* Positive opinion from Committee for Medicinal Products for Human Use (CHMP)
based on Bylvay Phase III ASSERT clinical-trial data in Alagille syndrome
(ALGS)
* Negative opinion from Committee for Orphan Medicinal Products (COMP)
recommending not to maintain orphan drug designation for treatment of ALGS
* Ipsen to appeal negative COMP opinion, which might delay final European
Commission decision
* Approval already granted by U.S. FDA in June 2023 for the treatment of
cholestatic pruritus in patients with ALGS aged 12 months and older
PARIS, FRANCE, 21 July 2023 - Ipsen (Euronext: IPN: ADR: IPSEY) today announced
that the European Medicines Agency's (EMA) Committee for Medicinal Products for
Human Use (CHMP) has issued a positive opinion recommending the approval of
Bylvay(®) (odevixibat) for the treatment of cholestatic pruritus in patients
with Alagille syndrome (ALGS) aged six months or older.
"We are pleased with today's CHMP positive opinion which is supported by the
data from our Phase III ASSERT trial," said Howard Mayer, Executive Vice
President and Head of Research and Development for Ipsen. "These children endure
a very poor quality of life. The severe itching, known as pruritus, caused by
the back-up of bile acids in the liver and bloodstream of individuals living
with Alagille syndrome, sometimes results in scratching so hard it leads to
broken skin. We are committed to bringing a much-needed additional drug
treatment option to Alagille patients and families in the E.U."
The Committee for Orphan Medicinal Products (COMP), a scientific committee of
the EMA, has concurrently issued a negative opinion for the maintenance of
Bylvay's orphan drug designation in ALGS.
This negative COMP opinion prevents the retention of orphan-drug status in
Bylvay's marketing authorization in ALGS and might delay a final European
Commission decision. Ipsen plans to submit an appeal in respect of the COMP
opinion.
Bylvay, is an orphan medicine already approved in the E.U. for the treatment of
progressive familial intrahepatic cholestasis (PFIC) in patients aged six months
or older. In November 2022, a variation application to the current market
authorization was submitted. The application sought approval in the E.U. for a
second orphan indication for Bylvay, the treatment of pruritus in patients with
ALGS. In 2012, Bylvay received orphan designation for the treatment of ALGS in
the E.U., which supported the development of Bylvay through preclinical and
clinical stages.
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 (ESPGHAN) 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 was approved in 2021 in the U.S. as the first medicine-treatment option
for patients three months of age and 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 was also approved in the U.S. for the treatment of
cholestatic pruritus in patients from 12 months of age with ALGS.
Bylvay has received orphan exclusivity for the treatment of PFIC, and orphan
drug designations for the treatment of ALGS and biliary atresia, in the U.S. and
the E.U. In a potential future third indication, the rare pediatric cholestatic
liver disease, biliary atresia, Bylvay is in late-stage development with the
Phase III BOLD trial.
ENDS
About Bylvay(®) (odevixibat)
Bylvay is a potent, once-daily, non-systemic ileal bile acid transport inhibitor
(IBATi) 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 and 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 is also approved 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
(https://www.ema.europa.eu/en/documents/product-information/bylvay-epar-product-
information_en.pdf), INN- (https://www.ema.europa.eu/en/documents/product-
information/bylvay-epar-product-information_en.pdf)odevixibat
(https://www.ema.europa.eu/en/documents/product-information/bylvay-epar-product-
information_en.pdf) (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.
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 three
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.
ASSERT Phase III clinical trial data
ASSERT is 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, 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 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 week 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).
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)
On March 3(rd), 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 Communications Senior Manager
+1 (347) 401-8583 Global Media Relations
+33 6 69 09 12 96
Amy Wolf
VP, Head of Corporate Brand Strategy &
Communications
+41 79 576 07 23
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