RegulationOrphan Drug (US), Overseas New Drugs Urgently Needed in Clinical Settings (CN), Priority Review (CN), Special Review Project (CN), Orphan Drug (JP)

Structure

Molecular FormulaC27H31N5O7S

InChIKeySXTRWVVIEPWAKM-UHFFFAOYSA-N

CAS Registry157212-55-0

186

Clinical Trials associated with Bosentan

CTR20243649 / RecruitingNot Applicable

波生坦分散片人体生物等效性研究

[Translation] Study on the bioequivalence of bosentan dispersible tablets in healthy volunteers

本试验旨在研究单次空腹和餐后口服江苏天士力帝益药业有限公司研制、生产的波生坦分散片（32 mg（以C27H29N5O6S计））的药代动力学特征；以Actelion Pharmaceuticals Ltd持证、Patheon Inc.生产的波生坦分散片（Tracleer®，32 mg（以C27H29N5O6S计））为参比制剂，比较两制剂中药动学参数Cmax、AUC0-t、AUC0-∞，评价两制剂的人体生物等效性。

[Translation]

This study aimed to investigate the pharmacokinetic characteristics of bosentan dispersible tablets (32 mg (calculated as C27H29N5O6S)) developed and produced by Jiangsu Tasly Diyi Pharmaceutical Co., Ltd. after single oral administration on an empty stomach or after a meal; using bosentan dispersible tablets (Tracleer®, 32 mg (calculated as C27H29N5O6S)) licensed by Actelion Pharmaceuticals Ltd and produced by Patheon Inc. as the reference preparation, to compare the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ of the two preparations, and to evaluate the bioequivalence of the two preparations in humans.

Start Date18 Sep 2024

Sponsor / Collaborator

Jiangsu Tasly Diyi Pharmaceutical Co., Ltd.

NCT06058585 / RecruitingPhase 3IIT

The Chronic Kidney Disease Adaptive Platform Trial Investigating Various Agents for Therapeutic Effect

CAPTIVATE is an international, multi-centre, Phase III, adaptive, platform, randomised controlled trial in people with chronic kidney disease (CKD).
CAPTIVATE aims to find the best treatment, or combination of treatments, that slow the progression of CKD so that fewer people develop kidney failure.
CAPTIVATE provides a research platform that allows many treatment-related questions to be answered within a common trial set-up.

Start Date19 Aug 2024

Sponsor / Collaborator-

NCT06432452 / Not yet recruitingPhase 2/3IIT

Efficacy of Endothelin Receptor Antagonism in Treatment of Coronary Artery Spasm: a Randomized Controlled Clinical Trial

The goal of this randomized clinical trial is to assess if adjunctive bosentan therapy, in comparison to placebo, can reduce the rate of epicardial vasospasm at follow-up spasm provocation CFT (fuCFT) in patients with previously proven epicardial vasospasm on acetylcholine reactivity testing (at index CFT) and ongoing angina(-like) complaints.
Participants will
Use either endothelin receptor antagonist or placebo for 10 weeks
Undergo follow-up acetylcholine spasm provocation test after 10 weeks
Answer online questionnaires on angina and quality of life

Start Date01 Aug 2024

Sponsor / Collaborator

Radboud University Medical Center

[+2]

100 Clinical Results associated with Bosentan

100 Translational Medicine associated with Bosentan

100 Patents (Medical) associated with Bosentan

2,466

Literatures (Medical) associated with Bosentan

31 Dec 2024·Journal of medical economics

Comparative adherence of macitentan versus ambrisentan and bosentan in Australian patients with pulmonary arterial hypertension: a retrospective real-world database study

Article

Author: Tan, Jin Yu ; Casorso, Jeremy ; Bloomfield, Paul ; Lau, Edmund ; Kouhkamari, Mahsa H ; Lim, Sooyeol ; Yu, Dae Young ; Wu, David Bin-Chia ; Kotlyar, Eugene ; Makanji, Yogeshwar

AIM:

Bosentan, ambrisentan, and macitentan are endothelin receptor antagonists (ERAs), currently available in Australia for treatment of pulmonary arterial hypertension (PAH). This study assessed the comparative adherence of these ERAs for PAH in Australian patients.

METHODS:

This retrospective, observational study used data for adults with PAH from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset (01/2006-10/2020). The primary outcome was treatment adherence (i.e. receiving ≥80% of ERA doses over 12 months). Secondary outcomes were time to treatment change (add-on or switch) and overall survival.

RESULTS:

The study included 436 patients who took bosentan (n = 200), ambrisentan (n = 69), or macitentan (n = 167). Treatment adherence was significantly greater in patients who received macitentan (65.3%) versus ambrisentan (56.5%) and bosentan (58.0%), with odds ratios (ORs; 95% CI) of 0.51 (0.30-0.88; p = 0.016) for bosentan versus macitentan and 0.48 (0.24-0.96; p = 0.037) for ambrisentan versus macitentan. The median time to treatment change was 47.2 and 43.4 months for bosentan and ambrisentan, respectively (not calculated for macitentan because of insufficient duration of data).

LIMITATIONS AND CONCLUSIONS:

Real-world data for Australian patients with PAH showed that treatment adherence for ERAs was suboptimal. Adherence was higher for macitentan compared with ambrisentan and bosentan.

01 Oct 2024·ESC Heart Failure

Pulmonary artery denervation versus conventional therapies for PAH: a systematic review and updated network meta‐analysis

Review

Author: Wei, Yongyue ; Chen, Feng ; Pan, Zoucheng ; Chen, Shao‐liang ; Kan, Jing ; Zhang, Longyao ; Wang, Xiang ; Wu, Xiaoyu

Abstract:

Aims:

A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta‐analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies.

Methods and results:

According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta‐analyses. Data were extracted and curated for Bayesian network meta‐analysis. The primary outcome was the change in the 6‐min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (−77.76 m, 95% CI: −102.04 to −54.34 m), Macitentan (−65.32 m, 95% CI: −95.34 to −36.1 m), Bosentan (−64.5 m, 95% CI: −94.7 to −35.07 m), Iloprost (−62.66 m, 95% CI: −99.48 to −27.13 m), Oxygen (−62.42 m, 95% CI: −100.01 to −25.78 m), Treprostinil (−62.01 m, 95% CI: −89.04 to −35.61 m), Riociguat (−60.59 m, 95% CI: −86.11 to −35.98 m), Selexipag (−47.2 m, 95% CI: −85.61 to −10.19 m), Sildenafil (−44.92 m, 95% CI: −74.43 to −16.15 m), or Sitaxsentan (−39.53 m, 95% CI: −78.99 to −0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re‐hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions.

Conclusions:

Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual‐drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

01 Oct 2024·Biochemical pharmacology

Role of endothelin ETA receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats

Article

Author: Pannucci, Patrizia ; Van Daele, Marieke ; March, Julie ; Wragg, Edward S ; Woolard, Jeanette ; Hill, Stephen J ; Groenen, Marleen ; Cooper, Samantha L

Receptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatinib, are associated with hypertensive side effects. Doppler flowmetry was used to evaluate regional haemodynamic profiles of axitinib and lenvatinib. Male Sprague Dawley rats (350-500 g) were instrumented with Doppler flow probes (renal and mesenteric arteries and descending abdominal aorta) and catheters (jugular vein and distal abdominal aorta, via the caudal artery). Rats were dosed daily with axitinib (3 or 6 mg.kg^-1) or lenvatinib (1 or 3 mg.kg^-1) and regional haemodynamics were recorded over a maximum of 4 days. Both RTKIs caused significant (p < 0.05) increases in mean arterial pressure (MAP), which was accompanied by significant (p < 0.05) vasoconstriction in both the mesenteric and hindquarters vascular beds. To gain insight into the involvement of endothelin-1 (ET-1) in RTKI-mediated hypertension, we also monitored heart rate (HR) and MAP in response to axitinib or lenvatinib in animals treated with the ET_A receptor selective antagonist sitaxentan (5 mg.kg^-1) or the mixed ET_A/ET_B receptor antagonist bosentan (15 mg.kg^-1) over two days. Co-treatment with bosentan or sitaxentan markedly reduced the MAP effects mediated by both RTKIs (p < 0.05). Bosentan, but not sitaxentan, also attenuated ET-1 mediated increases in HR. These data suggest that selective antagonists of ET_A receptors may be appropriate to alleviate the hypertensive effects of axitinib and lenvatinib.

News (Medical) associated with Bosentan

29 Oct 2024

·www.globenewswire.com

Idorsia announces financial results for the first nine months of 2024

Ad hoc announcement pursuant to Art. 53 LR Allschwil, Switzerland – October 29, 2024 Idorsia Ltd (SIX: IDIA) today announced its financial results for the first nine months of 2024. Highlights Net revenue 9M 2024 at CHF 53 million.US GAAP operating loss 9M 2024 of CHF 154 million and Non-GAAP operating loss of CHF 248 million.Improved Guidance for 2024, driven by diligent cost control.QUVIVIQ™ (daridorexant) total net sales of CHF 39 million in 9M 2024.Commercial partnership for QUVIVIQ with Menarini France.QUVIVIQ approved for the treatment of insomnia in Japan.TRYVIO™ (aprocitentan) commercially available in the US since October 2024.JERAYGO™ (aprocitentan) approved by the European Commission in June 2024 and marketing authorization applications submitted in the UK, Canada, and Switzerland.Collaboration with Neurocrine Biosciences comes to an end. André C. Muller, Chief Executive Officer of Idorsia, commented:“The one thing everyone wants to hear about – both internally and externally – is the status of a deal with aprocitentan. I’m pleased to share that our efforts on this front are advancing well. Our improved financial guidance includes our cost-conscious attitude across the whole organization, without compromising advancements, such as making progress in ramping up sales of QUVIVIQ, making TRYVIO available in the US, and expanding marketing authorization for JERAYGO.” Financial results US GAAP resultsNine MonthsThird Quarterin CHF millions, except EPS (CHF) and number of shares (millions)2024202320242023Net revenues531312680Operating expenses(211)(275)(118)150Operating income (loss)(154)(144)(90)231Net income (loss)(180)(181)(101)224Basic EPS(1.00)(1.02)(0.55)1.26Basic weighted average number of shares180.5178.2182.4178.4Diluted EPS(1.00)(1.02)(0.55)0.96Diluted weighted average number of shares180.5178.2182.4232.5 Net revenue of CHF 53 million in the first nine months of 2024 is the result of QUVIVIQ product sales (CHF 39 million), product sales to partners in the Asia-Pacific-Region (CHF 9 million) and contract revenue recognized in connection with Owkin (CHF 3 million). This compares to CHF 131 million in the first nine months of 2023, which included CHF 34 million sales of PIVLAZ in Japan (assigned in the meantime to Nxera Pharma as part of a transaction, more details can be found in the dedicated press release) and CHF 68 million one-off impact of the Nxera deal as well as CHF 4 million revenue share from Johnson & Johnson related to ponesimod sales (revenue-sharing agreement now eliminated as part of the reacquisition of aprocitentan, more details can be found in the dedicated press release). US GAAP operating expenses in the first nine months of 2024 benefited from extraordinary income of CHF 125 million from the Viatris deal resulting in an expense of CHF 211 million (CHF 275 million in the first nine months of 2023), of which CHF 16 million related to cost of sales (CHF 7 million in the first nine months of 2023), CHF 111 million to R&D expenses (CHF 235 million in the first nine months of 2023), and CHF 209 million to SG&A expenses (CHF 318 million in the first nine months of 2023). US GAAP net loss in the first nine months of 2024 amounted to CHF 180 million (CHF 181 million net loss in the first nine months of 2023). The net loss was favorably impacted by a one-off income related to the Viatris deal of CHF 125 million (CHF 302 million one-off income related to the Nxera deal in the first nine months of 2023) and lower operating expenses throughout all functions. The US GAAP net loss resulted in a basic net loss per share of CHF 1.00 (basic and diluted) in the first nine months of 2024, compared to a net loss per share of CHF 1.02 (basic and diluted) in the first nine months of 2023. Non-GAAP* measuresNine MonthsThird Quarterin CHF millions, except EPS (CHF) and number of shares (millions)2024202320242023Net revenues531312680Operating expenses(305)(517)(106)(124)Operating income (loss)(248)(386)(78)(44)Net income (loss)(258)(420)(75)(51)Basic EPS(1.43)(2.36)(0.41)(0.29)Basic weighted average number of shares180.5178.2182.4178.4Diluted EPS(1.43)(2.36)(0.41)(0.29)Diluted weighted average number of shares180.5178.2182.4178.4 * Idorsia measures, reports, and issues guidance on non-GAAP operating performance. Idorsia believes that these non-GAAP financial measurements more accurately reflect the underlying business performance and therefore provide useful supplementary information to investors. These non-GAAP measures are reported in addition to, not as a substitute for, US GAAP financial performance. Non-GAAP net loss in the first nine months of 2024 amounted to CHF 258 million: the CHF 78 million difference versus US GAAP net loss was mainly due to the one-off effect of the Viatris deal (CHF 125 million income), depreciation and amortization (CHF 14 million), share-based compensation (CHF 17 million) and a consent fee paid in shares to the bondholders resulting from amended terms of the 2024 convertible bonds (CHF 14 million). The non-GAAP net loss resulted in a net loss per share of CHF 1.43 (basic and diluted) in the first nine months of 2024, compared to a net loss per share of CHF 2.36 (basic and diluted) in the first nine months of 2023. Viatris collaborationIn March 2024, Idorsia closed agreements with Viatris Inc. (NASDAQ: VTRS), a global healthcare company, for collaboration on the global development and commercialization of two Phase 3 assets – selatogrel and cenerimod – with Idorsia receiving an upfront payment of USD 350 million, and the right to potential development and regulatory milestone payments of up to USD 300 million, potential sales milestone payments of up to USD 2.1 billion, and potential contingent tiered royalties from mid-single- to low-double-digit percentage on annual net sales. A joint development committee is overseeing the development of the ongoing Phase 3 programs for selatogrel and cenerimod up to regulatory approval. Idorsia will contribute up to USD 200 million in the next 3 years and transferred the dedicated personnel for both programs to Viatris. Viatris has worldwide commercialization rights for both selatogrel and cenerimod (excluding, for cenerimod only, Japan, South Korea, and certain countries in the Asia-Pacific region). Idorsia has also granted Viatris a right of first refusal and first negotiation for certain other pipeline assets. Convertible bonds 2024In July 2018, the Group issued CHF 200 million of senior unsecured convertible bonds (ISIN: CH0426820350), which were due to mature on July 17, 2024. On May 6, 2024, a bondholder meeting was held, where 83.5% of the total outstanding bondholders voted in favor of amendments to the terms of the bonds. The approved bond terms include an amended conversion price of CHF 6.00, extended maturity date of January 17, 2025, and the option to call the bonds at par, in full or in part, at any time upon giving ten trading days' notice. A consent fee of 8,000 shares per Bond was paid to bondholders on September 5, 2024. Financial outlook 2024For 2024 – excluding unforeseen events – the company expects QUVIVIQ net sales of around CHF 55 million; SG&A expenses of around CHF 265 million; R&D expense of around CHF 130 million for Idorsia-led pipeline assets; non-GAAP operating expenses around CHF 400 million. This performance would result in a non-GAAP operating loss of around CHF 350 million (excluding contract revenues and the one-off benefit from the Viatris deal). The company expects US GAAP operating loss for 2024 to reach CHF 260 million which includes a one-off benefit of CHF 125 million from the Viatris deal. Arno Groenewoud, Chief Financial Officer, commented:“While closing a deal for TRYVIO is a key focal point, we have also sharpened our cost-conscious approach, which we will increase going forward. Hence, we have been able to stretch the cash runway out to about year-end 2024, which allows us to appropriately plan and execute the next steps of our financial strategy. Furthermore, as a result of lower than expected spending we can upgrade our US GAAP and non-GAAP operating loss guidance by around 60 million Swiss francs each, taking them to 260 million and 350 million Swiss francs, respectively.” Liquidity and indebtednessAt the end of the first nine months of 2024, Idorsia’s liquidity amounted to CHF 92 million. (in CHF millions)Sep 30, 2024Jun 30, 2024Dec 31, 2023Liquidity Cash and cash equivalents92237145Total liquidity*92237145 Indebtedness Convertible loan335335335Convertible bond797797796Other financial debt162162162Total indebtedness1,2941,2941,293 *rounding differences may occur Commercial operationsIn the first nine months of 2024, QUVIVIQ™ (daridorexant) in the US, Germany, Italy, Switzerland, Spain, UK, Canada, Austria, and France generated total product sales of CHF 39 million. United States ProductMechanism of actionIndicationCommercially available sinceDual orexin receptor antagonistTreatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenanceMay 2022 In the US, net sales of QUVIVIQ® (daridorexant) in the first nine months of 2024 reached CHF 21 million, an increase of +41% versus the first nine months of 2023. As of the end of the third quarter 2024, more than 165,000 patients have been treated with QUVIVIQ since launch in the US, over 500,000 prescriptions have been dispensed, and the product has been prescribed by almost 50,000 healthcare professionals. Tosh Butt, President, and General Manager of Idorsia US, commented:“Due to budget constraints we have recently reduced our field force for QUVIVIQ. Despite the reduction, the sales are holding-up for now. Importantly, the citizen petition requesting a review of the evidence from available data, which will hopefully lead to the descheduling of the DORA class of chronic insomnia medications, continues to make progress.” For more information about QUVIVIQ in the US, see the Full Prescribing Information (PI and Medication Guide). ProductMechanism of actionIndicationCommercially available sinceDual endothelin receptor antagonistTreatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugsOctober 2024 On March 19, 2024, the US Food and Drug Administration (FDA) approved TRYVIO™ (aprocitentan) for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food. Tosh Butt concluded:“Idorsia is making robust progress with the preparation of everything required for a full commercial launch of TRYVIO by the end of the first quarter of 2025. Both the REMS program and specialty distribution channel are fully up and running, we have begun engaging with hypertension experts through our presence at major cardiovascular and nephrology congresses. The initial discussions with payors are also encouraging. TRYVIO is now available to prescribe to the millions of patients in the US whose high blood pressure is not adequately controlled by other drugs. We have everything in place except a field-force and funding for promotional activities, which is dependent on a partnership deal.” Further details on the approval, together with commentary from company management can be found in the dedicated press release and investor webcast available from the company corporate website. For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). Europe and Canada ProductMechanism of actionIndicationCommercially availableDual orexin receptor antagonistTreatment of adult patients with insomnia characterised by symptoms present for at least three months and considerable impact on daytime functioningSweden: Sept. 2024France: Mar. 2024Austria: Feb. 2024UK: Oct. 2023Spain: Sept. 2023Switzerland: Jun. 2023Germany: Nov. 2022Italy: Nov. 2022 Management of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenanceCanada: Nov. 2023 QUVIVIQ (daridorexant) net sales in the first nine months of 2024 reached CHF 18 million in the EUCAN region. In the third quarter of 2024, net sales have increased by 46% compared to the second quarter of 2024. In Germany, QUVIVIQ was launched in November 2022. By law, sleep medications were then subject to a 4-week prescribing limitation (Anlage III BtMG). Following a review by the Federal Joint Committee (G-BA) this limitation was lifted for QUVIVIQ in November 2023. This makes it the only sleep medication in Germany that can be prescribed for long-term treatment of chronic insomnia. In December 2023, the price negotiated for QUVIVIQ under the AMNOG process became effective. Following the lifting of the prescribing limitation, the company submitted a second AMNOG dossier for the long-term treatment of chronic insomnia disorder (beyond 4 weeks), reflecting the indication approved by the EMA in 2022. The second AMNOG process is expected to end in March 2025. The progress made in Germany is reflected by the performance of QUVIVIQ on the market, with sales doubling in the first nine months of 2024 compared to the first nine months of 2023. In Italy, QUVIVIQ was launched in November 2022. Currently, QUVIVIQ can only be prescribed by neurologists, psychiatrists, and specialists from sleep centers, and no sleep therapy is reimbursed. The company submitted a reimbursement dossier in June 2023 and requested the expansion of the prescriber base. The submission – detailing the efficacy and safety profile of QUVIVIQ and its estimated budget impact and cost-effectiveness in Italy – is under review, with a hearing expected to take place before the end of the year. In Switzerland, QUVIVIQ was launched to the self-pay market in June 2023. Following the launch of QUVIVIQ, awareness and sales have increased solidly. Reimbursement discussions are ongoing and remain a priority for Switzerland. In Spain, QUVIVIQ was launched to the self-pay market in September 2023. Spain represents the largest insomnia market in Europe, as was apparent in the first months of this product’s availability, despite it only being launched to the self-pay market. The company submitted a reimbursement dossier to the Spanish authorities in July 2024, in order to allow equal access for all patients with chronic insomnia. In the UK, QUVIVIQ is recommended as first-line pharmaceutical treatment for patients with chronic insomnia, after, or as an alternative to, cognitive behavioral therapy for insomnia (CBT-I). QUVIVIQ was launched in October 2023 and the team has achieved full reimbursement throughout the UK. The priority in the UK is to secure regional access, which currently stands at around 80%, as well as raising awareness of QUVIVIQ among general practitioners. In Austria, QUVIVIQ was made available in February 2024. A reimbursement dossier was submitted in October 2024, with a conclusion expected in the second half of 2025. In France, QUVIVIQ was included in both the hospital and the retail formulary list of reimbursed pharmaceutical specialties in January 2024 and launched in March 2024 as the first and only pharmacotherapy recommended for the treatment of chronic insomnia disorder. There was a very strong uptake at launch largely due to the excellent market preparation work with psychiatrists. This can be seen by the fact that the majority of prescriptions are being made by the specialists, despite the French market being composed of 55’000 general practitioners who between them represent 75% of the insomnia prescriptions. As a result, the priority becomes expanding awareness to the primary care market to secure strong long-term growth. To address this, Idorsia is expanding its commercial reach from specialist prescribers to general practitioners (GPs) through a new commercial partnership with Menarini in France. In Sweden, QUVIVIQ was made available in September 2024. A reimbursement dossier was submitted in May 2024. As a result, a decision on reimbursement is expected by the end of 2024. In Canada, after being approved in April 2023, QUVIVIQ was launched in November 2023 to the private market, representing 55% of the Canadian insomnia market. The reimbursement dossier was submitted to private market payers in the third quarter of 2023 and currently stands at 80% coverage. The focus is now on public payers with the submission confirmation in Quebec received in October 2024 and submissions in all other provinces ongoing and to be completed by year end. Benjamin Limal, President of Europe and Canada region, commented:“Securing public access to Europe’s only dual orexin receptor antagonist remains our number one priority throughout the EUCAN region – this is the pathway to unlocking the true value of QUVIVIQ. Until then, the performance is satisfactory with a great adoption from specialists and a strong quarterly growth in demand and sales. As one of the newest launches, I have to mention France – QUVIVIQ is really off to a flying start and we are quickly reinforcing the launch momentum through a commercial partnership with Menarini, experts with established relationships in primary care, to handle the promotion of QUVIVIQ to GPs.” For more information about QUVIVIQ in the EU, see the Summary of Product Characteristics. For more information about QUVIVIQ in Switzerland, see the Patient Information and Information for Healthcare Professionals. For more information on the marketing authorization of QUVIVIQ in Canada, see the Product Monograph. ProductMechanism of actionIndicationCommercially available sinceDual endothelin receptor antagonistTreatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal productsApproved Jun. 2024 On June 27, 2024, the European Commission (EC) approved JERAYGO™ (aprocitentan) for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. The recommended dose is 12.5 mg orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure (BP) control. Further details on the approval, together with commentary from company management can be found in the dedicated press release available from the company corporate website. For more information about JERAYGO in the EU, see the Summary of Product Characteristics. Research & DevelopmentIdorsia has a diversified and balanced portfolio, comprising assets developed and/or marketed by Idorsia and assets that are partner-led to maximize the value we have created. Our drug discovery engine has produced innovative drugs with the potential to transform the treatment paradigm in multiple therapeutic areas, including CNS, cardiovascular, and immunological disorders, as well as orphan diseases. The company also has a vaccine platform for the discovery and development of glycoconjugate vaccines containing synthetic antigenic glycan molecules, with or without a carrier protein, to prevent infection. Idorsia-led portfolio CompoundMechanism of actionTarget indicationStatusQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaCommercially available in the US, Germany, Italy, Switzerland, Spain, the UK, Canada, Austria, France, and Sweden; approved throughout the EUTRYVIO™ (aprocitentan) Dual endothelin receptor antagonistSystemic hypertension in combination with other antihypertensivesCommercially available in the USJERAYGO™ (aprocitentan)Dual endothelin receptor antagonistResistant hypertension in combination with other antihypertensivesApproved in the EU; Marketing authorization applications submitted in the UK, Canada, and SwitzerlandLucerastatGlucosylceramide synthase inhibitorFabry diseasePhase 3 primary endpoint not met; open-label extension study ongoingPhase 3 focused on renal function in preparationDaridorexantDual orexin receptor antagonistPediatric insomniaPhase 2 in pediatric insomnia ongoingACT-1004-1239ACKR3/CXCR7 antagonistDemyelinating diseases including multiple sclerosis Phase 2 in preparationACT-777991CXCR3 antagonistVitiligoPhase 2 in preparationSinbaglustatGBA2/GCS inhibitorRare lysosomal storage disordersPhase 1 completeIDOR-1117-2520UndisclosedImmune-mediated disordersPhase 1 ongoingIDOR-1134-2831Synthetic glycan vaccineClostridium difficile infectionPhase 1 ongoing Further details including the current status of each project in our portfolio can be found in our innovation fact sheet. Idorsia partner-led portfolioFor Idorsia, sophisticated partnerships are a way of gaining strategic access to technologies or products and fully exploiting our discovery engine and clinical pipeline. We seek suitable external project partners to maximize the value of internal innovation. CompoundMechanism of actionTarget indicationPartner/statusQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaSimcere: Approved for the treatment of insomnia in Hong-KongQUVIVIQ™ (daridorexant)Dual orexin receptor antagonistInsomniaNxera Pharma: license to develop and commercialize for Asia-Pacific region (excluding China)Approved for the treatment of insomnia in JapanDaridorexantDual orexin receptor antagonistInsomniaSimcere: license to develop and commercialize for Greater China regionNDA submitted in Greater ChinaSelatogrelP2Y12 inhibitorAcute myocardial infarctionViatris: worldwide development and commercialization rightsPhase 3 “SOS-AMI” program ongoingCenerimodS1P1 receptor modulatorSystemic lupus erythematosusViatris: worldwide development and commercialization rights (excluding Japan, South Korea, and certain countries in the Asia-Pacific region)Phase 3 “OPUS” program ongoingDaridorexantDual orexin receptor antagonistPosttraumatic stress disorder (PTSD)US Department of Defense (DOD): Idorsia is supporting a clinical study sponsored by the US DOD to develop new therapies to treat PTSDACT-1002-4391EP2/EP4 receptor antagonistImmuno-oncologyOwkin: global license to develop and commercializePhase 1 in preparation On October 1, 2024, Nxera Pharma announced that it had entered a commercial partnership agreement with Shionogi & Co., Ltd regarding the distribution and sales for QUVIVIQ in Japan. At the same time, the previous commercialization agreement between Nxera and Mochida Pharmaceutical Co., Ltd. was terminated. After negotiation among Nxera, Shionogi and Mochida regarding the optimal sales scheme, Shionogi is solely responsible for distribution and sales activities in Japan. Idorsia and Neurocrine Biosciences had a collaboration for ACT-709478, Idorsia’s novel T-type calcium channel blocker. The compound was investigated as a treatment of pediatric patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSCW), a rare form of pediatric epilepsy. The Phase 2 study did not meet the primary endpoint in June 2022, and further analysis from an open-label extension study resulted in the decision to stop further development. As a result, the development agreement has come to an end. Further details including the current status of each project in our partner-led portfolio can be found in our innovation fact sheet. Results Day CenterInvestor community: To make your job easier, we provide all relevant documentation via the Results Day Center on our corporate website: www.idorsia.com/results-day-center. Upcoming Financial Updates Full Year 2024 Financial Reporting together with the publication of the Annual Report 2024 on February 27, 2025 Notes to the editor About IdorsiaIdorsia Ltd is reaching out for more – We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development, and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 25-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America – the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 750 highly qualified specialists dedicated to realizing our ambitious targets. For further information, please contactAndrew C. WeissSenior Vice President, Head of Investor Relations & Corporate CommunicationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com media.relations@idorsia.com www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF

Drug ApprovalFinancial Statement

16 Oct 2024

·www.globenewswire.com

New data on aprocitentan to be presented at the ASN Kidney Week 2024

Allschwil, Switzerland – October 16, 2024 Idorsia Ltd (SIX: IDIA) today announced that new data on aprocitentan, Idorsia’s endothelin receptor antagonist, will be presented at the American Society of Nephrology (ASN) Kidney Week 2024, taking place in San Diego, CA, October 23–27, 2024. The following oral and poster presentations will be held, highlighting the promising results of using aprocitentan for patients with hypertension not adequately controlled with other medications, with positive effects on blood pressure and proteinuria measures, in patients with co-morbid chronic kidney disease (CKD) stage 3 and 4, and its favorable tolerability profile including the absence of aggravation of renal function and hyperkalemia. Bakris G. L., et al. “Aprocitentan in patients with chronic kidney disease (CKD): sub-group analysis of the PRECISION trial”, oral presentation by Markus Schlaich, abstract #: FR-OR48, session ‘Hypertension, CVD, and the Kidneys: Clinical Studies [OR1602], room 5 (Convention Center), Oct 25, 16:50 – 17:00.Bakris G. L., et al. “Incidence and prevalence of edema and the effect of aprocitentan treatment strategy in the PRECISION study”, poster presentation by Markus Schlaich, poster number SA-PO356, Exhibit Halls A-C, Oct 26, 10:00 – 12:00. Idorsia US will also be present at ASN Kidney Week with a TRYVIO (aprocitentan) commercial and medical information booth. Visit the team at booth #1705. In addition, data from the Phase 3 program with lucerastat, Idorsia’s glucosylceramide synthase inhibitor, will be presented as a poster: Wallace E. L., et al. “Lucerastat effect on kidney function in patients with Fabry Disease: Results from the Phase 3 clinical program”, poster presentation by Eric Wallace, poster number SA-PO654, Exhibit Halls A-C, Oct 26, 10:00 – 12:00. The abstracts will be published in the Journal of American Society of Nephrology and can be found in the ASN Kidney Week abstract supplement. Notes to the editor About aprocitentanAprocitentan is Idorsia’s once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of ET-1 to ETA and ETB receptors. In May 2022, Idorsia announced positive top-line results of the Phase 3 PRECISION study with aprocitentan for the treatment of patients with resistant hypertension. Detailed results were published in The Lancet and presented as a Late-Breaking Science presentation during the American Heart Association (AHA) Scientific Sessions in November 2022. More details and commentary can be found in the dedicated press release and an investor webcast featuring Prof. Markus Schlaich, an investigator in PRECISION. On March 19, 2024, aprocitentan was approved as TRYVIO™ in the US. On June 27, 2024, the European Commission granted market authorization for JERAYGO™ (aprocitentan). About lucerastatLucerastat is Idorsia’s oral inhibitor of glucosylceramide synthase, offering a potential new treatment approach for all patients living with Fabry disease, irrespective of the mutation type of the GLA gene. In October 2021, the company reported that lucerastat 1000 mg b.i.d. did not meet the primary endpoint of reducing neuropathic pain during 6 months of treatment versus placebo. However, Lucerastat demonstrated a substantial reduction in levels of the Fabry disease biomarker plasma Gb3 during the treatment period, with a decrease of approximately 50% observed in plasma Gb3 in the lucerastat treatment group compared to an increase of 12% in the placebo group. Furthermore, results suggested a treatment effect on kidney function. Lucerastat was well tolerated. Analysis of the ongoing open-label extension (OLE) of the Phase 3 study corroborated the long-term effect on plasma Gb3 levels and a potential positive long-term effect on kidney function. The analysis also showed a safety and tolerability profile consistent with that observed during the 6-month randomized treatment period. The company is conducting a kidney biopsy substudy within a subset of patients currently participating in the OLE study in order to steer further development in Fabry disease. In parallel, Idorsia is working with regulatory authorities to design the next Phase 3 study to evaluate the effect of lucerastat on renal function. About IdorsiaIdorsia Ltd is reaching out for more – We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 25-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America – the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 750 highly qualified specialists dedicated to realizing our ambitious targets. For further information, please contactAndrew C. WeissSenior Vice President, Head of Investor Relations & Corporate CommunicationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.commedia.relations@idorsia.com www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF

Phase 3Drug ApprovalClinical Result

30 Sep 2024

·www.pharmaceutical-technology.com

J&J clinches EC approval for first single-pill PAH combo

The European Commission has approved Johnson and Johnson’s Yuvanci for pulmonary arterial hypertension, offering the first single-pill treatment option to European patients. Credit: andreswd via Getty Images. The European Commission (EC) has approved Johnson and Johnson’s Yuvanci (macitentan + tadalafil) for the treatment of pulmonary arterial hypertension (PAH). The approval marks Yuvanci as the only single-tablet combination therapy available for patients with PAH. PAH is a rare, progressive disorder in which patients have high blood pressure in the pulmonary arteries for no apparent reason. Current treatment for PAH involves first-line dual combination therapy with macitentan and tadalafil for patients without cardiopulmonary comorbidities. This currently consists of a multi-pill regimen. “This can deeply impact their [PAH patients’] daily lives as they might struggle to maintain adherence to their treatment regimen,” said Dr. Tamara Werner-Kiechle, the Europe, Middle East, and Africa (EMEA) therapeutic area lead for neuroscience and cardiopulmonary drugs at Johnson & Johnson Innovative Medicine in a 30 September press release. Johnson and Johnson has developed the Yuvanci as a substitution therapy for the long-term treatment of PAH in adults of the World Health Organization’s (WHO) Functional Class (FC) II to III. This includes patients with PAH that causes a slight limitation in physical activity, yet they are still comfortable at rest, and “patients with marked limitations to physical activity”, as per WHO. Patients will need to have already been treated with a two-pill combination of macitentan and tadalafil to be eligible for Yuvanci. Johnson and Johnson currently markets macitenan monotherapy under the brand name Opsumit, whilst Eli Lilly sells tadalafil as Cialis for PAH. The approval is based on data from the Phase III A DUE study (NCT03904693) , which also led to a positive recommendation for Yuvanci’s approval by the European Medicines Agency’s (EMA) Committee for Human Medicinal Products in July. The pharmaceutical giant presented data from the Phase III A DUE clinical study at the American College of Cardiology’s 72nd Annual Scientific Session. In the double-blind study, Yuvanci-treated patients showed significant improvements in the co-primary endpoints of pulmonary vascular resistance (PVR) and pulmonary haemodynamic improvement. Patients who took the combination therapy demonstrated a 44% decrease in PVR compared to a 22% decrease in the Adcirca monotherapy group. See Also: Almac Group North American Headquarters Expansion, Pennsylvania, USA LOTTE BIOLOGICS’ East Syracuse Pharmaceutical Manufacturing Facility, US Opsumit is an endothelin receptor antagonist that treats PAH by inhibiting pathways related to vasoconstriction, fibrosis and proliferation. Meanwhile, Cialis is a phosphodiesterase type-5 inhibitor that treats the disorder by increasing cGMP, leading to a relaxation of the pulmonary vascular smooth muscle cell and vasodilation of the pulmonary vascular bed. Johnson and Johnson submitted a new drug application to the US Food and Drug Administration (FDA) for Yuvanci in May 2023, receiving an approval for its submission in March 2024.

Clinical ResultPhase 3Drug Approval

100 Deals associated with Bosentan

External Link

KEGG	Wiki	ATC	Drug Bank
D01227	Bosentan	C02KX01	DB00559

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Ulcer	JP	Actelion Pharmaceuticals Ltd.	24 Aug 2015
Idiopathic pulmonary arterial hypertension	EU	Janssen-Cilag International NV	24 Jun 2013
Idiopathic pulmonary arterial hypertension	IS	Janssen-Cilag International NV	24 Jun 2013
Idiopathic pulmonary arterial hypertension	LI	Janssen-Cilag International NV	24 Jun 2013
Idiopathic pulmonary arterial hypertension	NO	Janssen-Cilag International NV	24 Jun 2013
Scleroderma associated digital ulcer	EU	Janssen-Cilag International NV	14 May 2002
Scleroderma associated digital ulcer	IS	Janssen-Cilag International NV	14 May 2002
Scleroderma associated digital ulcer	LI	Janssen-Cilag International NV	14 May 2002
Scleroderma associated digital ulcer	NO	Janssen-Cilag International NV	14 May 2002
Pulmonary Arterial Hypertension	US	Actelion Pharmaceuticals US, Inc.	20 Nov 2001

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Persistent Fetal Circulation Syndrome	Phase 3	US	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	AU	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	BE	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	CZ	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	FR	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	DE	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	PL	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	RU	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	SG	Actelion Pharmaceuticals US, Inc.	01 Dec 2011
Persistent Fetal Circulation Syndrome	Phase 3	KR	Actelion Pharmaceuticals US, Inc.	01 Dec 2011

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EADV2023	Not Applicable	Vascular Diseases	-	Bosentan 62.5 mg	rovhabhuyq(xsstvophui): mean treatment effect = 35.6 (95% CI, 13.4 - 57.7), P-Value = <0.05 View more	Positive	11 Oct 2023
				Nifedipine 20 mg
EULAR2019	Not Applicable	Scleroderma, Systemic	35	Bosentan	edwezakesk(ttvicueumi) = yxgehnynfm ltryjdvxta (qyuaefuhae ) View more	Positive	12 Jun 2019
ERS2018	Not Applicable	Pulmonary Arterial Hypertension	-	Bosentan	grgfljngfk(kjgghlnnyp) = izgcvadxkz nqdcxyyvvi (txqwcjrwjs ) View more	Positive	15 Sep 2018
				Macitentan	grgfljngfk(kjgghlnnyp) = desmmamfok nqdcxyyvvi (txqwcjrwjs ) View more
EULAR2018	Not Applicable	Scleroderma, Systemic Endothelin-1 (ET-1)	-	ILO group	ojwakexdna(zcwwawnqxi) = lfdbatodiv sgyqwthuwn (ubegrwlzee )	Positive	13 Jun 2018
				ILO +BOS group	ojwakexdna(zcwwawnqxi) = klrskbkchh sgyqwthuwn (ubegrwlzee )
ESC2018	Not Applicable	Hypertension, Pulmonary	50	Pulmonary artery vasodilators	badmhwxnhd(wskovmcweb) = zpiosomncd ukoojywfas (cvsojxensc ) View more	Negative	27 May 2018
NCT00433329 (COMPASS-3, Pubmed \| Pulm Circ)	Phase 4	Pulmonary Arterial Hypertension Add-on	100	Bosentan monotherapy	mrlxpkryhw(ctprwavxcy) = keeohbxrui ljlqmoeszu (evrkpmjdfu )	-	01 Jan 2018
				Add-on sildenafil	mrlxpkryhw(ctprwavxcy) = gqkcckgopg ljlqmoeszu (evrkpmjdfu )
NCT01338415 (FUTURE 3 Ext, CTgov)	Phase 3	Pulmonary Arterial Hypertension	58	Bosentan (Bosentan 2mg/kg b.i.d.)	vlvcxwpkhh(qivodyjomb) = opwdbnjykw kblmeostkl (yfdcbdvxkg, omemjnlrul - msmnubybuk) View more	-	11 Dec 2017
				Bosentan (Bosentan 2mg/kg t.i.d.)	vlvcxwpkhh(qivodyjomb) = jedltcbpof kblmeostkl (yfdcbdvxkg, vsovtoxwes - olehpttmie) View more
NCT00323297 (Pubmed)	Phase 4	Pulmonary Arterial Hypertension	105	Sildenafil	qfhipwhdga(ybzwbnwfmn) = lcobmpvpbf svuwpduklc (acvcwbwonv )	-	06 Sep 2017
				Placebo	qfhipwhdga(ybzwbnwfmn) = bbcriuiqyt svuwpduklc (acvcwbwonv )
ERS2017	Not Applicable	Pulmonary Arterial Hypertension \| Chronic thromboembolic pulmonary hypertension	2	Bosentan 62.5mg/d for 4w, then 125mg/d	macvcsjlce(uqrvnoqbsk) = ltdxjyookm ivnugxifex (esbpfbxrao ) View more	Positive	01 Sep 2017
ESC2017	Not Applicable	Hypertension, Pulmonary	-	Bosentan	efsfhlfyen(nfnycspkwr) = nehixfzlmv dvrfmieigm (hafyqnhabb ) View more	-	29 Aug 2017
				bosentan	efsfhlfyen(nfnycspkwr) = alepvmspha dvrfmieigm (hafyqnhabb ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis