* Positive opinion from Committee for Medicinal Products for Human Use
recommending approval of Bylvay(®) (odevixibat) based on Phase III ASSERT
clinical-trial data in Alagille syndrome (ALGS) already received in July
2023
* Committee for Orphan Medicinal Products confirms a negative opinion of its
review recommending not to maintain the orphan designation for Bylvay in
ALGS
* Ipsen plans to submit a new Marketing Authorisation Application for the
treatment of ALGS by the end of 2023 under a new brand name
PARIS, FRANCE, 23 October 2023 - Ipsen (Euronext: IPN: ADR: IPSEY) today
announced that the European Medicines Agency's (EMA) Committee for Orphan
Medicinal Products (COMP) confirmed its negative opinion recommending not to
maintain the orphan designation for Bylvay(®) (odevixibat) in Alagille syndrome
(ALGS). This is despite a positive opinion from the Committee for Medicinal
Products for Human Use (CHMP) in July 2023. Orphan designation has a strong
influence on the reimbursement mechanisms and access for patients to medicines
in some countries in the E.U. In order to maintain Bylvay's orphan designation
in the approved treatment of progressive familial intrahepatic cholestasis
(PFIC), Ipsen is planning to resubmit to the EMA under a new brand name for the
treatment of ALGS by the end of 2023.
"We stand by our commitment to bring as soon as possible a much-needed treatment
option to patients with Alagille syndrome and their families in the E.U., as we
believe in the potential benefit this medicine could provide to the Alagille
community," said Christelle Huguet, Executive Vice President and Head of
Research and Development for Ipsen. "We are disappointed with the opinion of the
COMP as the Orphan Medicinal Product Regulation aims to stimulate research and
development for rare diseases. The current approach to assessing "significant
benefit" threatens to undermine the aims of this Regulation."
The CHMP and COMP reviewed data from the Bylvay clinical-trial program,
including ASSERT, a double-blind, randomized, placebo-controlled Phase III,
multi-center efficacy and safety trial conducted in ALGS. Positive data from
ASSERT, presented at the 2023 European Society for Pediatric Gastroenterology
Hepatology and Nutrition congress, demonstrated that Bylvay provided highly
statistically significant and clinically meaningful improvements in pruritus,
starting as early as one week after initiation of treatment and were sustained
over the 24 weeks of the trial. More than 90% of patients were pruritus
responders (>= one point change at any time during 24 weeks). The overall
incidence of treatment-emergent adverse events was similar to placebo. No
patients discontinued the trial, and 96% of patients rolled over into the open-
label extension trial.
Bylvay received regulatory approval in 2021 in the U.S. as the first medicine-
treatment option for patients aged three months or older living with cholestatic
pruritus due to PFIC, and for the treatment of PFIC in patients aged six months
or older in the E.U. In June 2023, Bylvay also received regulatory approval in
the U.S. for the treatment of cholestatic pruritus in patients aged 12 months or
older with ALGS.
Bylvay received orphan exclusivity for the treatment of PFIC in the U.S. and the
E.U. Bylvay also received orphan designation for the treatment of ALGS in the
U.S. and the E.U. In a potential future third indication under development, the
rare pediatric cholestatic liver disease biliary atresia, Bylvay received orphan
designation in the U.S. and the E.U. and is in late-stage development with the
Phase III BOLD trial.
ENDS
ASSERT Phase III clinical trial data?
ASSERT was a double-blind, randomized, placebo-controlled trial designed to
evaluate the safety and efficacy of 120 µg /kg/day Bylvay for 24 weeks in
relieving pruritus in patients with ALGS with 32 sites across North
America, Europe, the Middle East, and Asia Pacific. The trial enrolled patients
aged 0 to 17 years with a genetically confirmed diagnosis of ALGS. In the
primary analysis, the trial met the primary endpoint showing highly
statistically significant improvement in pruritus 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 the
24 weeks). The trial 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 week 1-4 compared to patients on placebo with
continued improvement through week 24. In the trial, there were no patient
discontinuations and 96% of patients rolled over into the open-label extension
trial. Bylvay had an overall adverse event incidence similar to placebo and a
low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo).
About Bylvay(®) (odevixibat)
Bylvay is a potent, once-daily, non-systemic ileal bile acid transport inhibitor
that acts locally in the small intestine and has minimal systemic exposure. It
is approved in the U.S. for the treatment of pruritus in patients three months
of age or older with PFIC, where it has orphan exclusivity. Bylvay was first
launched as a treatment option for patients with PFIC in the U.S. in 2021, where
it is supported by a program designed to assist with access to treatment and
patient support. Bylvay also received regulatory approval in the E.U. for the
treatment of PFIC in patients aged six months or older. It has launched in over
nine countries and has secured public reimbursement across several major markets
including Germany, Italy, the U.K., France and Belgium. In June 2023, Bylvay was
also approved in the U.S. for the treatment of cholestatic pruritus in patients
from 12 months of age with Alagille syndrome.??
?
View full U.S. prescribing information here: ipsen.com
(https://www.ipsen.com/websites/Ipsen_Online/wp-
content/uploads/sites/9/2023/06/13165353/Bylvay-USPI-06-2023.pdf)?
View full E.U. prescribing information here: Bylvay, INN-odevixibat (europa.eu)
(https://www.ema.europa.eu/en/documents/product-information/bylvay-epar-product-
information_en.pdf)?
?
Important Safety Information??
* PFIC: The most common adverse reactions are diarrhea, liver test
abnormalities, vomiting, abdominal pain, and fat-soluble vitamin
deficiency.
* ALGS: The most common adverse reactions are diarrhea, abdominal pain,
hematoma, and weight decrease.
* Liver Test Abnormalities: Patients should obtain baseline liver tests and
monitor during treatment. Dose reduction or treatment interruption may be
required if abnormalities occur. For persistent or recurrent liver test
abnormalities, consider treatment discontinuation.
* Diarrhea: Treat dehydration. Treatment interruption or discontinuation may
be required for persistent diarrhea.
* Fat-Soluble Vitamin (FSV) Deficiency: Patient should obtain baseline vitamin
levels and monitor during treatment. Supplement if deficiency is observed.
If FSV deficiency persists or worsens despite FSV supplementation,
discontinue treatment.
About Alagille syndrome (ALGS)
ALGS is an inherited rare, genetic disorder that can affect multiple organ
systems in the body 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 toxic bile acid build-up, which in turn can cause
scarring and progressive liver disease. Approximately 95% of patients with the
condition present with chronic cholestasis, usually within the first few months
of life and as many as 88% also present with severe, intractable pruritus. The
estimated global incidence of ALGS is 3 in 100,000 live births. Currently in the
U.S., it is estimated that there are 1,300 patients who may be eligible for
IBATi treatment.
About Ipsen??
Ipsen is a global, mid-sized biopharmaceutical company focused on transformative
medicines in Oncology, Rare Disease and Neuroscience. With total sales of EUR3.0bn
in FY 2022, Ipsen sells medicines in over 100?countries. Alongside its external-
innovation strategy, the Company's research and development efforts are focused
on its innovative and differentiated technological platforms located in the
heart of leading biotechnological and life-science hubs: Paris-Saclay, France;
Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has around 5,400
colleagues worldwide and 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 (https://www.ipsen.com/)?
?
In March 2023, Ipsen completed the acquisition of Albireo Pharma Inc,?a leading
innovator in bile-acid modulators to treat rare liver conditions, and the
marketing authorization holder of Bylvay.????
For further information:??
Ipsen Contacts?
Investors?
Craig Marks? Nicolas Bogler?
Vice President, Investor Relations? Investor Relations Manager?
+44 (0)7584 349 193? +33 6 52 19 98 92?
? ?
Media?
Jennifer Moore? Ioana Piscociu?
Senior Director, Global Corporate Senior Manager, Global Media
Communications? Relations?
+1 (347) 401-8583? +33 6 69 09 12 96?
?
Amy Wolf? ?
VP, Head of Corporate Brand Strategy &
Communications?
+41 79 576 07 23?
?
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