Ipsen receives CHMP positive opinions for Iqirvo® (elafibranor) in
Primary Biliary Cholangitis and Kayfanda® (odevixibat) in Alagille
Syndrome, two rare cholestatic liver diseases
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 PBC
PBC 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 ASSERT
ASSERT2 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
- Craig
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
Disclaimers and/or Forward-Looking
Statements
The forward-looking statements, objectives and targets contained
herein are based on Ipsen’s management strategy, current views and
assumptions. Such statements involve known and unknown risks and
uncertainties that may cause actual results, performance or events
to differ materially from those anticipated herein. All of the
above risks could affect Ipsen’s future ability to achieve its
financial targets, which were set assuming reasonable macroeconomic
conditions based on the information available today. Use of the
words ‘believes’, ‘anticipates’ and ‘expects’ and similar
expressions are intended to identify forward-looking statements,
including Ipsen’s expectations regarding future events, including
regulatory filings and determinations. Moreover, the targets
described in this document were prepared without taking into
account external-growth assumptions and potential future
acquisitions, which may alter these parameters. These objectives
are based on data and assumptions regarded as reasonable by Ipsen.
These targets depend on conditions or facts likely to happen in the
future, and not exclusively on historical data. Actual results may
depart significantly from these targets given the occurrence of
certain risks and uncertainties, notably the fact that a promising
medicine in early development phase or clinical trial may end up
never being launched on the market or reaching its commercial
targets, notably for regulatory or competition reasons. Ipsen must
face or might face competition from generic medicine that might
translate into a loss of market share. Furthermore, the research
and development process involves several stages each of which
involves the substantial risk that Ipsen may fail to achieve its
objectives and be forced to abandon its efforts with regards to a
medicine in which it has invested significant sums. Therefore,
Ipsen cannot be certain that favorable results obtained during
preclinical trials will be confirmed subsequently during clinical
trials, or that the results of clinical trials will be sufficient
to demonstrate the safe and effective nature of the medicine
concerned. There can be no guarantees a medicine will receive the
necessary regulatory approvals or that the medicine will prove to
be commercially successful. If underlying assumptions prove
inaccurate or risks or uncertainties materialize, actual results
may differ materially from those set forth in the forward-looking
statements. Other risks and uncertainties include but are not
limited to, general industry conditions and competition; general
economic factors, including interest rate and currency exchange
rate fluctuations; the impact of pharmaceutical industry regulation
and healthcare legislation; global trends toward healthcare cost
containment; technological advances, new medicine and patents
attained by competitors; challenges inherent in new-medicine
development, including obtaining regulatory approval; Ipsen’s
ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the
effectiveness of Ipsen’s patents and other protections for
innovative medicines; and the exposure to litigation, including
patent litigation, and/or regulatory actions. Ipsen also depends on
third parties to develop and market some of its medicines which
could potentially generate substantial royalties; these partners
could behave in such ways which could cause damage to Ipsen’s
activities and financial results. Ipsen cannot be certain that its
partners will fulfil their obligations. It might be unable to
obtain any benefit from those agreements. A default by any of
Ipsen’s partners could generate lower revenues than expected. Such
situations could have a negative impact on Ipsen’s business,
financial position or performance. Ipsen expressly disclaims any
obligation or undertaking to update or revise any forward-looking
statements, targets or estimates contained in this press release to
reflect any change in events, conditions, assumptions or
circumstances on which any such statements are based, unless so
required by applicable law. Ipsen’s business is subject to the risk
factors outlined in its registration documents filed with the
French Autorité des Marchés Financiers. The risks and
uncertainties set out are not exhaustive and the reader is advised
to refer to Ipsen’s latest Universal Registration Document,
available on ipsen.com.
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
Ipsen (EU:IPN)
Gráfica de Acción Histórica
De Jun 2024 a Jul 2024
Ipsen (EU:IPN)
Gráfica de Acción Histórica
De Jul 2023 a Jul 2024