- Lonafarnib/ritonavir response rate of 10.1%
(p=0.0044)
- Lonafarnib/ritonavir in combination
with peginterferon alfa response rate of 19.2%
(p<0.0001)
- Peginterferon alfa comparator arm,
included for contribution of effect, response rate of
9.6%
- Key secondary endpoint of proportion of
patients with improvement in histological response rate
demonstrated with statistical significance in combination arm vs
placebo
PALO
ALTO, Calif., Dec. 8, 2022
/PRNewswire/ -- Eiger BioPharmaceuticals, Inc. (Nasdaq: EIGR), a
commercial-stage biopharmaceutical company focused on the
development of innovative therapies for hepatitis delta virus (HDV)
and other serious diseases, today announced topline primary Week 48
data from its landmark Phase 3 D-LIVR study (N=407)
evaluating lonafarnib, a first-in-class prenylation inhibitor, in
two regimens in patients with chronic HDV: lonafarnib boosted with
ritonavir alone (all-oral) and in combination with peginterferon
alfa (combination). The composite primary endpoint was a ≥2 log
decline in HDV RNA and normalization of alanine aminotransferase
(ALT) at the end of 48 weeks of treatment compared to placebo.
Topline Week 48 results showed that both treatment arms achieved
statistical significance over placebo in the composite primary
endpoint as well as the component virologic and biochemical
responses. Study participants receiving the all-oral therapy and
combination therapy showed a composite response of 10.1% (p=0.0044)
and 19.2% (p <0.0001), respectively, compared to those receiving
placebo (1.9%). Study participants receiving the all-oral therapy
and combination therapy showed statistically significant improved
rates of ALT normalization of 24.7% (p=0.003) and 34.4%
(p<0.0001), respectively, compared to those receiving placebo
(7.7%). A peginterferon alfa comparator arm was included in the
study to show contribution of effect. The composite response rate
in the all-oral arm was comparable to the peginterferon alfa arm
(10.1% vs 9.6%). The composite response rate in the combination arm
was twice that of the peginterferon alfa arm (19.2% vs 9.6%).
The key secondary histological endpoint was defined as ≥2-point
improvement in histological activity index (HAI) and no worsening
of Ishak fibrosis scoring as determined by blinded assessment of
paired liver biopsies (n=229) collected at baseline and Week 48.
This was demonstrated in 35 of 66 patients (53%, p=0.0139) with
statistical significance in the combination arm versus 8 of 30
patients (27%) receiving placebo. Response was demonstrated in 35
of 107 patients (33%, p=0.61) in the all-oral arm versus placebo.
Response in the peginterferon alfa comparator arm was 10 of 26
patients (38%).
Remaining secondary endpoints including virologic, biochemical,
and composite responses at Week 72 (24-weeks post-treatment) are
being collected and are expected to be reported mid-2023.
"We would like to extend our sincere gratitude to the patients,
investigators, and clinical study sites for their participation in
this well-controlled, landmark study," said David Cory, President and CEO, Eiger. "As we
continue to analyze these topline data to fully understand the
efficacy and safety profile of lonafarnib-based treatments in
chronic HDV, we look forward to a pre-NDA meeting with FDA in the
coming quarter and seeing the full dataset including the 24-week
post-treatment data."
"The results of this landmark study highlight three key
findings," said Ohad Etzion, MD,
Director, Department of Gastroenterology and Liver Diseases at
Soroka University Medical Center and D-LIVR study co-lead
investigator. "First, a small subset of patients with chronic HDV
infection may achieve virologic and biochemical improvements with
an all-oral regimen after 48 weeks of treatment. Second, combining
lonafarnib and ritonavir with peginterferon alfa demonstrated the
potential to nearly double the response rate. And third, and
perhaps most importantly, based on these data, combination
treatment may lead to significant histologic improvement, a
generally accepted surrogate for improved future clinical outcomes
for patients. We look forward to the 24-week post-treatment results
of this study for assessment of the potential for finite therapy
for chronic HDV infection."
The majority of treatment emergent adverse events (TEAEs) were
mild or moderate in severity. The most frequent TEAEs associated
with lonafarnib treatment were gastrointestinal. Nine percent and
8% of patients discontinued treatment from the lonafarnib oral and
combination therapy arms, respectively, compared to 2% of patients
in each of the peginterferon alfa and placebo groups. In the
lonafarnib treatment groups, 8% and 14% of patients, respectively,
reported serious treatment-emergent adverse events, compared with
10% in the peginterferon alfa group and 4% in the placebo group.
There were two deaths in the study: one patient treated with
peginterferon alfa died due to decompensated cirrhosis that was
attributed to drug therapy. The other death in the
lonafarnib/ritonavir arm was deemed unrelated to study drug.
Summary of Topline Data
Response Rate, %
(n)
|
Virological/Biochemical Endpoints
|
Placebo
(n=52)
|
LNF +
RTV
(n=178)
|
LNF + RTV +
Alfa
(n=125)
|
Alfa
(n=52)
|
Composite
Endpoint
|
1.9 %(1)
|
10.1% (18)
(p=0.0044)
|
19.2% (24)
(p<0.0001)
|
9.6 %(5)
|
≥2 Log Decline in HDV
RNA
|
3.8 %(2)
|
14.6% (26)
(p=0.0026)
|
32% (40)
(p<0.0001)
|
36.5 %(19)
|
ALT
Normalization
|
7.7 %(4)
|
24.7% (44)
(p=0.003)
|
34.4% (43)
(p<0.001)
|
11.5 %(6)
|
Histological
Endpoint
|
Placebo
(n=30)
|
LNF +
RTV
(n=107)
|
LNF + RTV +
Alfa
(n=66)
|
Alfa
(n=26)
|
≥2-Point Improvement in
HAI
Score and No Worsening in
Ishak Fibrosis Score
|
27 %(8)
|
33% (35)
(p=0.61)
|
53% (35)
(p=0.0139)
|
38 %(10)
|
LNF=lonafarnib;
RTV=ritonavir; Alfa=peginterferon alfa; HAI=histological activity
index
|
Eiger plans to engage with regulatory agencies, beginning with a
pre-NDA meeting with FDA anticipated in Q1 2023, to discuss
pathways for regulatory submissions. The full D-LIVR
dataset, including analyses of the 24-week post-treatment
period, would be included in potential regulatory
submissions. Eiger intends to present D-LIVR study
results at a future medical congress and publish in a peer-reviewed
journal.
ABOUT D-LIVR
D-LIVR (Delta Liver Improvement
and Virologic Response in HDV) is a global,
multi-center, Phase 3 study to evaluate two lonafarnib-based
treatments: an all-oral arm of lonafarnib boosted with ritonavir
(n=178) and a combination arm of lonafarnib boosted with ritonavir
combined with peginterferon alfa (n=125), with each arm compared to
a placebo arm (n=52), in HDV-infected patients after 48 weeks of
treatment. The study also includes a peginterferon alfa
comparator arm (n=52) used to demonstrate contribution of effect
only. The two lonafarnib containing arms are not required to
demonstrate superiority over peginterferon alfa. The study
also includes a 24-week post-treatment follow up period.
The primary endpoint is a composite of a ≥2 log decline in HDV
RNA and ALT normalization at end of 48 weeks of treatment. Key
virological and biochemical secondary endpoints include the
components of the primary endpoint. The key secondary histological
endpoint is defined as ≥2-point improvement in histological
activity index (HAI) and no worsening of fibrosis by Ishak score.
Blinded baseline and Week 48 paired liver biopsies were read by a
single, central reader. Additional secondary endpoints were
included in the post-treatment follow up period. An independent
data safety monitoring board reviews the safety data from
D-LIVR throughout the conduct of the trial, including during
the post-treatment follow-up phase.
With 407 patients enrolled across 116 clinical trial sites in 22
countries, D-LIVR is a landmark study generating the single
largest source of HDV patient data from a well-controlled clinical
trial to better understand and characterize this devastating
disease.
About Hepatitis Delta Virus
(HDV)
HDV is the most severe form of human viral hepatitis, occurring
only as a co-infection in individuals infected with hepatitis B
virus (HBV). HDV leads to more severe liver disease than HBV
alone and is associated with accelerated liver fibrosis, liver
cancer, and liver failure. It is estimated that 60% of HDV infected
patients die within ten years. Approved nucleos(t)ide
treatments for HBV only suppress HBV DNA, do not affect HBsAg and
have no impact on HDV. HDV is a disease with a significant
impact on global health, which may affect up to 15-20 million
people worldwide. Globally, HDV infection is reported to be present
in approximately 4% to 6% of patients with chronic HBV.
About Lonafarnib
Lonafarnib is a well-characterized, first-in-class, oral
prenylation inhibitor which inhibits a host enzyme, blocking a
critical step in HDV viral assembly. Lonafarnib has been dosed in
over 450 chronically infected HDV patients across global clinical
sites, including the Phase 3 D-LIVR
study. Lonafarnib was previously approved by the FDA and in
Europe under the trade name
Zokinvy® for the treatment of progeria (Hutchinson-Gilford progeria
syndrome and progeroid laminopathies). Lonafarnib is not
FDA-approved for the treatment of patients with chronic HDV.
Lonafarnib has been granted Orphan Drug designation by
the U.S. Food and Drug Administration (FDA) and
the European Medicines Agency (EMA), Fast Track
designation and Breakthrough designation by FDA and PRIME
designation by EMA. Eiger licensed exclusive worldwide rights
to lonafarnib from Merck, known as MSD outside of the U.S and
Canada.
About Eiger
Eiger is a commercial-stage biopharmaceutical company
focused on the development of innovative therapies for HDV and
other serious rare diseases. The Eiger HDV platform includes two
first-in-class therapies in Phase 3 that target critical host
processes involved in viral replication. All
five Eiger rare disease programs have been granted FDA
Breakthrough Therapy designation.
For additional information about Eiger and its
clinical programs, please visit www.eigerbio.com.
Forward-Looking
Statements
This press release contains forward-looking statements within
the meaning of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. All statements other than statements
of historical facts, including statements regarding our future
financial condition, timing for and outcomes of clinical results,
prospective products, preclinical and clinical pipelines,
regulatory objectives, business strategy and plans and objectives
for future operations, are forward-looking statements.
Forward-looking statements are our current statements regarding our
intentions, beliefs, projections, outlook, analyses or current
expectations concerning, among other things, the timing of our
ongoing and planned clinical development; the timing of additional
analyses from our Phase 3 D-LIVR study, including virologic,
biochemical, and composite responses at Week 72 (24-weeks
post-treatment) and histologic improvement; the potential benefits
of lonafarnib-based treatments for patients with hepatitis delta
virus (HDV), including the potential response rate of lonafarnib
boosted with ritonavir in combination with peginterferon alfa; the
ability to submit an application for, and obtain marketing approval
from, FDA or any other regulatory body for lonafarnib-based
treatments for the treatment of HDV; and the potential for success
of any of our products or product candidates. Various important
factors could cause actual results or events to differ materially
from the forward-looking statements that Eiger makes, including
additional applicable risks and uncertainties described in the
"Risk Factors" sections in the Quarterly Report on Form 10-Q for
the quarter ended September 30, 2022
and Eiger's subsequent filings with the SEC. The forward-looking
statements contained in this press release are based on information
currently available to Eiger and speak only as of the date on which
they are made. Eiger does not undertake and specifically disclaims
any obligation to update any forward-looking statements, whether as
a result of any new information, future events, changed
circumstances or otherwise.
Contacts
Investors:
Sylvia Wheeler
Wheelhouse Life Science Advisors
swheeler@wheelhouselsa.com
Media:
Sarah Mathieson
SVP, Corporate Affairs
smathieson@eigerbio.com
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