PALO ALTO, Calif., April 21, 2017 /PRNewswire/ -- Eiger
BioPharmaceuticals, Inc., (NASDAQ: EIGR) today announced additional
supportive and encouraging lonafarnib (LNF) data from the LOWR HDV
(LOnafarnib With Ritonavir in Hepatitis Delta Virus) Program
presented at The International Liver Congress™ 2017, in
Amsterdam, Netherlands.
After 24 weeks of treatment, all-oral lonafarnib-based regimens
(LNF 25 mg or 50 mg BID + Ritonavir, or RTV) suppressed HDV-RNA
below the limit of quantitation in 36% of patients, and 60%
achieved ALT normalization. The addition of PEG IFN to LNF 25
mg BID + RTV (triple therapy) suppressed HDV-RNA below the limit of
quantitation in 80% of patients, and 78% achieved ALT
normalization. In patients treated for 48 weeks with triple
therapy of PEG IFN + LNF 25 mg BID + RTV, PCR-negativity was
achieved in 67% of patients at the end of treatment.
"The LOWR HDV program was designed to identify optimal
lonafarnib-based regimens to advance in development for the
treatment of HDV, and we're continuing to successfully progress
towards our goal," said David Cory,
President and CEO of Eiger. "Data presented this week
demonstrate multiple encouraging outcomes with lonafarnib-based
regimens including viral load decline greater than 2 logs, viral
load below the limit of quantitation, PCR-negativity, and ALT
normalization. In addition, the finding that anti-HDV
activity is enhanced with the addition of pegylated interferon
alpha to lonafarnib-based regimens is particularly
encouraging. We plan to advance all-oral lonafarnib-based
regimens as well as triple therapy to include pegylated interferon
lambda as potential treatments for HDV."
Key Results from LOWR Program Presentations:
End of Treatment Results at Week 24 (24 weeks
dosing)
All-Oral LNF 25 mg or 50 mg BID + RTV suppresses HDV-RNA at
end of treatment (Week 24)
- 5 of 14 (36%) HDV-RNA < LOQ
(Limit of Quantitation by qPCR)
- 1 of 14 (9%)
PCR-negative
- 4 of 8 (50%) > 2 log
decline in patients with high baseline viral load (HDV RNA > 5
log)
Addition of PEG IFN to LNF 25 mg BID + RTV results in the
highest response rates (Week 24)
- 4 of 5 (80%) HDV-RNA <
LOQ
- 3 of 5 (60%) PCR-negative
- 3 of 4 (75%) > 2 log
decline in patients with high baseline viral load (HDV RNA > 5
log)
ALT normalization achieved in LNF 25 mg or 50 mg BID + RTV
regimens
- 60% (all-oral)
- 78% (with PEG IFN)
Adverse events (AEs) predominantly mild / moderate GI events
with LNF treatment
Post-Treatment Follow-Up at Week 48 (24 weeks dosing + 24
weeks post-dosing)
Addition of PEG IFN to LNF 25 mg BID + RTV led to low-level
viremia off therapy, with PCR negativity in patients at 24 weeks
post-treatment
- 2 of 2 PCR-negative at 24 weeks
post-treatment
End of Treatment Results at Week 48 (48 weeks
dosing)
Addition of PEG IFN to LNF 25 mg BID + RTV
- 2 of 3 (67%) PCR-negative
Additional dosing regimens were also explored in the LOWR
program, including QD dosing of LNF + RTV and dose titration with
BID dosing of LNF + RTV. Anti-HDV activity was observed in
all regimens (LNF 50 mg QD + RTV up to LNF 100 mg BID + RTV)
through Week 24 on treatment. HDV viral load returned to
baseline in a majority of these patients by Week 24 of
post-treatment, suggesting longer-term treatment of all-oral LNF +
RTV or triple combination of LNF + RTV + PEG IFN may be necessary
to achieve sustained antiviral suppression.
"Hepatitis Delta is the most aggressive form of viral hepatitis,
and due to the absence of an approved therapy, HDV infection
remains a significant unmet medical need and a public health
challenge," said Eduardo Martins,
MD, DPhil, Senior Vice President of Liver and Infectious Diseases
Development at Eiger. "Each of the lonafarnib presentations
given at The International Liver Congress™ 2017 highlight the
activity of lonafarnib-based regimens in the treatment of patients
with HDV infection. We look forward to discussing next steps
with regulatory agencies later this year."
Presentations at The International Liver Congress™ 2017:
- Wedemeyer, H. et al; "A Phase 2 Dose-Escalation Study of
Lonafarnib Plus Ritonavir in Patients With Chronic Hepatitis D:
Final Results from The Lonafarnib With Ritonavir in HDV-4 (LOWR
HDV-4) Study"; Abstract #PS-039, Oral Presentation.
- Yurdaydin, C. et al; "A Phase 2 Dose-Optimization
Study of Lonafarnib with Ritonavir for the Treatment of Chronic
Delta Hepatitis—End of Treatment Results from the LOWR HDV-2
Study"; Abstract #GS-008, Oral Presentation.
- Koh, C. et al; "Phase 2 study exploring once daily
dosing of ritonavir boosted lonafarnib for the treatment of chronic
delta hepatitis – end of study results from the LOWR HDV-3 study";
Abstract #LBP-519, Poster Presentation.
- Yurdaydin, C. et al; "The Prenylation Inhibitor Lonafarnib
(LNF) Can Induce Post-Treatment Viral Clearance in Patients with
Chronic Delta Hepatitis (CDH) Resulting in ALT Normalization and
Regression of Fibrosis"; Abstract #THU-161, Poster
Presentation, Oral ePoster Presentation.
- Yurdaydin, C. et al; "Results from Retreatment with
Lonafarnib of a Subset of HDV-Infected Patients"; 13th
Hepatitis Delta International Network (HDIN) Meeting, Oral
Presentation.
LOWR HDV Studies:
The LOWR HDV program was designed to be a multi-center,
international Phase 2 program, to identify dosing regimens and
durations of lonafarnib (LNF) with ritonavir (RTV) ± pegylated
interferon (PEG IFN) to move forward in development for the
treatment of hepatitis delta infection (HDV).
- LOWR HDV – 2 is a dose-finding study to identify combination
regimens of lonafarnib and ritonavir ± PEG IFN α, with efficacy and
tolerability for longer term dosing to enable HDV RNA
clearance. In this open-label study, 58 HDV-infected patients
have been enrolled to date into 10 groups of different doses of
lonafarnib in combination with ritonavir ± PEG IFN α for dosing
durations of 12 to 48 weeks. Lonafarnib doses range from 25
mg BID to 100 mg BID. LOWR HDV – 2 is closing at Ankara University in Ankara, Turkey.
- LOWR HDV – 3 was a double-blinded, randomized,
placebo-controlled study designed to evaluate the efficacy and
tolerability of once-daily doses of lonafarnib – 50 mg, 75 mg and
100 mg – each combined with ritonavir 100 mg once daily for 12 or
24 weeks. Twenty-one patients with chronic hepatitis delta
were randomized into one of six treatment groups. LOWR HDV –
3 was conducted at the National Institutes of Health (NIH) Clinical
Center in Bethesda, Maryland, and
the study has completed.
- LOWR HDV – 4 was an open-label study to evaluate the efficacy
and tolerability of dose escalation of lonafarnib combined with
ritonavir administered twice daily for dosing durations of 24
weeks. Fifteen patients were initiated at lonafarnib 50 mg
and ritonavir 100 mg twice daily, and dose-escalated up to
lonafarnib 100 mg twice daily as tolerated. LOWR HDV – 4 was
conducted at Hannover Medical School in Hannover, Germany, and the study has
completed.
About Sarasar™ (lonafarnib)
Lonafarnib is a well-characterized, late-stage, orally active
inhibitor of farnesyl transferase, an enzyme involved in
modification of proteins through a process called prenylation.
HDV uses this host cell process inside liver cells to
complete a key step in its life cycle. Lonafarnib inhibits
the prenylation step of HDV replication inside liver cells and
blocks the virus life cycle at the stage of assembly.
Lonafarnib has been dosed in over 120 HDV-infected patients across
international academic centers and is in Phase 2 development for
HDV. Lonafarnib has been granted Orphan Drug Designation by
the U.S. Food and Drug Administration (FDA) and European Medicines
Agency (EMA), and Fast Track Designation by U.S. FDA.
Lonafarnib is not approved for any indication, and is licensed from
Merck Sharp & Dohme Corp. (known as MSD outside of the United States and Canada).
About Hepatitis Delta Virus (HDV)
Hepatitis Delta (or Hepatitis D) is caused by infection with HDV
and is considered to be one of the most severe forms of viral
hepatitis in humans. Hepatitis delta occurs only as a
co-infection in individuals harboring Hepatitis B Virus
(HBV). Hepatitis delta leads to more severe liver disease
than HBV alone and is associated with accelerated liver fibrosis,
liver cancer, and liver failure. Hepatitis delta is a disease with
a significant impact on global health, which may affect up to
approximately 15-20 million people worldwide. The prevalence
of HDV varies among different parts of the world. Globally,
HDV infection is reported to be present in approximately 4.3% to
5.7% of chronic Hepatitis B carriers. The prevalence of HDV
in patients infected with chronic HBV is even higher in certain
regions, including certain parts of Mongolia, China, Russia, Central
Asia, Pakistan,
Turkey, Africa, and South
America, with an HDV prevalence as high as 60% being
reported in HBV-infected patients in Mongolia and Pakistan.
About Eiger
Eiger is a clinical-stage biopharmaceutical company committed to
bringing to market novel products for the treatment of rare
diseases. The company has built a diverse portfolio of
well-characterized product candidates with the potential to address
diseases for which the unmet medical need is high, the biology for
treatment is clear, and for which an effective therapy is urgently
needed.
Note Regarding Forward-Looking Statements
This press release contains forward-looking statements that involve
substantial risks and uncertainties. All statements, other
than statements of historical facts, included in this press release
regarding our strategy, future operations, future financial
position, future revenue, projected expenses, prospects, plans and
objectives, intentions, beliefs and expectations of management are
forward-looking statements. These forward-looking statements
may be accompanied by such words as "anticipate," "believe,"
"could," "estimate," "expect," "forecast," "intend," "may," "plan,"
"potential," "project," "target," "will" and other words and terms
of similar meaning. Examples of such statements include, but
are not limited to, whether or not pegylated interferon lambda-1a
or lonafarnib or ubenimex or exendin 9-39 may be further developed
and approved, and whether promising earlier clinical study results
will be repeated in larger, later clinical studies, statements
relating to the availability of cash for Eiger's future operations,
Eiger's ability to develop its drug candidates for potential
commercialization, the timing of the commencement and number and
completion of Phase 2 trials and whether the products can be
successfully developed or commercialized. Various important
factors could cause actual results or events to differ materially
from the forward-looking statements that Eiger makes, including the
risks described in the "Risk Factors" sections in the Annual Report
on Form 10-K for the period ended December
31, 2016 and Eiger's periodic reports filed with the SEC.
Eiger does not assume any obligation to update any
forward-looking statements, except as required by law.
Investors: Ingrid Choong, PhD,
Eiger BioPharmaceuticals, 650-619-6115, ichoong@eigerbio.com
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