Ipsen receives CHMP positive opinions
for Iqirvo® (elafibranor) in
Primary Biliary Cholangitis and Kayfanda®
(odevixibat) in Alagille Syndrome, two rare cholestatic
liver diseases
- CHMP
positive opinion for Iqirvo®
(elafibranor) recommended for the treatment of primary
biliary cholangitis, following FDA approval in June
2024
- CHMP
positive opinion for Kayfanda®
(odevixibat) recommended for cholestatic pruritus in
patients with Alagille syndrome
- Final
European Commission decision for both medicines expected in Q3
2024
- Ipsen
continues to build leading rare cholestatic liver disease portfolio
with these two new indications anticipated for approval in
Europe
PARIS, FRANCE, 26 July 2024 -
Ipsen (Euronext: IPN; ADR: IPSEY) announced today two positive
opinions by the European Medicines Agency’s (EMA) Committee for
Medicinal Products for Human Use (CHMP) for two different rare
cholestatic liver disease medicines from the company’s growing
portfolio. Iqirvo® (elafibranor) has been recommended for the
treatment of primary biliary cholangitis (PBC) in combination with
ursodeoxycholic acid (UDCA) in adults with an inadequate response
to UDCA or as a monotherapy in patients unable to tolerate UDCA.
Kayfanda® (odevixibat) has also received a positive opinion from
CHMP as a treatment of cholestatic pruritus in Alagille syndrome
(ALGS) in patients aged 6 months or older. The European Commission
will now consider the CHMP recommendations. Final decisions on
marketing authorization for Iqirvo and for Kayfanda are anticipated
in Q3, 2024.
“We are delighted to have received CHMP positive
opinions for two potential new medicines in rare cholestatic liver
diseases, on the same day. A rare achievement, and one that
demonstrates our commitment to addressing the unmet medical needs
in these diseases, said Christelle Huguet, Executive Vice
President, Head of R&D. “PBC can progress to liver damage and
even liver failure without effective therapies. Today’s decision
takes us closer to being able to offer Iqirvo as a new treatment
for patients, which significantly improves biomarkers that predict
disease progression, without worsening symptoms. Also, with the
positive opinion for Kayfanda we are moving forward in our efforts
to provide a new treatment option for children with Alagille
Syndrome, whose liver health can deteriorate rapidly and who often
endure a very poor quality of life.”
Iqirvo and PBC
Iqirvo is a first-in-class, oral, peroxisome
proliferator-activated receptor (PPAR) agonist. Iqirvo was
in-licensed by Ipsen from Genfit in 2021. The CHMP positive opinion
is based mainly on data from the Phase III ELATIVE trial. The
composite endpoint was achieved with results demonstrating
statistically significant improvements in alkaline phosphatase
(ALP) and total bilirubin (TB), biomarkers of PBC disease
progression. For the key secondary endpoint using the PBC Worst
Itch NRS score a trend towards improvement in pruritus (itch) was
observed for elafibranor versus placebo, which was not
statistically significant. Two other secondary
patient-reported outcome measures were used to assess itch, and
greater reductions were observed with Iqirvo compared with placebo
at Week 52, according to the itch domain of PBC-40 quality of life
questionnaire (LS mean difference -2.3; 95% CI, -4.0 to -0.7) and
5-D Itch total score (LS mean difference, -3.0; 95% CI, -5.5 to
-0.5).1
“PBC is a progressive disease with a high number
of patients who either don’t respond or can’t tolerate the current
available treatments. This can result in ongoing disease
progression, which may not be picked up until the patient’s next
doctor’s appointment, which can be as long as 12 months between
visits in some cases,” said Professor Marco Carbone, Professor of
Gastroenterology, University of Milano-Bicocca and Consultant
Hepatologist, the Niguarda Liver Transplant Centre, Milan. “It is
important that we not only regularly review our PBC patients to
ensure the levels of alkaline phosphatase, or ALP, and bilirubin
are within normal limits, but that we also discuss symptoms that
might impair patients’ quality of life potentially leading to
withdrawal from current treatments.”
“It is helpful for people diagnosed with PBC to
understand that disease progression is monitored through levels of
biomarkers in the blood, such as ALP,” said Patient Advocate, Mrs
Sindee Weinbaum from European Liver Patients’ Association. “Being
aware of these levels helps the person living with PBC to be more
in control of their condition and to have constructive
conversations with their doctor about how to control their symptoms
and about what treatment is right for them. This is important for
people living with PBC who can sometimes feel unheard.”
Kayfanda and Alagille
Syndrome
Kayfanda’s CHMP positive opinion is based on the
ASSERT Phase III clinical trial data, presented at the 2022
American Association for the Study of Liver Disease (AASLD)
congress and recently published in Lancet Gastroenterology &
Hepatology.2 ASSERT is the world’s first and only Phase III trial
completed in patients with ALGS. The data demonstrated efficacy of
odevixibat in pruritus, a measure of treatment benefit, based on
the worst scratching score using an observer-reported outcome
instrument. Results demonstrated statistically significant and
clinically meaningful improvements from baseline to month 6, in
scratching severity, for odevixibat versus placebo, which was seen
rapidly and maintained over the study period.
“Effective and well-tolerated treatments that
can manage the debilitating itch caused by Alagille Syndrome and
reduce the concentration of bile acids in the blood, are of great
importance in our management and care of children with this
condition and it is a positive development that there may soon be a
new treatment option available,” said Professor Henkjan Verkade,
Pediatric Gastroenterology and Hepatology, Department of
Pediatrics, University of Groningen, Beatrix Children's Hospital
and University Medical Center Groningen, Netherlands. “This
condition leads to multiple complications, it is however the
intense itch experienced by these children and resulting sleep
disturbances that is reported by the vast majority of people living
with and caring for a child with liver disease due to Alagille
Syndrome, as being the most significant.”
In the ASSERT trial efficacy was also
demonstrated on the key secondary endpoint showing a statistically
significant reduction in serum bile acid concentration at the end
of treatment for patients on odevixibat compared to placebo.
Consistent with the improvements observed in pruritus, treatment
with odevixibat led to significant improvements in multiple
observer-reported outcome sleep parameters. The overall incidence
of treatment emergent adverse events with odevixibat was similar to
placebo, with a low drug-related diarrhea rate in patients with
ALGS. All patients completed the study and 50 out of 52 patients
have joined the extension study with all receiving odevixibat.2
ENDS
About PBCPBC is a rare,
autoimmune, cholestatic liver disease, affecting approximately nine
women for every one man. A build-up of bile and toxins
(cholestasis) and chronic inflammation causes fibrosis (scarring)
of the liver and destruction of the bile ducts. It is a life-long
condition that can worsen over time if not effectively treated,
leading to liver transplant and in some cases, premature death. PBC
impacts patients’ daily lives through debilitating symptoms
including most commonly pruritus and fatigue. Currently, there are
no approved treatments available that can effectively manage both
disease progression and life-impacting symptoms.
About Iqirvo®
(elafibranor) Iqirvo® (pronounced EYE-KER-VO) is
an oral, once-daily, peroxisome proliferator-activated receptor
(PPAR) agonist, which exerts an effect on PPARα and PPARδ, which
are thought to be key regulators of bile acid (BA) homeostasis,
inflammation and fibrosis. Pharmacological activity that is
potentially relevant to Iqirvo therapeutic effects includes
inhibition of bile acid synthesis through activation of PPARα and
PPARδ. The proposed indication is for the treatment of primary
biliary cholangitis (PBC) in combination with ursodeoxycholic acid
(UDCA) in adults who have an inadequate response to UDCA, or as
monotherapy in patients unable to tolerate UDCA. In 2019, Iqirvo
was granted Breakthrough Therapy Designation by the U.S Food and
Drug Administration (FDA) in adults with PBC who have an inadequate
response to ursodeoxycholic acid (UDCA). UCDA being the existing
first-line therapy for PBC. Iqirvo has not received approval by
regulatory authorities outside of the U.S. Iqirvo is currently
under regulatory review awaiting a final decision from the European
Commission. It is also in regulatory processes with other
authorities including the UK Medicines and Healthcare products
Regulatory Agency (MHRA). Iqirvo (elafibranor) was discovered and
developed by Genfit and Ipsen licensed the exclusive worldwide
rights (except China, Hong Kong, Taiwan and Macau) to elafibranor
from Genfit in 2021.
About ELATIVE ELATIVE1 is a
multi-center, randomized, double-blind, placebo-controlled Phase
III clinical trial, with an open-label long-term extension
(NCT04526665). ELATIVE evaluated the efficacy and safety of
elafibranor 80mg once daily versus placebo for the treatment of
patients with PBC with an inadequate response or intolerance to
ursodeoxycholic acid (UDCA), the existing first-line therapy for
PBC. The trial enrolled 161 patients who were randomized 2:1 to
receive elafibranor 80mg once daily or placebo. Patients with an
inadequate response to UDCA would continue to receive UDCA in
combination with elafibranor or placebo, while patients unable to
tolerate UDCA would receive only elafibranor or placebo. Patients
continued their assigned treatment after Week 52 until all patients
had completed their treatment or for a maximum of 104 weeks. Data
was also collected during this period, and additional analyses were
conducted with a focus on Week 78.
In the trial, results show statistically
significant improvements in the primary composite endpoint of
biochemical response, defined as alkaline phosphatase (ALP)
<1.67 x upper limit of normal (ULN), an ALP decrease ≥ 15
percent and total bilirubin (TB) ≤ ULN at 52 weeks, with a
significant treatment benefit demonstrating a 47% placebo-adjusted
difference (P<0.001) between patients on elafibranor 80mg (51%)
compared with patients on placebo (4%) achieving a biochemical
response. ALP and bilirubin are important predictors of PBC disease
progression. Reductions in levels of both can indicate reduced
cholestatic injury and improved liver function.
Only patients receiving elafibranor achieved
normalization of ALP (upper limit of normal 104 U/L in females and
129 U/L in males) at Week 52 (15% vs 0% placebo, P=0.002), a key
secondary endpoint of the trial. The significant biochemical effect
of elafibranor measured by ALP reduction was further supported by
data demonstrating reductions from baseline in ALP levels were
rapid, seen as early as Week 4 in the elafibranor group, and were
sustained through Week 52, with a decrease in ALP of 41% on
elafibranor compared with placebo.
Elafibranor was well tolerated in the trial.
Similar percentages of patients in the treatment group and the
placebo group experienced adverse events, treatment-related adverse
events, severe or serious adverse events or adverse events leading
to discontinuation. Adverse events occurring in >10% of patients
and more frequently on elafibranor versus placebo included
abdominal pain, diarrhea, nausea, and vomiting.
About ALGS ALGS is an inherited
rare, genetic disorder that can affect multiple organs including
the liver, heart, skeleton, eyes and kidneys. Liver damage may
result from having fewer than normal, narrowed or malformed bile
ducts, which leads to a build-up of toxic bile acid, known as
cholestasis and this in turn can cause fibrosis and progressive
liver disease. Approximately 95% of patients with the condition
present with chronic cholestasis, usually within the first three
months of life and as many as 88% also present with severe,
intractable pruritus or itch. The estimated global incidence of
ALGS is 3 in 100,000 live births.
About Kayfanda®
(odevixibat)Kaydanda® (odevixibat) is a once-daily
non-systemic ileal bile acid transport (IBAT) inhibitor being
investigated in the E.U. for the treatment of cholestatic pruritus
in Alagille syndrome (ALGS) in patients aged 6 months or older.
Odevixibat was approved in June 2021 in the E.U. under the brand
name Bylvay ®, as the first drug treatment option for all types of
progressive familial intrahepatic cholestasis (PFIC) in patients
aged 6 months or older, and in the U.S. under the brand name
Bylvay®, as the first drug treatment option for patients 3 months
of age and older living with cholestatic pruritus due to PFIC.
Bylvay has received orphan exclusivity for the treatment of PFIC in
the E.U. and in the U.S. In June 2023 Bylvay was approved in the
U.S. for the treatment of cholestatic pruritus in patients from 12
months of age with ALGS and received orphan exclusivity for ALGS.
In October 2023, while the EMA’s CHMP recommended the approval of
Bylvay in ALGS, the EMA’s Committee for Orphan Medicinal Products
(COMP) recommended not to maintain orphan exclusivity in the E.U.
for Bylvay in ALGS. In order to ensure sustainable access and
availability for Bylvay in the approved indication for the
treatment of PFIC, which is supported by orphan drug status,
odevixibat for the treatment of ALGS has been resubmitted to the
EMA under a new brand name, Kayfanda, without orphan designation
and is currently awaiting a final decision from the European
Commission.
About ASSERTASSERT2 is a
double-blind, randomized, placebo-controlled trial designed to
evaluate the safety and efficacy of 120 µg/kg/day Bylvay
(odevixibat) for 24 weeks in relieving pruritus in patients with
ALGS conducted in 52 patients with 32 sites across North
America, Europe, Middle East, and Asia Pacific.
The trial enrolled patients aged 0 to 17 years
of age with a genetically confirmed diagnosis of ALGS. In the
primary analysis, the study met the primary endpoint showing highly
statistically significant improvement in pruritus for patients on
odevixibat as measured by the PRUCISION Observer-Reported Outcome
scratching score (0-4 point scale), from baseline at month 6 (weeks
21 to 24), compared to the placebo arm (p=0.002). More than 90% of
patients were pruritus responders (≥ 1 point change at any time
during 24 weeks).
The study also met the key secondary endpoint
showing a highly statistically significant reduction in serum bile
acid concentration from baseline to the average of weeks 20 and 24
(compared to the placebo arm p=0.001). Statistically significant
improvements in multiple sleep parameters were observed as early as
weeks 1-4 compared to patients on placebo with continued
improvement through week 24.
In the study, there were no patient
discontinuations and 96% of patients rolled over into the
open-label extension study. Bylvay had an overall adverse event
incidence similar to placebo and a low incidence of drug-related
diarrhea (11.4% vs. 5.9% placebo).
The detailed recommendations for the use of
odevixibat are described in the Summary of Product
Characteristics (EU SmPC) and U.S. Prescribing
Information (USPI)
About Ipsen
We are a global biopharmaceutical company with a
focus on bringing transformative medicines to patients in three
therapeutic areas: Oncology, Rare Disease and Neuroscience.
Our pipeline is fuelled by external innovation
and supported by nearly 100 years of development experience and
global hubs in the U.S., France and the U.K. Our teams in more than
40 countries and our partnerships around the world enable us to
bring medicines to patients in more than 80 countries.
Ipsen is listed in Paris (Euronext: IPN) and in
the U.S. through a Sponsored Level I American Depositary Receipt
program (ADR: IPSEY). For more information, visit ipsen.com.
Ipsen contacts
Investors
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Marks | + 44 (0)7584 34 91 93 | craig.marks@ipsen.com
- Nicolas
Bogler | + 33 6 52 19 98 92 |
nicolas.bogler@ipsen.com
Media
- Amy Wolf
| + 41 79 576 07 23 | amy.wolf@ipsen.com
- Anna
Gibbins | + 44 7717 80 19 00| anna.gibbins@ipsen.com
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References
- Kowdley. K.V, et al. Efficacy and
Safety of Elafibranor in Primary Biliary Cholangitis. NEJM. 2023.
DOI: 10.1056/NEJMoa2306185
- Ovchinsky N., et al. Efficacy and
safety of odevixibat in patients with Alagille syndrome (ASSRT); a
phase 3, double-blind, randomized, placebo-controlled trial. Lancet
Gastroenterol / Hepatol. 2024
doi.org/10.1016/S2468-1253(24)00074-8
- PR_CHMP_Iqirvo and Kayfanda_260724
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