Albireo Pharma, Inc. (Nasdaq: ALBO), a clinical-stage rare liver
disease company developing novel bile acid modulators, today
announced new data in progressive familial intrahepatic cholestasis
(PFIC) confirming statistically significant reductions in serum
bile acids (sBAs) and improvements in pruritus for odevixibat, a
potent, once-daily, non-systemic ileal bile acid transport
inhibitor (IBATi). Interim results from the extension study also
showed continued treatment effect for sBAs, pruritus, growth and
liver parameters across PFIC1, PFIC2 and PFIC3 patients. Data to be
presented at the American Association for the Study of Liver
Diseases (AASLD) Liver Meeting November 13-16.
Full results from PEDFIC 1, the first and largest, global, phase
3 study ever conducted in PFIC, confirm both U.S. and EU primary
endpoints were met in the randomized, double-blind,
placebo-controlled trial. Additionally, long-term data from PEDFIC
2, an open-label Phase 3 extension study, demonstrate continued and
durable reductions in sBAs, improvements in pruritus assessments
and encouraging markers of liver and growth function in patients
treated up to 48 weeks. Across both studies, odevixibat was
generally well tolerated, and treatment-emergent adverse events
(TEAEs) were mostly mild or moderate. Collectively, these studies
reaffirm odevixibat’s potential to be the first drug treatment
approved for patients living with PFIC, a devastating disease which
is currently treated with surgical options including liver
transplantation. The data support near-term regulatory filings in
the U.S. and EU.
“The full results from the PEDFIC 1 Phase 3 trial confirm the
magnitude of treatment effects seen in the topline data and
reinforce the potential for odevixibat to alter the biology of PFIC
disease. There were highly statistically significant reductions in
both pruritus and serum bile acids in the PEDFIC 1 study,” said
Richard Thompson, M.D., Ph.D., Professor of Molecular Hepatology at
King’s College London and principal investigator of PEDFIC 1 and
PEDFIC 2. “We saw durability and sustained effect in the interim
results in PEDFIC 2, which are encouraging signs that IBAT
inhibition with odevixibat may offer a transformative treatment and
genuine alternative to surgery for patients with PFIC.”
Final Results
from PEDFIC 1, First
and Largest
Study
Ever in PFIC1 and PFIC2Full
results from PEDFIC 1, the global Phase 3 clinical trial evaluating
the efficacy and safety of odevixibat in children with PFIC,
confirms both U.S. and EU primary endpoints were met in the
placebo-controlled trial. Key findings include:
- Significant reductions in
pruritus and SBAs:
Overall, treatment with odevixibat at both doses of 40 and 120
µg/kg/day led to statistically significant reductions in pruritus
symptoms and serum bile acids over 24 weeks, compared with placebo.
Statistically significant improvement was seen in the proportion of
positive pruritus assessments (p=0.004), which is the U.S.
regulatory primary endpoint. The EU regulatory primary endpoint was
also achieved, which was a 70% reduction in serum bile acids (sBAs)
or reaching a level of 70 μmol/L (p=0.003).
- Rapid, sustained effect:
Rapid onset of treatment effects, sustained through week 24.
- Well tolerated: Odevixibat
was well tolerated, with an overall adverse event incidence not
dose dependent and similar to placebo. There were no drug-related
serious adverse events (SAEs) reported during the study.
Diarrhea/frequent bowel movements were the most common
treatment-related gastrointestinal adverse events, which occurred
in 9.5% of odevixibat treated patients vs. 5.0% of placebo
patients. Only one patient in the 120 µg/kg/day group discontinued
treatment due to an AE of diarrhea.
|
Placebo |
Odevixibat |
P-value |
n=20 |
n=42 |
|
Proportion of positive pruritus assessments
(Mean) |
28.7% |
53.5% |
0.004 |
Clinically meaningful improvement in pruritus
score |
10.5% |
42.9% |
0.018 |
Protocol defined bile acid reduction |
0% |
33.3% |
0.003 |
Absolute change in serum bile acid |
13.1 |
-114.3 |
0.002 |
Drug-related diarrhea/frequent bowel
movements |
5.0% |
9.5% |
---- |
Interim
Results
from PEDFIC 2
Extension
Study
Reaffirm
Odevixibat
Effect in
Treated and
New
Patients The PEDFIC 2 interim
data include results through 24 weeks of treatment (data cutoff
date: July 15, 2020) from 69 patients who received 120 µg/kg/day
oral dose, which is the planned commercial formulation of
odevixibat.
Cohort 1 consists of PFIC1 and PFIC2 patients from PEDFIC 1 who
rolled into PEDFIC 2. This includes patients treated with
odevixibat (patient group P1O), as well as patients treated with
placebo (patient group P1P).
Cohort 2 consists of newly enrolled patients who did not
participate in the PEDFIC 1 trial, including patients with PFIC 1,
PFIC 2, PFIC3 and MYO5B deficiency.
Key findings include:
- Affirmation of efficacy: Mean reductions in
sBAs and improvements in pruritus assessments, height and weight
with odevixibat exposure were observed in all PEDFIC 2 patient
groups.
- Sustained effect: Patients with 48 weeks of
cumulative odevixibat exposure (P10 group) achieved a mean
reduction in sBAs from 251.8 µmol/L to 85.1 µmol//L (p<0.0001)
and a mean monthly improvement in the pruritus score, defined as a
drop from baseline of 1.0 point or more on the 0-4 point scale,
from 3.0 to 1.4 (p<0.0001). Cohort 2 confirms the 24-week data
from PEDFIC 1, reinforcing the decline in sBA and pruritus seen in
the PEDFIC 1 study.
- Encouraging change in height & weight
observed: In patients exposed to odevixibat for 48
weeks (P10), mean height Z scores also improved from –1.6 to –0.5
(p=0.02) from baseline to PEDFIC 2 week 24, and mean weight Z
scores normalized over 48 weeks (–0.9 to 0.2; p=0.03).
- Patients remain on treatment: 93% of treated
patients are on ongoing treatment with odevixibat.
- Improvement across PFIC types 1, 2 and 3:
Subgroup analyses showed rapid effect and improvements in patients
across multiple PFIC subtypes. For example, patients with PFIC 1,
PFIC 2 and PFIC 3 in P1P and cohort 2 had mean reductions vs.
baseline in sBAs of -31.7 umol/L, -120.8umol/L and 126.8 umol/L,
respectively, through week 12.
- Well
tolerated: Odevixibat was
generally well tolerated in PEDFIC 2. Most TEAEs were mild or
moderate. No drug-related serious TEAEs occurred. The incidence of
diarrhea was low (10.1% overall), and no patient experienced severe
diarrhea. No clinically significant changes or safety signals were
noted in laboratory assessments.
“PEDFIC 1 & 2 demonstrated how odevixibat has profound and
durable improvements in multiple parameters, including serum bile
acids, pruritus, height, growth, sleep and liver parameters. Even
more important is we saw a sustained treatment effect across a wide
range of PFIC patients,” said Ron Cooper, President and Chief
Executive Officer of Albireo. “These results give us confidence in
the potential for IBAT inhibition in our pivotal studies in biliary
atresia and Alagille syndrome.”
The PEDFIC 1 (#LO4) and PEDFIC 2 (#LP19) results will be shared
in late-breaking presentations at the American Association for the
Study of Liver Diseases (AASLD) The Liver Meeting Digital
Experience™ (TLMdX®).
Novel Bile Acid Modulator ApproachesAlbireo
will present the latest preclinical data on multiple new approaches
to modulating bile acids in adult liver diseases (#P348) by
targeting certain bile acid transporters: the apical
sodium-dependent bile acid transporter (ASBT) and the
sodium-taurocholate co-transporting peptide (NTCP). This has the
potential to significantly change the bile acid transporter
approach in adult liver diseases by diverting bile acids (BAs) from
the liver through several pathways.
Data from the first preclinical study will be presented on
Albireo’s ASBT inhibitor A3907 (#P509) as a novel intervention for
adult liver diseases. A3907 is a selective ASBT inhibitor being
developed for adult liver diseases, including primary biliary
cholangitis (PBC) and primary sclerosing cholangitis (PSC). Due to
oral bioavailability, A3907 can inhibit ASBT in the intestine and
kidney, with the potential to increase elimination of bile acids by
both fecal and urinary excretion. By using dual pathway diversion
of sBAs, next generation modulators like A3907 seek to improve
efficacy while reducing side effects such as diarrhea, which can be
common with bile acid transport inhibitors today.
Results from the preclinical studies of A3907:
- Demonstrated ability to increase urinary excretion of bile
acids in mice
- Reduced the NAFLD activity score by ≥2 points in >50% and
>40 % of animals at 30 and 45 mg/kg, respectively (p<0.001
and p<0.05 vs. pretreatment)
- Prevented fibrosis stage progression in >50% of animals at
10, 30 and 45 mg/kg (p<0.001, p<0.001, and p<0.01 vs.
pretreatment) in a diet-induced mouse model of biopsy confirmed
NASH
- Significantly reduced plasma levels of transaminases, total
cholesterol, and markers for cell damage and fibrosis, as well as
liver weight and liver total cholesterol levels
“In addition to the exciting results of our work with odevixibat
in PFIC, we are progressing multiple approaches for modulating bile
acids with new compounds like A3907, with the goal of finding new
ways to maximize the approach to increase efficacy without
sacrificing tolerability for patients,” added Cooper. “Our current
work in adult liver diseases represent important pipeline
developments for Albireo and reinforce our scientific leadership in
bile acid modulation.”
Conference CallAlbireo will host a post-AASLD
conference call and live audio webcast on November 17, at 10
a.m. EST. To access the live conference call by phone, please dial
877-407-0792 (domestic) or 201-689-8263 (international) and provide
the access code 13709929. The live audio webcast will be accessible
from the Albireo Media & Investors page:
http://ir.albireopharma.com/. To ensure a timely connection to the
webcast, it is recommended that participants register at least 15
minutes prior to the scheduled start time. An archived version of
the webcast will be available for replay in the Events &
Presentations section of the Media & Investors page of
Albireo’s website for two weeks following the event.
About OdevixibatOdevixibat is an
investigational product candidate being developed to treat rare
pediatric cholestatic liver diseases, including progressive
familial intrahepatic cholestasis (PFIC), biliary atresia and
Alagille syndrome. A highly potent, once-daily, non-systemic ileal
bile acid transport inhibitor (IBATi), odevixibat acts locally in
the small intestine. Odevixibat does not require refrigeration
and can be taken as a capsule for older children, or opened and
sprinkled onto food, which are factors of key importance for
adherence in a pediatric patient population. Odevixibat is
currently being evaluated in the ongoing PEDFIC 2 open-label trial
(NCT03659916) and the BOLD Phase 3 trial in patients with biliary
atresia (NCT04336722). Initiation of a pivotal Phase 3 trial of
odevixibat for Alagille syndrome is also anticipated by the end of
2020.
Odevixibat has received Fast Track, Rare Pediatric Disease and
Orphan Drug Designations in the United States. In
addition, the FDA has granted Orphan Drug Designation to
odevixibat for the treatment of Alagille syndrome, biliary atresia
and primary biliary cholangitis. The EMA has granted
odevixibat Orphan Designation, as well as access to the PRIority
MEdicines (PRIME) scheme for the treatment of PFIC. Its Pediatric
Committee has agreed to Albireo’s odevixibat Pediatric
Investigation Plan for PFIC and biliary atresia. EMA has also
granted Orphan Designation to odevixibat for the treatment of
Alagille syndrome, biliary atresia and primary biliary cholangitis.
Odevixibat has the potential to become the first approved drug
treatment for patients with PFIC. The company intends to complete
regulatory filings in the EU and U.S. for odevixibat in PFIC no
later than early 2021, in anticipation of potential regulatory
approval, issuance of a rare pediatric disease priority review
voucher and launch in the second half of 2021.
About PFIC Progressive familial intrahepatic
cholestasis (PFIC) is a rare genetic disorder that causes
progressive, life-threatening liver disease. People diagnosed with
PFIC have impaired bile flow, or cholestasis, caused by genetic
mutations. The resulting bile build-up in liver cells causes liver
disease and symptoms. The most prominent and problematic ongoing
manifestation of the disease is pruritus, or intense itching, which
often results in a severely diminished quality of life. PFIC is
also characterized by jaundice, and poor weight gain and growth. In
many cases, PFIC leads to cirrhosis and liver failure within the
first 10 years of life, and nearly all people with PFIC require
treatment before age 30. There are no drugs currently approved for
PFIC, only surgical options, including a procedure known as partial
external biliary diversion (PEBD) and liver transplantation. These
options carry substantial risks. Additional information on PFIC is
available at https://www.pficvoices.com.
About A3907A3907 is a selective inhibitor of
the apical sodium-dependent bile acid transporter (ASBT) with a
dual mechanism of action. Due to oral bioavailability, A3907 acts
on both renal and ileal transporters to increase elimination of
bile acids by both fecal and urinary excretion. This dual
inhibition approach may yield greater dosing flexibility, greater
efficacy and lower rates of adverse events associated with the
category, such as diarrhea. We expect to complete investigational
new drug enabling studies for A3907 this year and plan to advance
development in adult liver disease.
About AlbireoAlbireo Pharma is a clinical-stage
biopharmaceutical company focused on the development of novel bile
acid modulators to treat rare pediatric and adult liver diseases,
and other adult liver diseases and disorders. Albireo’s lead
product candidate, odevixibat, is being developed to treat rare
pediatric cholestatic liver diseases and is in Phase 3 development
in progressive familial intrahepatic cholestasis (PFIC) and biliary
atresia, with a third Phase 3 trial being planned in Alagille
syndrome. The Company expects to complete IND-enabling studies for
new preclinical candidate A3907 this year and plans to advance
development in adult liver disease. Albireo was spun out from
AstraZeneca in 2008 and is headquartered in Boston,
Massachusetts, with its key operating subsidiary
in Gothenburg, Sweden. The Boston Business
Journal named Albireo one of the 2020 Best Places to Work
in Massachusetts for the second consecutive year. For more
information on Albireo, please
visit www.albireopharma.com.
Forward-Looking Statements This press release
includes “forward-looking statements” within the meaning of the
Private Securities Litigation Reform Act of
1995. Forward-looking statements include statements, other
than statements of historical fact, regarding, among other things:
the plans for, or progress, scope, cost, initiation, duration,
enrollment, results or timing for availability of results of,
development of odevixibat or any other Albireo product candidate or
program, including regarding expectations regarding the impact of
COVID-19 on our business and our ability to adapt our approach as
appropriate; the Phase 3 clinical program for odevixibat in
patients with PFIC, the pivotal trial for odevixibat in biliary
atresia (BOLD), and the planned pivotal trial for odevixibat in
Alagille syndrome; the target indication(s) for development or
approval, the size, design, population, location, conduct, cost,
objective, enrollment, duration or endpoints of any clinical trial,
or the timing for initiation or completion of or availability or
reporting of results from any clinical trial, including the
long-term open-label extension study for odevixibat in PFIC, the
pivotal trial for odevixibat in biliary atresia, the planned
pivotal trial for odevixibat in Alagille syndrome; the potential
approval and commercialization of odevixibat; discussions with the
FDA or EMA regarding our programs; the potential benefits or
competitive position of odevixibat, A3907, or any other Albireo
product candidate or program or the commercial opportunity in any
target indication; the potential effects of odevixibat of the
treatment of PFIC patients and its potential to improve the current
standard of care; the potential benefits of an orphan drug
designation; the potential issuance of a rare pediatric disease
priority review voucher; or Albireo’s plans, expectations or future
operations, financial position, revenues, costs or
expenses. Albireo often uses words such as “anticipates,”
“believes,” “plans,” “expects,” “projects,” “future,” “intends,”
“may,” “will,” “should,” “could,” “estimates,” “predicts,”
“potential,” “planned,” “continue,” “guidance,” and similar
expressions to identify forward-looking statements. Actual results,
performance or experience may differ materially from those
expressed or implied by any forward-looking statement as a result
of various risks, uncertainties and other factors, including, but
not limited to: negative impacts of the COVID-19 pandemic,
including on manufacturing, supply, conduct or initiation of
clinical trials, or other aspects of our business; whether
favorable findings from clinical trials of odevixibat to date,
including findings in indications other than PFIC, will be
predictive of results from other clinical trials of odevixibat;
whether either or both of the FDA and EMA will determine
that the primary endpoint for their respective evaluations and
treatment duration of the double-blind Phase 3 trial in patients
with PFIC are sufficient to support approval of odevixibat
in the United States or the European Union, to treat
PFIC, a symptom of PFIC, a specific PFIC subtype(s) or otherwise;
the outcome and interpretation by regulatory authorities of the
ongoing third-party study pooling and analyzing of long-term PFIC
patient data; the timing for initiation or completion of, or for
availability of data from, clinical trials of odevixibat, including
the pivotal program in biliary atresia or the planned pivotal
program in Alagille syndrome, and the outcomes of such trials;
Albireo’s ability to obtain coverage, pricing or reimbursement for
approved products in the United States or European
Union; delays or other challenges in the recruitment of patients
for, or the conduct of, company’s clinical trials; and Albireo’s
critical accounting policies. These and other risks and
uncertainties that Albireo faces are described in greater detail
under the heading “Risk Factors” in Albireo’s most recent Annual
Report on Form 10-K or in subsequent filings that it makes with
the Securities and Exchange Commission. As a result of risks
and uncertainties that Albireo faces, the results or events
indicated by any forward-looking statement may not occur. Albireo
cautions you not to place undue reliance on any forward-looking
statement. In addition, any forward-looking statement in this press
release represents Albireo’s views only as of the date of this
press release and should not be relied upon as representing its
views as of any subsequent date. Albireo disclaims any obligation
to update any forward-looking statement, except as required by
applicable law.
Media Contact:Colleen Alabiso,
857-356-3905, colleen.alabiso@albireopharma.comLisa Rivero,
617-947-0899, lisa.rivero@syneoshealth.com
Investor Contact: Hans Vitzthum, LifeSci
Advisors, LLC., 857-272-6177
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