarnib is an oral medication that blocks farnesyltransferase, an enzyme that’s critical for HDV replication. When the enzyme is blocked, HDV becomes trapped inside the liver cell it’s in, so it can’t spread any further.
The therapy was originally developed by Merck in the 1990s as a cancer drug and later repurposed by Eiger for treating progeria.
After a series of Phase 2 trials, Eiger launched the Phase 3 D-LIVR study, which enrolled more than 400 people with CHD across 21 countries. All were on stable regimens of HBV antiviral treatment.
The trial lasted for 48 weeks, or nearly a year. Participants received twice-daily lonafarnib (50 mg) plus the antiviral ritonavir — with or without weekly injections of interferon therapy — interferon treatment alone, or a placebo. Ritonavir is sold as Norvir, with generics available.
Top-line results, initially reported by Eiger in 2022, showed that significantly more people given lonafarnib/ritonavir — with (19%) or without (10%) interferon — achieved a combined virologic and biochemical treatment response compared with those on the placebo (2%).
A virologic response refers to a prespecified reduction in HDV genetic material, while a biochemical response refers to a normalization of alanine transaminase (ALT), a liver damage marker.
Rates of individual virologic or biochemical responses were also higher with lonafarnib than with the placebo.
Treatment response maintained after 6 months, new data show
More than 40% of lonafarnib-treated patients who achieved a response maintained it six months after treatment was stopped, according to the recent EIT-sponsored oral presentation. The work was titled “Lonafarnib/ritonavir and peg-interferon alfa drive histological improvement and inflammation resolution in chronic hepatitis D: results of the multicenter phase 3 D-LIVR study.”
Moreover, about 10%-20% of people who hadn’t responded during treatment emerged as responders in the six months afterward, the data showed.
In the poster “Lonafarnib/ritonavir with or without peginterferon achieves rapid, durable responses in chronic hepatitis D: extended analyses from the phase 3 D-LIVR trial,” researchers showed that 58% of the people on lonafarnib/ritonavir with interferon and 41% of those on lonafarnib/ritonavir alone achieved a combined treatment response at some point. That compared with 21% of people on interferon alone and 2% of those given the placebo.
The researchers noted that treatment responses were achieved more rapidly with regimens containing lonafarnib than with interferon alone.
[The trial met its main goal, with the lonafarnib combo] demonstrating significant … benefit versus [the] placebo.
The combination of lonafarnib/ritonavir with interferon was also the most effective at normalizing ALT levels, the data showed. Slightly more than half of the patients given that combo experienced meaningful reductions in liver damage without worsening liver scarring, compared with slightly more than a quarter of those in the placebo group.
The treatment was also generally well tolerated, with the most common adverse events being mild to moderate gastrointestinal reactions that occurred in the first month of treatment. These were usually managed with dose reductions or supportive medication, according to the researchers.
The poster states that the combination treatment achieved the trial’s main goal, or endpoint, “demonstrating significant … benefit versus [the] placebo,” with the data “supporting sustained therapeutic impact.”
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