Ipsen receives CHMP constructive opinions for Iqirvo® (elafibranor) in Major Biliary Cholangitis and Kayfanda® (odevixibat) in Alagille Syndrome, two uncommon cholestatic liver ailments

Article content material

Ipsen receives CHMP constructive opinions for Iqirvo^® (elafibranor) in Major Biliary Cholangitis and Kayfanda^® (odevixibat) in Alagille Syndrome, two uncommon cholestatic liver ailments

• CHMP constructive opinion for Iqirvo^® (elafibranor) beneficial for the therapy of main biliary cholangitis, following FDA approval in June 2024
• CHMP constructive opinion for Kayfanda^® (odevixibat) beneficial for cholestatic pruritus in sufferers with Alagille syndrome
• Ultimate European Fee resolution for each medicines anticipated in Q3 2024
• Ipsen continues to construct main uncommon cholestatic liver illness portfolio with these two new indications anticipated for approval in Europe

Article content material

PARIS, FRANCE, 26 July 2024 – Ipsen (Euronext: IPN; ADR: IPSEY) introduced at this time two constructive opinions by the European Medicines Company’s (EMA) Committee for Medicinal Merchandise for Human Use (CHMP) for 2 completely different uncommon cholestatic liver illness medicines from the corporate’s rising portfolio. Iqirvo^® (elafibranor) has been beneficial for the therapy of main biliary cholangitis (PBC) together with ursodeoxycholic acid (UDCA) in adults with an insufficient response to UDCA or as a monotherapy in sufferers unable to tolerate UDCA. Kayfanda^® (odevixibat) has additionally acquired a constructive opinion from CHMP as a therapy of cholestatic pruritus in Alagille syndrome (ALGS) in sufferers aged 6 months or older. The European Fee will now take into account the CHMP suggestions. Ultimate choices on advertising and marketing authorization for Iqirvo and for Kayfanda are anticipated in Q3, 2024.

“We’re delighted to have acquired CHMP constructive opinions for 2 potential new medicines in uncommon cholestatic liver ailments, on the identical day. A uncommon achievement, and one which demonstrates our dedication to addressing the unmet medical wants in these ailments, stated Christelle Huguet, Government Vice President, Head of R&D. “PBC can progress to liver injury and even liver failure with out efficient therapies. At present’s resolution takes us nearer to with the ability to supply Iqirvo as a brand new therapy for sufferers, which considerably improves biomarkers that predict illness development, with out worsening signs. Additionally, with the constructive opinion for Kayfanda we’re transferring ahead in our efforts to supply a brand new therapy possibility for youngsters with Alagille Syndrome, whose liver well being can deteriorate quickly and who typically endure a really poor high quality of life.”

Article content material

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 constructive opinion is predicated primarily on knowledge from the Part III ELATIVE trial. The composite endpoint was achieved with outcomes demonstrating statistically vital enhancements in alkaline phosphatase (ALP) and complete bilirubin (TB), biomarkers of PBC illness development. For the important thing secondary endpoint utilizing the PBC Worst Itch NRS rating a development in direction of enchancment in pruritus (itch) was noticed for elafibranor versus placebo, which was not statistically vital. Two different secondary patient-reported consequence measures had been used to evaluate itch, and larger reductions had been noticed with Iqirvo in contrast with placebo at Week 52, in keeping with the itch area of PBC-40 high quality of life questionnaire (LS imply distinction -2.3; 95% CI, -4.0 to -0.7) and 5-D Itch complete rating (LS imply distinction, -3.0; 95% CI, -5.5 to -0.5).¹

“PBC is a progressive illness with a excessive variety of sufferers who both don’t reply or can’t tolerate the present obtainable remedies. This can lead to ongoing illness development, which is probably not picked up till the affected person’s subsequent physician’s appointment, which might be so long as 12 months between visits in some circumstances,” stated Professor Marco Carbone, Professor of Gastroenterology, College of Milano-Bicocca and Guide Hepatologist, the Niguarda Liver Transplant Centre, Milan. “It will be important that we not solely repeatedly assessment our PBC sufferers to make sure the degrees of alkaline phosphatase, or ALP, and bilirubin are inside regular limits, however that we additionally focus on signs which may impair sufferers’ high quality of life probably resulting in withdrawal from present remedies.”  

Article content material

Article content material

“It’s useful for folks recognized with PBC to know that illness development is monitored by means of ranges of biomarkers within the blood, equivalent to ALP,” stated Affected person Advocate, Mrs Sindee Weinbaum from European Liver Sufferers’ Affiliation. “Being conscious of those ranges helps the individual dwelling with PBC to be extra in command of their situation and to have constructive conversations with their physician about methods to management their signs and about what therapy is correct for them. That is vital for folks dwelling with PBC who can typically really feel unheard.”

Kayfanda and Alagille Syndrome

Kayfanda’s CHMP constructive opinion is predicated on the ASSERT Part III medical trial knowledge, introduced on the 2022 American Affiliation for the Research of Liver Illness (AASLD) congress and lately printed in Lancet Gastroenterology & Hepatology.² ASSERT is the world’s first and solely Part III trial accomplished in sufferers with ALGS. The information demonstrated efficacy of odevixibat in pruritus, a measure of therapy profit, based mostly on the worst scratching rating utilizing an observer-reported consequence instrument. Outcomes demonstrated statistically vital and clinically significant enhancements from baseline to month 6, in scratching severity, for odevixibat versus placebo, which was seen quickly and maintained over the research interval.

Article content material

“Efficient and well-tolerated remedies that may handle the debilitating itch attributable to Alagille Syndrome and scale back the focus of bile acids within the blood, are of nice significance in our administration and care of youngsters with this situation and it’s a constructive improvement that there could quickly be a brand new therapy possibility obtainable,” stated Professor Henkjan Verkade, Pediatric Gastroenterology and Hepatology, Division of Pediatrics, College of Groningen, Beatrix Kids’s Hospital and College Medical Heart Groningen, Netherlands. “This situation results in a number of problems, it’s nevertheless the extreme itch skilled by these kids and ensuing sleep disturbances that’s reported by the overwhelming majority of individuals dwelling with and caring for a kid with liver illness resulting from Alagille Syndrome, as being essentially the most vital.”  

Within the ASSERT trial efficacy was additionally demonstrated on the important thing secondary endpoint exhibiting a statistically vital discount in serum bile acid focus on the finish of therapy for sufferers on odevixibat in comparison with placebo. According to the enhancements noticed in pruritus, therapy with odevixibat led to vital enhancements in a number of observer-reported consequence sleep parameters. The general incidence of therapy emergent antagonistic occasions with odevixibat was much like placebo, with a low drug-related diarrhea price in sufferers with ALGS. All sufferers accomplished the research and 50 out of 52 sufferers have joined the extension research with all receiving odevixibat.²

Article content material

ENDS

About PBC
PBC is a uncommon, autoimmune, cholestatic liver illness, affecting roughly 9 ladies for each one man. A build-up of bile and toxins (cholestasis) and power irritation causes fibrosis (scarring) of the liver and destruction of the bile ducts. It’s a life-long situation that may worsen over time if not successfully handled, resulting in liver transplant and in some circumstances, untimely loss of life. PBC impacts sufferers’ every day lives by means of debilitating signs together with mostly pruritus and fatigue. At present, there are not any authorised remedies obtainable that may successfully handle each illness development and life-impacting signs.

About Iqirvo^® (elafibranor)
Iqirvo® (pronounced EYE-KER-VO) is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR) agonist, which exerts an impact on PPARα and PPARδ, that are regarded as key regulators of bile acid (BA) homeostasis, irritation and fibrosis. Pharmacological exercise that’s probably related to Iqirvo therapeutic results contains inhibition of bile acid synthesis by means of activation of PPARα and PPARδ. The proposed indication is for the therapy of main biliary cholangitis (PBC) together with ursodeoxycholic acid (UDCA) in adults who’ve an insufficient response to UDCA, or as monotherapy in sufferers unable to tolerate UDCA. In 2019, Iqirvo was granted Breakthrough Remedy Designation by the usFood and Drug Administration (FDA) in adults with PBC who’ve an insufficient response to ursodeoxycholic acid (UDCA). UCDA being the prevailing first-line remedy for PBC. Iqirvo has not acquired approval by regulatory authorities outdoors of the U.S. Iqirvo is at present underneath regulatory assessment awaiting a remaining resolution from the European Fee. It’s also in regulatory processes with different authorities together with the UK Medicines and Healthcare merchandise Regulatory Company (MHRA). Iqirvo (elafibranor) was found and developed by Genfit and Ipsen licensed the unique worldwide rights (besides China, Hong Kong, Taiwan and Macau) to elafibranor from Genfit in 2021.

Article content material

About ELATIVE
ELATIVE¹ is a multi-center, randomized, double-blind, placebo-controlled Part III medical trial, with an open-label long-term extension (NCT04526665). ELATIVE evaluated the efficacy and security of elafibranor 80mg as soon as every day versus placebo for the therapy of sufferers with PBC with an insufficient response or intolerance to ursodeoxycholic acid (UDCA), the prevailing first-line remedy for PBC. The trial enrolled 161 sufferers who had been randomized 2:1 to obtain elafibranor 80mg as soon as every day or placebo. Sufferers with an insufficient response to UDCA would proceed to obtain UDCA together with elafibranor or placebo, whereas sufferers unable to tolerate UDCA would obtain solely elafibranor or placebo. Sufferers continued their assigned therapy after Week 52 till all sufferers had accomplished their therapy or for a most of 104 weeks. Knowledge was additionally collected throughout this era, and extra analyses had been carried out with a deal with Week 78.

Within the trial, outcomes present statistically vital enhancements within the main composite endpoint of biochemical response, outlined as alkaline phosphatase (ALP) &LT1.67 x higher restrict of regular (ULN), an ALP lower ≥ 15 % and complete bilirubin (TB) ≤ ULN at 52 weeks, with a big therapy profit demonstrating a 47% placebo-adjusted distinction (P&LT0.001) between sufferers on elafibranor 80mg (51%) in contrast with sufferers on placebo (4%) reaching a biochemical response. ALP and bilirubin are vital predictors of PBC illness development. Reductions in ranges of each can point out lowered cholestatic harm and improved liver perform.

Article content material

Solely sufferers receiving elafibranor achieved normalization of ALP (higher restrict of regular 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 numerous biochemical impact of elafibranor measured by ALP discount was additional supported by knowledge demonstrating reductions from baseline in ALP ranges had been speedy, seen as early as Week 4 within the elafibranor group, and had been sustained by means of Week 52, with a lower in ALP of 41% on elafibranor in contrast with placebo.

Elafibranor was nicely tolerated within the trial. Comparable percentages of sufferers within the therapy group and the placebo group skilled antagonistic occasions, treatment-related antagonistic occasions, extreme or severe antagonistic occasions or antagonistic occasions resulting in discontinuation. Opposed occasions occurring in >10% of sufferers and extra continuously on elafibranor versus placebo included stomach ache, diarrhea, nausea, and vomiting.

About ALGS
ALGS is an inherited uncommon, genetic dysfunction that may have an effect on a number of organs together with the liver, coronary heart, skeleton, eyes and kidneys. Liver injury could consequence from having fewer than regular, narrowed or malformed bile ducts, which ends up in a build-up of poisonous bile acid, often called cholestasis and this in flip could cause fibrosis and progressive liver illness. Roughly 95% of sufferers with the situation current with power cholestasis, normally throughout the first three months of life and as many as 88% additionally current with extreme, intractable pruritus or itch. The estimated international incidence of ALGS is 3 in 100,000 stay births.

Article content material

About Kayfanda^® (odevixibat)
Kaydanda^® (odevixibat) is a once-daily non-systemic ileal bile acid transport (IBAT) inhibitor being investigated within the E.U. for the therapy of cholestatic pruritus in Alagille syndrome (ALGS) in sufferers aged 6 months or older. Odevixibat was authorised in June 2021 within the E.U. underneath the model identify Bylvay ^®, as the primary drug therapy possibility for all sorts of progressive familial intrahepatic cholestasis (PFIC) in sufferers aged 6 months or older, and within the U.S. underneath the model identify Bylvay®, as the primary drug therapy possibility for sufferers 3 months of age and older dwelling with cholestatic pruritus resulting from PFIC. Bylvay has acquired orphan exclusivity for the therapy of PFIC within the E.U. and within the U.S. In June 2023 Bylvay was authorised within the U.S. for the therapy of cholestatic pruritus in sufferers from 12 months of age with ALGS and acquired orphan exclusivity for ALGS. In October 2023, whereas the EMA’s CHMP beneficial the approval of Bylvay in ALGS, the EMA’s Committee for Orphan Medicinal Merchandise (COMP) beneficial to not preserve orphan exclusivity within the E.U. for Bylvay in ALGS. As a way to guarantee sustainable entry and availability for Bylvay within the authorised indication for the therapy of PFIC, which is supported by orphan drug standing, odevixibat for the therapy of ALGS has been resubmitted to the EMA underneath a brand new model identify, Kayfanda, with out orphan designation and is at present awaiting a remaining resolution from the European Fee.  

Article content material

About ASSERT
ASSERT² is a double-blind, randomized, placebo-controlled trial designed to judge the security and efficacy of 120 µg/kg/day Bylvay (odevixibat) for twenty-four weeks in relieving pruritus in sufferers with ALGS carried out in 52 sufferers with 32 websites throughout North America, Europe, Center East, and Asia Pacific.

The trial enrolled sufferers aged 0 to 17 years of age with a genetically confirmed prognosis of ALGS. Within the main evaluation, the research met the first endpoint exhibiting extremely statistically vital enchancment in pruritus for sufferers on odevixibat as measured by the PRUCISION Observer-Reported Consequence scratching rating (0-4 level scale), from baseline at month 6 (weeks 21 to 24), in comparison with the placebo arm (p=0.002). Greater than 90% of sufferers had been pruritus responders (≥ 1 level change at any time throughout 24 weeks).

The research additionally met the important thing secondary endpoint exhibiting a extremely statistically vital discount in serum bile acid focus from baseline to the typical of weeks 20 and 24 (in comparison with the placebo arm p=0.001). Statistically vital enhancements in a number of sleep parameters had been noticed as early as weeks 1-4 in comparison with sufferers on placebo with continued enchancment by means of week 24.

Article content material

Within the research, there have been no affected person discontinuations and 96% of sufferers rolled over into the open-label extension research. Bylvay had an general antagonistic occasion incidence much like placebo and a low incidence of drug-related diarrhea (11.4% vs. 5.9% placebo).

The detailed suggestions for the usage of odevixibat are described within the Abstract of Product Traits (EU SmPC) and U.S. Prescribing Info (USPI)

About Ipsen

We’re a worldwide biopharmaceutical firm with a deal with bringing transformative medicines to sufferers in three therapeutic areas: Oncology, Uncommon Illness and Neuroscience.

Our pipeline is fuelled by exterior innovation and supported by practically 100 years of improvement expertise and international hubs within the U.S., France and the U.Ok. Our groups in additional than 40 nations and our partnerships around the globe allow us to carry medicines to sufferers in additional than 80 nations.

Ipsen is listed in Paris (Euronext: IPN) and within the U.S. by means of a Sponsored Stage I American Depositary Receipt program (ADR: IPSEY). For extra data, go to ipsen.com.

Article content material

Ipsen contacts

Buyers

• 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 Ahead-Trying Statements

The forward-looking statements, goals and targets contained herein are based mostly on Ipsen’s administration technique, present views and assumptions. Such statements contain identified and unknown dangers and uncertainties which will trigger precise outcomes, efficiency or occasions to vary materially from these anticipated herein. All the above dangers may have an effect on Ipsen’s future capability to attain its monetary targets, which had been set assuming affordable macroeconomic situations based mostly on the data obtainable at this time. Use of the phrases ‘believes’, ‘anticipates’ and ‘expects’ and comparable expressions are meant to establish forward-looking statements, together with Ipsen’s expectations relating to future occasions, together with regulatory filings and determinations. Furthermore, the targets described on this doc had been ready with out bearing in mind external-growth assumptions and potential future acquisitions, which can alter these parameters. These goals are based mostly on knowledge and assumptions considered affordable by Ipsen. These targets depend upon situations or information more likely to occur sooner or later, and never completely on historic knowledge. Precise outcomes could depart considerably from these targets given the incidence of sure dangers and uncertainties, notably the truth that a promising drugs in early improvement section or medical trial could find yourself by no means being launched available on the market or reaching its business targets, notably for regulatory or competitors causes. Ipsen should face or would possibly face competitors from generic drugs which may translate right into a lack of market share. Moreover, the analysis and improvement course of entails a number of levels every of which entails the substantial threat that Ipsen could fail to attain its goals and be compelled to desert its efforts as regards to a drugs through which it has invested vital sums. Subsequently, Ipsen can’t be sure that favorable outcomes obtained throughout preclinical trials can be confirmed subsequently throughout medical trials, or that the outcomes of medical trials can be ample to display the secure and efficient nature of the medication involved. There might be no ensures a drugs will obtain the mandatory regulatory approvals or that the medication will show to be commercially profitable. If underlying assumptions show inaccurate or dangers or uncertainties materialize, precise outcomes could differ materially from these set forth within the forward-looking statements. Different dangers and uncertainties embody however will not be restricted to, normal business situations and competitors; normal financial components, together with rate of interest and foreign money alternate price fluctuations; the influence of pharmaceutical business regulation and healthcare laws; international traits towards healthcare price containment; technological advances, new drugs and patents attained by rivals; challenges inherent in new-medicine improvement, together with acquiring regulatory approval; Ipsen’s capability to precisely predict future market situations; manufacturing difficulties or delays; monetary instability of worldwide economies and sovereign threat; dependence on the effectiveness of Ipsen’s patents and different protections for revolutionary medicines; and the publicity to litigation, together with patent litigation, and/or regulatory actions. Ipsen additionally is determined by third events to develop and market a few of its medicines which may probably generate substantial royalties; these companions may behave in such methods which may trigger injury to Ipsen’s actions and monetary outcomes. Ipsen can’t be sure that its companions will fulfil their obligations. It could be unable to acquire any profit from these agreements. A default by any of Ipsen’s companions may generate decrease revenues than anticipated. Such conditions may have a unfavourable influence on Ipsen’s enterprise, monetary place or efficiency. Ipsen expressly disclaims any obligation or enterprise to replace or revise any forward-looking statements, targets or estimates contained on this press launch to replicate any change in occasions, situations, assumptions or circumstances on which any such statements are based mostly, except so required by relevant regulation. Ipsen’s enterprise is topic to the chance components outlined in its registration paperwork filed with the French Autorité des Marchés Financiers. The dangers and uncertainties set out will not be exhaustive and the reader is suggested to consult with Ipsen’s newest Common Registration Doc, obtainable on ipsen.com.

References

1. Kowdley. Ok.V, et al. Efficacy and Security of Elafibranor in Major Biliary Cholangitis. NEJM. 2023. DOI: 10.1056/NEJMoa2306185
2. Ovchinsky N., et al. Efficacy and security of odevixibat in sufferers with Alagille syndrome (ASSRT); a section 3, double-blind, randomized, placebo-controlled trial. Lancet Gastroenterol / Hepatol. 2024 doi.org/10.1016/S2468-1253(24)00074-8

Attachment

• PR_CHMP_Iqirvo and Kayfanda_260724

Article content material