The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach).
The investigators are also evaluating new biomarker steroids to reflect adequate osilodrostat dosing, the durability and safety, and clinical improvement during treatment.

Start Date19 Jul 2024

Sponsor / Collaborator

University of Michigan

[+1]

NCT06131580 / Active, not recruitingPhase 4IIT

Continuation of an Open-label, Multi-center Study to Assess Long Term Safety in Canadian Patients With Endogenous Cushing's Syndrome Who Have Completed Prior Recordati-sponsored Osilodrostat (LCI699) Study LCI699C2X01B and Are Judged by the Investigator to Benefit From Continued Treatment With Osilodrostat

The purpose of this study is to continue the evaluation of long-term safety of osilodrostat in 7 Canadian patients who have already received osilodrostat treatment in a previous Global Recordati-sponsored roll-over study and who, based on investigators' judgement, will continue benefiting with its administration.

Start Date24 Oct 2023

Sponsor / Collaborator

Recordati Rare Diseases

NCT05633953 / CompletedNot Applicable

A Retrospective Observational Study to Evaluate the Safety and Effectiveness of Osilodrostat for the Treatment of Non-Cushing's Disease Cushing's Syndrome (LINC7)

This is a multi-centre, observational, non-comparative, retrospective cohort study designed to evaluate the long-term safety and effectiveness of osilodrostat in non-CD CS patients. Patients treated with oral osilodrostat regardless of the duration of their treatment will be followed retrospectively for up to 36 months after initiating osilodrostat.

Start Date16 Jan 2023

Sponsor / Collaborator-

100 Clinical Results associated with Osilodrostat Phosphate

100 Translational Medicine associated with Osilodrostat Phosphate

100 Patents (Medical) associated with Osilodrostat Phosphate

111

Literatures (Medical) associated with Osilodrostat Phosphate

26 Nov 2024·Journal of the Endocrine Society

Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol

Article

Author: Newell-Price, John ; Gadelha, Mônica R ; Feelders, Richard A ; Heaney, Anthony P ; Lacroix, André ; Biller, Beverly M K ; Pivonello, Rosario ; Piacentini, Andrea ; Fleseriu, Maria ; Witek, Przemysław ; Pedroncelli, Alberto M

Abstract:

Purpose:

To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone.

Methods:

Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled.

Results:

Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, −7.4%/−4.9%, −6.0%/−5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, −5.0%, −4.8%, and 1.9%; glycated hemoglobin, −5.1%, −4.8%, and −1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL.

Conclusion:

In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes.

Clinical trial identifiers:

NCT02180217 (LINC 3); NCT02697734 (LINC 4)

16 Sep 2024·Bioanalysis

Quantification of osilodrostat in horse urine using LC/ESI–HRMS to establish an elimination profile for doping control

Article

Author: Mizobe, Fumiaki ; Takemoto, Shunsuke ; Nagata, Shun-ichi ; Shigematsu, Ryo ; Yamada, Masayuki ; Ishii, Hideaki ; Leung, Gary Ngai-Wa ; Tanabe, Sohei ; Kunii, Hirokazu ; Ishikawa, Yuhiro ; Nomura, Motoi ; Arima, Daisuke ; Yuasa, Reiko ; Yamanaka, Takashi

Aim: The use of osilodrostat, developed as a medication for Cushing's disease but categorized as an anabolic agent, is banned in horses by both the International Federation of Horseracing Authorities and the Fédération Equestre Internationale. For doping control purposes, elimination profiles of hydrolyzed osilodrostat in horse urine were established and the detectability of free forms of osilodrostat and its major metabolite, mono-hydroxylated osilodrostat (M1c), was investigated.Materials & methods: Post-administration urine samples obtained from a gelding and three mares were analyzed to establish the elimination profiles of osilodrostat using a validated method involving efficient enzymatic hydrolysis followed by LC/ESI-HRMS analysis.Results: Applying the validated quantification method with an LLOQ of 0.05 ng/ml, hydrolyzed osilodrostat could be quantified in post-administration urine samples from 48 to 72 h post-administration; by contrast, both hydrolyzed osilodrostat and M1c were detected up to 2 weeks. In addition, confirmatory analysis identified the presence of hydrolyzed osilodrostat for up to 72 h post-administration.Conclusion: For doping control purposes, we recommend monitoring both hydrolyzed M1c and osilodrostat because of the greater detectability of M1c and the availability of a reference material of osilodrostat, which is essential for confirmatory analysis.

01 Sep 2024·CURRENT DRUG METABOLISM

Metabolic Pathway of Osilodrostat in Equine Urine Established through High-resolution Mass Spectrometric Characterization for Doping Control

Article

Author: Mizobe, Fumiaki ; Takemoto, Shunsuke ; Shigematsu, Ryo ; Nagata, Shun-ichi ; Yamada, Masayuki ; Ishii, Hideaki ; Leung, Gary Ngai-Wa ; Tanabe, Sohei ; Kunii, Hirokazu ; Ishikawa, Yuhiro ; Nomura, Motoi ; Arima, Daisuke ; Yuasa, Reiko ; Yamanaka, Takashi

Objective::

Osilodrostat, used to treat Cushing's disease, exhibits an anabolic effect, leading to its classification as a prohibited substance in horseracing and equestrian sports. This study reports the characterization of osilodrostat metabolites in horse urine and elucidates its metabolic pathways for the first time for doping control purposes.

Methods::

Osilodrostat was administered nasoesophageally to four thoroughbreds (one gelding and three mares) at a dose of 50 mg each. Potential metabolites were extensively screened via our developed generic approach employing differential analysis to identify metabolites. Specifically, high-resolution mass spectral data were compared between pre- and post-administration samples on the basis of criteria of fold-changes of peak areas and their P values. Potential metabolite candidates were further identified through mass spectral interpretations using product ion scan data.

Results::

A total of 37 metabolites were identified after comprehensive analysis. Osilodrostat was predominantly metabolized into a mono-hydroxylated form M1c (~40%) alongside osilodrostat glucuronide M2 (~17%). Given their longest detection time (2 weeks after administration) and the identification of several conjugates of osilodrostat and M1c, including a novel conjugate of riburonic acid, we recommend monitoring both osilodrostat and M1c after hydrolysis during the screening stage. However, only osilodrostat can be used for confirmation because of the availability of a reference material.

Conclusion::

It is advisable to screen for both osilodrostat and its mono-hydroxylated metabolite M1c to effectively monitor horse urine for the potential misuse or abuse of osilodrostat. For suspicious samples, confirmation of osilodrostat using its reference material is required.

News (Medical) associated with Osilodrostat Phosphate

08 Nov 2024

·www.globenewswire.com

RECORDATI: CONTINUED DOUBLE-DIGIT GROWTH IN THE FIRST NINE MONTHS OF 2024 - REVENUE +12.0%, EBITDA(1) +11.8%, ADJUSTED NET INCOME(2) +9.5%

Consolidated net revenue of € 1,743.1 million in the first nine months, +12.0% or +9.3% on a like-for-like basis(3) and at constant exchange rates (CER)EBITDA(1) of € 665.7 million, +11.8%, revenue margin of 38.2% Adjusted net income(2) of € 445.4 million, +9.5% Net income of € 338.4 million, +11.1% Free cash flow(4) at € 434.3 million, +€ 42.5 million vs prior yearNet debt(5) at € 1,317.3 million, just below 1.6x EBITDAFinancial targets for FY 2024 confirmed, excluding any potential contribution from Enjaymo® Global Rare Diseases business to be further strengthened by announced agreement with Sanofi to acquire the global rights to Enjaymo®; deal expected to close by end of 2024, subject to regulatory approvals Isturisa®approved in China for the treatment of adult patients with Cushing syndromeResolution to distribute an interim 2024 dividend of € 0.60 per shareApproval of a new share buy-back program to service the stock option and performance shares plans Milan, November 8th, 2024 – The Board of Directors of Recordati S.p.A. approved the Group’s Interim Report on 30th September 2024, representing additional voluntary financial reporting (6). The Report was prepared using the assessment, measurement and recognition criteria prescribed by international accounting standards (IFRS). The Group’s Interim Report dated 30th September 2024 will be available on 11th November at the company’s offices and on the company’s website (www.recordati.com) and can also be viewed on the authorized storage system 1Info (www.1Info.it). Rob Koremans, Chief Executive Officer of Recordati, commented: “During the first nine months, we delivered double-digit revenue and profit growth, reflecting the strong performance across the business with more patients benefiting from our therapies. These results reflect the continued commitment of all our people, who are instrumental to our success. With a positive outlook for the remainder of the year, we are well positioned to achieve our upgraded financial objectives for FY 2024. Together, we will continue to build on our momentum and create lasting value for our stakeholders. “I am also pleased to highlight our recent agreement with Sanofi to acquire the global rights to Enjaymo®, the only approved treatment option for patients with cold agglutinin disease. This transaction will reinforce our strong commitment to serving patients with rare diseases and is a strong strategic fit to our portfolio, bringing a product with a robust profile, supported by a strong team, with attractive financial contributions expected on both the top and bottom lines.” Financial highlights Consolidated net revenue for the first nine months of 2024 was € 1,743.1 million, up 12.0% versus the first nine months of 2023 or 9.3% on a like-for-like(3) basis at CER. This was driven by strong business momentum across both Specialty & Primary Care and Rare Diseases. The adverse FX impact for the first nine months of 2024 was € 35.9 million (-2.3%), mainly driven by the devaluation of the Turkish lira, particularly in the first and third quarters, which was compensated by high price inflation in Türkiye. Specialty & Primary Care revenue totaled € 1,094.4 million in the first nine months of 2024, growing 11.1% or 6.5% on a like-for-like(3) basis at CER (+2.6% excluding Türkiye). This reflects a particularly strong performance from the Urology franchise with 51.4% growth versus the previous year, driven by the double-digit growth of Eligard® and the € 82.9 million contribution of Avodart® and Combodart®/Duodart®(7) (versus € 3.8 million in the third quarter of 2023). The Cardiovascular and Gastrointestinal franchises remained resilient and delivered slight growth, while the Cough and Cold business reflected solid in-market performance in the context of a softer flu season as compared to the previous year.Rare Diseases revenue totaled € 605.6 million in the first nine months of 2024, up 14.1% as compared to the first nine months of 2023, or 14.5% at CER, driven by the key growth franchises of Oncology and Endocrinology which continue to show substantial further growth potential. The Endocrinology franchise achieved net revenue of € 239.4 million, an increase of 36.0% and reflecting the continued strong performance of Isturisa® and double-digit growth of Signifor®. The Oncology franchise achieved net revenue of € 175.9 million, an increase of 17.1%, driven by double-digit growth from both Qarziba® and Sylvant®. The Metabolic franchise achieved net revenue of € 190.2 million, a decrease of 6.9%, mainly due to generic competition for Carbaglu® in the US and EMEA, with growth in other international markets. Adjusted operating income(8) was € 539.5 million for the first nine months of 2024, up 9.7% over the previous year, and 31.0% of net revenue versus 31.6% in the same period last year. Operating income was € 504.1 million in the first nine months of 2024, up 14.9% over the first nine months of 2023, absorbing gross margin-related non-cash charges of € 28.1 million (versus € 47.2 million in first nine months of 2023), arising from the unwind of the fair value step up of the acquired rare oncology inventory. Non-recurring costs were € 7.3 million in the first nine months of 2024, versus € 5.4 million in the first nine months of 2023, which includes € 2.5 million related to the agreement with Sanofi for the global rights to Enjaymo®.EBITDA(1) was € 665.7 million for the first nine months of 2024, up 11.8% compared to the first nine months of 2023, with margin of 38.2% of net revenue, in line with the previous year. Strong revenue and operating leverage were, in part, offset by a reduction in adjusted gross profit margin due to the consolidation of Avodart® and Combodart®/ Duodart® and product mix.Financial expenses were € 62.3 million, up by € 13.3 million compared to the previous year, including € 2.8 million in FX losses (mostly unrealized, compared to losses of € 0.3 million in the first nine months of 2023) and € 3.9 million of net monetary losses from hyperinflation accounting (compared to a gain of € 1.8 million in the first nine months of 2023). Adjusted net income(2) was € 445.4 million, 25.6% of revenue, up by 9.5% compared to the same period of 2023, with higher adjusted operating income partially offset by an increase in financial expenses and a higher tax rate, following a statutory tax rate increase in some countries. Net income was € 338.4 million, 19.4% of revenue, an increase of 11.1% versus first nine months of 2023, with the higher tax rate and financing expenses offsetting the higher operating income. Free cash flow(4) was € 434.3 million for the first nine months of 2024, an increase of € 42.5 million versus the the first nine months of 2023, driven by higher EBITDA which was slightly offset by higher interests and income taxes paid. Net debt(5) as of 30th September 2024 was € 1,317.3 million, or leverage of just below 1.6x EBITDA(6), compared to net debt of € 1,579.4 million on 31st December 2023. Shareholders’ equity was € 1,876.1 million. Pipeline and Corporate Development The Isturisa® new drug application (NDA) was approved by the China National Medical Products Administration (NMPA) in September for the treatment of adult patients with Cushing syndrome. On October 4th, the Group announced an agreement with Sanofi to acquire the global rights to Enjaymo®, a biologic which is the only approved targeted product for the treatment of cold agglutinin disease (CAD), a rare B-cell lymphoproliferative disorder. In 2022, Enjaymo® was granted approval by the U.S. Food and Drug Administration (FDA), the European Commission (EC) and the Japanese Ministry of Health, Labor and Welfare. Enjaymo® generated approximately € 100 million in revenue over the last 12 months as of August 2024 and is expected to generate revenue in excess of € 150 million in FY 2025, with peak sales potential of € 250-300 million. The transaction is expected to be immediately accretive at the EBITDA level, with margin above the current Rare Diseases average as of 2025. Under the terms of the agreement, Recordati will make an upfront payment of US$ 825 million and additional commercial milestone payments of up to US$ 250 million if net sales reach certain thresholds at or above the top end of peak year sales expectations. The transaction is expected to close by the end of 2024, subject to regulatory clearances (see also press release issued on October 4th 2024). The deal will be funded by existing cash and new committed bank debt facilities. Business outlook Thanks to continued strong momentum, the Group is on track to deliver the targets for FY 2024 as adjusted upward on July 30th (excluding any potential contribution from Enjaymo®): Net revenue between € 2,300 and € 2,340 millionEBITDA(1) between € 845 and € 865 million; margin of +/- 37%Adjusted net income(2) between € 560 and € 580 million; margin of +/- 24.5%Minimal contribution expected from Enjaymo®, subject to timing of regulatory approvals Additional resolutions Interim dividend 2024 The Board of Directors passed a resolution to distribute an interim 2024 dividend to shareholders of € 0.60 (gross of tax withholdings) per share outstanding at the ex-dividend date, thus excluding treasury stock held in the Company’s portfolio on that date. The 2024 interim dividend will be payable as of 20th November 2024 (record date 19th November 2024), with coupon no. 34, to shareholders registered on 18th November 2024. The Independent Auditor EY S.p.A. has issued the opinion required by Art. 2433 – bis, paragraph 5 of the Italian Civil Code, which is available at the company’s offices. The Directors’ Report and Recordati S.p.A. financial statements as of 30th June 2024, based on which the latter’s Board of Directors resolved the distribution of the interim dividend, are available at the company’s office and website (www.recordati.com), and can also be viewed on the authorized storage system 1Info (www.1Info.it). Limited assurance on sustainability reporting In compliance with the Italian Legislative Decree No. 125/2024 – transposing in Italy the EU Directive No. 2022/2464 on Corporate Sustainability Reporting (so called “CSRD”) – the Board of Directors, upon proposal of the Board of Statutory Auditors, has resolved to integrate – starting from this financial year 2024 - the mandate for activities regarding the limited assurance attestation on sustainability reporting, set forth by the aforementioned decree, to Ernst & Young S.p.A., by extending to such activities the current engagement granted by the Shareholders Meeting held on 29th April 2020 with respect to the attestation of the non-financial disclosure. Appointment of the new Financial Reporting Officer pursuant to art.154-bis of TUF The Board of Directors has appointed, until revocation and upon favourable opinion of the Board of Statutory Auditors Niccolo Giovannini - VP Group Finance, reporting to Luigi La Corte, Group Chief Financial Officer - as Financial Reporting Officer pursuant to art.154-bis of TUF and art.25 of the Articles of Association. The appointment is effective as of today, following the approval of Group’s Interim Report on 30th September 2024. Approval of a new share buy-back program to service the stock option and performance shares plans Today, the Board of Directors has also approved the launch of a new share buy-back program under art. 5 of (EU) Regulation no. 596/2014 for a maximum of 1,500,000 ordinary shares with a maximum cash outlay of € 90,000,000. This implements the resolution adopted by the Shareholders’ meeting held on 22nd April 2024 to purchase Recordati ordinary shares in order to service current and future stock option/performance shares plans in favour of the Recordati Group’s management or share-based incentive plans that might be approved by the Company in the future. All details required by the applicable regulations on the launch of the share buy-back program - whose start is envisaged on 12th November 2024 until 15th April 2025, following the end of the current buyback programme envisaged by 11th November 2024 as announced on 9th May 2024 - will be included in a specific press release that will be issued according to law and to which reference is made. (1) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3. (2) Net income excluding the amortization and write-down of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory pursuant to IFRS 3, and monetary net gains/losses from hyperinflation (IAS 29), net of tax effects. (3) Pro-forma growth calculated excluding revenue of Avodart® and Combodart®/ Duodart® for both 2024 and 2023.(4) Total cash flow excluding financing items, milestones, dividends, purchases of treasury shares net of proceeds from exercise of stock options.(5) Cash and cash equivalents, less bank debts and loans, which include the measurement at fair value of hedging derivatives. (6) Please note that Italian Legislative Decree 25/2016, which implements Directive 2013/50/EU, no longer stipulates the submission of an interim management report, which was previously required in terms of paragraph 5 of Art. 154- ter of Italian Legislative Decree 58/1998.(7) Trademarks are owned by or licensed to the GSK group of companies. Transition of commercialization effectively concluded.(8) Net income before income taxes, financial income and expenses and non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3. Conference Call Recordati will host a conference call today, November 8th at 4:00 p.m. CET (3:00 p.m. GMT) to present the results for the first nine months of 2024. The dial-in numbers for the conference call service are: Italy + 39 02 802 09 11, toll free 800 231 525UK + 44 1 212818004, toll free (44) 0 800 0156371USA +1 718 7058796, toll free (1) 1 855 2656958France +33 1 70918704Germany +49 6917415712 Participants are invited to dial in 10 minutes before conference time. If conference operator assistance is required to connect, please dial *0. The slides that will be referenced during the call will be available at www.recordati.com under Investors/Company Presentations. The audio conference live webcast will also be available at the following link Recordati is an international pharmaceutical group listed on the Italian Stock Exchange (XMIL: REC), with roots dating back to a family-run pharmacy in Northern Italy in the 1920s. We are uniquely structured to provide treatments across specialty and primary care, and rare diseases. Our fully integrated operations span clinical development, chemical and finished product manufacturing, commercialization and licensing. We operate in approximately 150 countries across EMEA, the Americas and APAC with over 4,450 employees. We believe that health is a fundamental right, not a privilege. Today, our purpose of “unlocking the full potential of life” aims at empowering individuals to live life to the fullest, whether addressing common health challenges or the rarest. Investor Relations Eugenia Litz +44 7824 394 750 investorelations@recordati.itGianluca Saletta +39 348 979 4876 investorelations@recordati.itMedia Relations ICR Healthcare US:Alexis Feinberg +1 203 939 2225 recordatiuspr@westwicke.com UK, Europe & Rest of World:Jessica Hodgson +44 7561 424 788recordati@consilium-comms.com This document contains forward-looking statements relating to future events and future operating, economic and financial results of the Recordati group. By their nature, forward-looking statements involve risk and uncertainty because they depend on the occurrence of future events and circumstances. Actual results may therefore differ materially from those forecast for a variety of reasons, most of which are beyond the Recordati group’s control. The information on the pharmaceutical specialties and other products of the Recordati group contained in this document is intended solely as information on the activities of the Recordati Group, and, as such, it is not intended as a medical scientific indication or recommendation, or as advertising. RECORDATI GROUP Summary of the consolidated results,prepared in accordance with International Financial Reporting Standards (IFRS)(€ thousands) INCOME STATEMENTFirst nine months 2024First nine months 2023Change %NET REVENUE1,743,0811,556,17412.0Cost of sales(556,171)(490,495)13.4GROSS PROFIT1,186,9101,065,67911.4Selling expenses(360,709)(345,506)4.4Research and development expenses(204,849)(182,239)12.4General and administrative expenses(110,014)(93,630)17.5Other income/(expenses), net(7,240)(5,553)30.4OPERATING INCOME504,098438,75114.9Financial income/(expenses), net(62,319)(49,054)27.0PRE-TAX INCOME441,779389,69713.4Income taxes(103,379)(85,205)21.3NET INCOME 338,400304,49211.1Adjusted gross profit (1)1,214,9861,113,1679.1Adjusted operating income (2)539,518491,6089.7Adjusted net income (3)445,361406,5669.5EBITDA (4)665,666595,57311.8Net income attributable to: Equity holders of the Parent338,400304,49211.1Non-controlling interests00n.s.EARNINGS PER SHARE (euro) Basic(5)1.6401.48110.7Diluted(6)1.6181.45611.1(1) Gross profit adjusted from impact of non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3. (2) Net income before income taxes, financial income and expenses, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3.(3) Net income excluding amortization and write-downs of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3) and monetary net gains/losses from hyperinflation (IAS 29), net of tax effects.(4) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory according to IFRS 3.(5) Earnings per share (EPS) are based on average shares outstanding during the respective period, 206.299.160 in 2024 and 205.421.410 in 2023. These amounts are calculated deducting treasury shares in the portfolio, the average of which was 2.825.996 shares in 2024 and 3.703.746 shares in 2023.(6) Diluted earnings per share is calculated by taking into account rights granted to employees.COMPOSITION OF NET REVENUEFirst nine months 2024First nine months 2023Change % Total revenue1,743,0811,556,17412.0 Italy258,631234,30410.4 International1,484,4501,321,87012.3 RECORDATI GROUP(€ thousands) Reconciliation of Net income to EBITDA(1) First nine months 2024First nine months 2023Net income338,400304,492Income taxes103,37985,205Financial income/(expenses), net62,31949,054Non-recurring expenses7,3445,369Non-cash charges from PPA inventory uplift28,07647,488Adjusted operating income(2)539,518491,608Depreciation, amortization and write-downs126,148103,965EBITDA(1)665,666595,573 Reconciliation of Net income to Adjusted Net income(3) First nine months 2024First nine months 2023Net income338,400304,492Amortization and write-downs of intangible assets(excluding software)100,15781,180Tax effect(22,619)(17,405)Non-recurring operating expenses7,3445,369Tax effect(1,943)(1,340)Non-cash charges from PPA inventory uplift28,07647,488Tax effect(7,019)(11,881)Monetary net (gain)/losses from hyperinflation (IAS29)3,900(1,759)Tax effect(935)422Adjusted net income(3)445,361406,566 (1) Net income before income taxes, financial income and expenses, depreciation, amortization and write-downs of property, plant and equipment, intangible assets and goodwill, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3).(2) Net income before income taxes, financial income and expenses, non-recurring items and non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3).(3) Net income excluding amortization and write-downs of intangible assets (except software) and goodwill, non-recurring items, non-cash charges arising from the allocation of the purchase price of EUSA Pharma to the gross margin of acquired inventory (IFRS 3) and monetary net gains/losses from hyperinflation (IAS 29), net of tax effects. RECORDATI GROUPSummary of the consolidated results, prepared in accordance with International Financial Reporting Standards (IFRS)(€ thousands) ASSETS30.09.202431.12.2023Property, plant and equipment187,848178,657Intangible assets1,847,7041,938,197Goodwill789,123778,350Other equity investments and securities16,86521,555Other non-current assets13,87112,458Deferred tax assets92,56776,674TOTAL NON-CURRRENT ASSETS2,947,9783,005,891 Inventories410,107404,831Trade receivables474,514445,193Other receivables102,46699,401Other current assets26,78219,924Derivative instruments measured at fair value6,71011,079Cash and cash equivalents235,020221,812TOTAL CURRENT ASSETS1,255,5991,202,240TOTAL ASSETS4,203,5774,208,131 RECORDATI GROUPSummary of the consolidated results, prepared in accordance with International Financial Reporting Standards (IFRS)(€ thousands) EQUITY AND LIABILITIES30.09.202431.12.2023 Share capital26,14126,141Share premium reserve83,71983,719Treasury shares(139,881)(127,970)Reserve for derivative instruments(2,180)(286)Translation reserve(301,627)(264,700)Other reserves61,53761,219Profits carried forward1,809,9971,636,451Net income338,400389,214Interim dividend0(117,396)Shareholders’ equity attributable to equity holders of the Parent1,876,1061,686,392Shareholders’ equity attributable to non-controlling interests00TOTAL SHAREHOLDERS’ EQUITY1,876,1061,686,392 Loans - due after one year1,264,8841,353,216Provisions for employee benefits21,40521,239Deferred tax liabilities134,488144,208TOTAL NON-CURRENT LIABILITIES1,420,7771,518,663 Trade payables276,907263,979Other payables198,213174,407Tax liabilities100,73867,110Other current liabilities4,6165,307Provisions for risks and charges19,24116,596Derivative instruments measured at fair value14,21219,993Loans - due within one year270,337355,752Short-term debts to banks and other lenders22,43099,932TOTAL CURRENT LIABILITIES906,6941,003,076TOTAL SHAREHOLDERS’ EQUITY AND LIABILITIES4,203,5774,208,131 RECORDATI GROUPSummary of consolidated results prepared in accordance with International Financial Reporting Standards (IFRS) (€ thousands) CASH FLOW STATEMENTFirst nine months 2024First nine months 2023OPERATING ACTIVITIES Net income338,400304,492Income taxes103,37985,206Net interest54,41848,158Depreciation of property, plant and equipment24,00321,577Amortization of intangible assets97,59182,304Write-downs4,55484Equity-settled share-based payment transactions10,1207,515Other non-monetary components41,06955,772Change in other assets and other liabilities(11,985)(20,538)Cash flow generated/(used) by operating activities before change in working capital661,549584,570Change in: - inventories(41,813)(31,681)- trade receivables(36,418)(73,753)- trade payables14,22330,082Change in working capital(64,008)(75,352)Interest received4,0073,923Interest paid(64,284)(50,314)Income taxes paid(82,634)(53,282)Cash flow generated/(used) by operating activities454,630409,545INVESTMENT ACTIVITIES Investments in property, plant and equipment(21,743)(17,998)Disposals of property, plant and equipment1,385329Investments in intangible assets(15,377)(345,597)Disposals of intangible assets2,351287Sale of non-current assets held for sale2,0003,000Cash flow generated/(used) by investment activities(31,384)(359,979)FINANCING ACTIVITIES Opening of loans144,872348,256Repayment of loans(320,185)(214,701)Payment of lease liabilities(8,311)(8,116)Change in short-term debts to banks and other lenders(71,722)(45,008)Dividends paid(130,220)(129,071)Purchase of treasury shares(78,087)(6,483)Sale of treasury shares52,74419,681Cash flow generated/(used) by financing activities(410,909)(35,442)Change in cash and cash equivalents12,33714,124Opening cash and cash equivalents221,812284,734Currency translation effect8713,422Closing cash and cash equivalents235,020302,280 DECLARATION BY THE FINANCIAL REPORTING OFFICERThe Financial Reporting Officer, Luigi La Corte, declares, pursuant to paragraph 2 of Article 154-bis of the Consolidated Law on Finance, that the accounting information contained in this press release corresponds to the Company’s documentation, books and accounting records.

Executive ChangeFinancial StatementDrug ApprovalAcquisition

31 Aug 2022

·www.biospace.com

RECORDATI RARE DISEASES ANNOUNCES PUBLICATION OF LONG-TERM OUTCOMES FROM THE EXTENSION TO THE PHASE III LINC 3 STUDY OF ISTURISA® (OSILODROSTAT) IN PATIENTS WITH CUSHING'S DISEASE IN THE EUROPEAN JOURNAL OF ENDOCRINOLOGY

Long-term findings from the multicenter, international LINC 3 study demonstrated that treatment with ISTURISA® (osilodrostat) maintained cortisol normalization and was well tolerated in most patients with Cushing's disease. LEBANON, N.J., Aug. 31, 2022 /PRNewswire/ -- Recordati Rare Diseases Inc. announces the publication of the long-term outcomes from the open-label extension period of the Phase III LINC 3 study of ISTURISA in The European Journal of Endocrinology.1 These data support the long-term utility of ISTURISA in the maintenance treatment of patients with Cushing's disease and reinforce ISTURISA as an effective and well-tolerated oral therapy. ISTURISA is indicated in the United States for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.2 Cushing's disease is a rare and debilitating condition of hypercortisolism that is caused by a pituitary adenoma.3 The Phase III LINC 3 study was the largest prospective trial of an adrenal steroidogenesis inhibitor to date. In total, 106 of the 113 patients who completed the 48-week core phase opted to continue receiving open-label ISTURISA during the extension phase, which ended after all patients completed ≥72 weeks of treatment or had discontinued the study. Median duration of exposure to ISTURISA from core study baseline to end of the extension was 130 weeks (range 1–245). Key findings published in the manuscript entitled 'Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension' include:1 The normalization in mean urinary free cortisol (mUFC) achieved during the core phase was maintained, with mean mUFC ≤ upper limit of normal (ULN) throughout the extension; at week 72, 86/106 (81.1%) patients had mUFC ≤ULN The median average ISTURISA dose from core study start to end of the extension was 7.4 mg/day (range 0.8–46.6); dose received stabilized during the extension, indicating that ISTURISA treatment provided a sustained response without need for up-titration over time. Observed improvements in most cardiovascular and metabolic-related parameters associated with Cushing's disease at the end of the core study were maintained or further improved with long-term treatment. Patient-reported quality of life (QoL) scores (CushingQoL and Beck Depression Inventory) also continued to improve during long-term treatment. Improvements in physician-rated severity scores for physical manifestations of hypercortisolism were evident within 12 weeks of ISTURISA treatment; the proportion of patients rated with an improvement was maintained or increased with longer follow-up, including improvement in hirsutism in female patients. In female patients, estradiol and testosterone levels tended to return to baseline levels with longer follow-up. ISTURISA was well tolerated in most patients, with no unexpected adverse events (AEs) compared with that observed in the core phase; AEs of special interest including hypocortisolism-related and adrenal hormone precursor-related AEs were generally less frequently reported during the extension phase than the core. The most common AEs regardless of study drug relationship were nausea (45.3%), headache, (36.5%) and fatigue (32.8%). "Findings from our large trial, where patients with Cushing's disease opted to continue treatment with osilodrostat during the extension, support osilodrostat as an effective, long-term treatment option for patients with this chronic disease," said Maria Fleseriu, Professor of Medicine (Endocrinology) and Neurological Surgery and Director of the Pituitary Center at Oregon Health & Science University, Portland, OR, USA. "Importantly, as well as providing long-term normalization of cortisol, continued treatment with osilodrostat for over 72 weeks led to sustained improvements in clinical signs and physical manifestations of hypercortisolism and was generally well tolerated." "These data support Isturisa as a viable long-term medical therapy option to maintain control of cortisol levels and signs and symptoms related to hypercortisolism in patients with Cushing's disease, building on the core phase of the positive Phase III LINC 3 study, published in The Lancet Diabetes & Endocrinology in 2020,4" said Alberto M. Pedroncelli, Clinical Development & Medical Affairs Head, Global Endocrinology, Recordati AG. "Recordati Rare Diseases is committed to improving the lives of patients with this rare, debilitating and life-threatening condition. On behalf of Recordati Rare Diseases, I would like to extend our thanks to all those who have contributed to LINC 3 and the LINC clinical development program." The full publication can be found here. Important safety information for ISTURISA Indications and usage ISTURISA (osilodrostat) is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative. Warnings and precautions Hypocortisolism: ISTURISA lowers cortisol levels and can lead to hypocortisolism and sometimes life-threatening adrenal insufficiency. Lowering of cortisol can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, and dizziness. Significant lowering of serum cortisol may result in hypotension, abnormal electrolyte levels, and hypoglycemia. Hypocortisolism can occur at any time during ISTURISA treatment. Evaluate patients for precipitating causes of hypocortisolism (infection, physical stress, etc). Monitor 24-hour urinary free cortisol, serum or plasma cortisol, and patient's signs and symptoms periodically during ISTURISA treatment. Decrease or temporarily discontinue ISTURISA if urinary free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report symptoms of hypocortisolism. Stop ISTURISA and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency. After ISTURISA discontinuation, cortisol suppression may persist beyond the 4-hour half-life of ISTURISA. Please see section 5.1 of full Prescribing Information. Educate patients on the symptoms associated with hypocortisolism and advise them to contact a healthcare provider if they occur. QTc prolongation: ISTURISA is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. Perform an ECG to obtain a baseline QTc interval measurement prior to initiating therapy with ISTURISA and monitor for an effect on the QTc interval thereafter. Correct hypokalemia and/or hypomagnesemia prior to ISTURISA initiation and monitor periodically during treatment with ISTURISA. Use with caution in patients with risk factors for QT prolongation and consider more frequent ECG monitoring. Please see section 5.2 of full Prescribing Information. Elevations in adrenal hormone precursors and androgens: ISTURISA blocks cortisol synthesis and may increase circulating levels of cortisol and aldosterone precursors and androgens. This may activate mineralocorticoid receptors and cause hypokalemia, edema and hypertension. Hypokalemia should be corrected prior to initiating ISTURISA. Monitor patients treated with ISTURISA for hypokalemia, worsening of hypertension and edema. Inform patients of the symptoms associated with hyperandrogenism and advise them to contact a healthcare provider if they occur. Please see section 5.3 of full Prescribing Information. Adverse reactions Most common adverse reactions (incidence >20%) are adrenal insufficiency, fatigue, nausea, headache, and edema. To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or . Drug interactions CYP3A4 inhibitor: Reduce the dose of ISTURISA by half with concomitant use of a strong CYP3A4 inhibitor. CYP3A4 and CYP2B6 inducers: An increase of ISTURISA dosage may be needed if ISTURISA is used concomitantly with strong CYP3A4 and CYP2B6 inducers. A reduction in ISTURISA dosage may be needed if strong CYP3A4 and CYP2B6 inducers are discontinued while using ISTURISA. Use in specific populations Lactation: Breastfeeding is not recommended during treatment with ISTURISA and for at least 1 week after treatment. Please refer to full Prescribing Information. About Cushing's disease Cushing's disease is a form of Cushing's syndrome, in which chronically elevated cortisol levels is triggered by a pituitary adenoma secreting excess adrenocorticotropic hormone (ACTH).5 It is a rare, serious and difficult-to-treat disease that affects approximately one to two patients per million per year. Prolonged exposure to elevated cortisol levels is associated with considerable morbidity, mortality and impaired QoL as a result of complications and comorbidities.6 Normalization of cortisol levels is therefore a primary objective in the treatment of Cushing's disease.7 About LINC 3 LINC 3 is a prospective, multicenter, 48-week trial with an 8-week, double-blind, randomized withdrawal phase, with optional extension phase to evaluate the safety and efficacy of ISTURISA in patients with Cushing's disease. Assessment of mUFC response rate, change in mUFC, change in cardiovascular and metabolic-related parameters, change in patient-reported outcomes, changes in physical manifestations of hypercortisolism as well as general AEs and AEs of special interest were included as secondary endpoints. LINC 3 enrolled 137 patients with persistent or recurrent Cushing's disease or those with de novo disease who were not candidates for surgery.4 About ISTURISA ISTURISA is a cortisol synthesis inhibitor that works by inhibiting 11-beta-hydroxylase, an enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland. ISTURISA is available as 1 mg, 5 mg and 10 mg film-coated tablets. Please see prescribing information for detailed recommendations for the use of this product.2 In March 2020, the FDA granted marketing authorization for ISTURISA in the United States. For more information visit . References Fleseriu M, Newell-Price J, Pivonello R et al. Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension The European Journal of Endocrinology 2022. Isturisa® US prescribing information. March 2020. Ferriere A, Tabarin A. Cushing's syndrome: Treatment and new therapeutic approaches. Best Pract Res Clin Endocrinol Metab 2020;34:101381. Pivonello R, Fleseriu M, Newell-Price J et al. Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol 2020;8:748-61. Lacroix A, Feelders RA, Stratakis CA et al. Cushing's syndrome. Lancet 2015;386:913-27. Pivonello R, Isidori AM, De Martino MC et al. Complications of Cushing's syndrome: state of the art. Lancet Diabetes Endocrinol 2016;4:611-29. Nieman LK, Biller BM, Findling JW et al. Treatment of Cushing's syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100:2807-31. About Recordati Rare Diseases Inc. Recordati Rare Diseases Inc. is a biopharmaceutical company committed to providing often-overlooked orphan therapies to the underserved rare disease communities of the United States. Recordati Rare Diseases is a part of the Recordati Group, a public international specialty pharmaceutical company committed to the research and development of new specialties with a focus on treatments for rare diseases. Recordati Rare Diseases' mission is to reduce the impact of extremely rare and devastating diseases by providing urgently needed therapies. We work side-by-side with rare disease communities to increase awareness, improve diagnosis and expand availability of treatments for people with rare diseases. The company's U.S. corporate headquarters is located in Lebanon, NJ, with global headquarter offices located in Milan, Italy. For a full list of products, please click here: Recordati website: Company contact Peter Strauss Vice President, Commercial Operations (908) 721-1559 e-mail: strauss.p@recordati.com Media contact Michele Parisi (925) 864-5028 e-mail: mparisi@forwardhealthinc.com This document contains forward-looking statements relating to future events and future operating, economic and financial results of the Recordati group. By their nature, forward-looking statements involve risk and uncertainty because they depend on the occurrence of future events and circumstances. Actual results may therefore differ materially from those forecast as a result of a variety of reasons, most of which are beyond the Recordati group's control. The information on the pharmaceutical specialties and other products of the Recordati group contained in this document is intended solely as information on the Recordati group's activities and therefore, as such, it is not intended as medical scientific indication or recommendation, nor as advertising. PP-IST-US-0291

Financial Statement

15 Jun 2022

·www.biospace.com

Recordati Rare Diseases Announces Positive Data From Phase III Linc 4, Phase III Linc 3, and Illustrate ISTURISA® Studies Presented at ENDO 2022

ISTURISA® (osilodrostat) maintained normal mean urinary free cortisol (mUFC) long-term in patients with Cushing’s disease. Adrenal hormone levels changed during early treatment with ISTURISA and stabilized during long-term treatment. Patients treated with a prolonged titration interval tended to have greater persistence with therapy. LEBANON, N.J.--(BUSINESS WIRE)-- Recordati Rare Diseases Inc. announced today that multiple positive data sets highlighting ISTURISA were presented at the annual ENDO 2022 meeting in Atlanta, Georgia. The Phase III LINC 4 study demonstrates ISTURISA maintained normal mean urinary free cortisol (mUFC) long-term in patients with Cushing’s disease, the Phase III LINC 3 study found adrenal hormone levels changed during early treatment with ISTURISA while stabilizing during long-term treatment, and the ILLUSTRATE study showed patients treated with a prolonged titration interval tended to have greater persistence with therapy. ISTURISA is a cortisol synthesis inhibitor indicated in the United States for the treatment of adult patients with Cushing’s disease. Cushing’s disease is a rare, serious illness caused by a pituitary tumor that leads to overproduction of cortisol by the adrenal glands. Excess cortisol can contribute to an increased risk of morbidity and mortality. Treatment for the condition seeks to lower cortisol levels to a normal range. According to the abstract titled, “Long-term results from the Phase III LINC 4 study: osilodrostat maintained normal mUFC in patients with Cushing’s disease, with a favorable safety profile,” ISTURISA provided long-term control of cortisol production during the LINC 4 study. Key Phase III LINC 4 Study Findings: The proportion of patients with normal mean mUFC was 68.5% (n=50/73) at week 48, 61.5% (n=40/65) at week 72 and 72.4% (n=42/58) at the end-of-treatment extension (EOT) visit. Median mUFC decreased from 2.5x the upper limit of normal (ULN) (core baseline) to 0.5xULN at weeks 48 and 72, to 0.4xULN (EOT). The most common adverse events during the entire study were decreased appetite (46.6%), arthralgia (45.2%), fatigue (39.7%), nausea (37.0%), headache (34.2%) and dizziness (30.1%). Androgens and Adrenal Hormones The abstract presented titled, “Effect of osilodrostat on androgens and adrenal hormones in patients with Cushing’s disease: Long-term findings from the Phase III, prospective LINC 3 study,” summarized the influence ISTURISA has on hormone levels and examines related side effects by analyzing data from the LINC 3 Phase III study (n=137). Patients received treatment for up to 4.7 years, with the median ISTURISA exposure being 130 weeks. According to the abstract, changes in androgen and adrenal hormone levels happened during initiation of ISTURISA treatment, and remain stable or decrease during long-term therapy. The study found no clear link to ISTURISA dose. Key Phase III LINC 3 Study Findings: Following an initial increase during the core phase, mean (SD) testosterone levels decreased towards baseline levels in females and stabilized in males during long-term treatment. Of female patients with assessments at baseline and follow up, hirsutism score improved or did not change from baseline in 63/76 patients at week 48 and 55/64 patients at week 72. Overall, few patients discontinued because of adrenal hormone precursor accumulation-related AEs (1.5%; n=2/137). Real-World Study of Dosing and Titration Finally, the abstract, “Dosing and Titration of Osilodrostat in a Real-World Cohort of US Patients with Endogenous Cushing’s Disease: Analysis of the ILLUSTRATE Study,” reports findings from a retrospective chart review study that examined the medical records of 42 patients with endogenous Cushing’s syndrome (34 with Cushing’s disease) who were prescribed ISTURISA, in order to describe how their dosage was started and managed. According to the abstract, approximately 2/3 of the 34 Cushing’s disease patients included in the analysis were started at a dose similar to clinical trial dosing. Key ILLUSTRATE Study Findings: Overall, consistent with prior research data, patients with a gradual dose up-titration (i.e., prolonged titration interval) tended to have greater persistence with therapy. Treatment persistence for those enrolled ≥ 6 months prior to study end was 95.8%, mean (SD) duration of therapy was 339.2 (106.8) days. There were no new safety findings. “The data from these studies reinforces the efficacy and safety of ISTURISA as a treatment for patients with Cushing’s disease,” said Mohamed Ladha, President and General Manager North America. “We are pleased to share these data with the endocrine community and are excited to provide patients with a much-needed step forward in the management of this rare, debilitating, and potentially life-threatening condition.” All educational content of the ENDO annual meeting is planned by its program committee, and ENDO does not endorse, promote, approve, or recommend the use of any products, devices or services. Important Safety Information for ISTURISA Indications and usage ISTURISA (osilodrostat) is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. Warnings and precautions Hypocortisolism: ISTURISA lowers cortisol levels and can lead to hypocortisolism and sometimes life-threatening adrenal insufficiency. Lowering of cortisol can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, and dizziness. Significant lowering of serum cortisol may result in hypotension, abnormal electrolyte levels, and hypoglycemia. Hypocortisolism can occur at any time during ISTURISA treatment. Evaluate patients for precipitating causes of hypocortisolism (infection, physical stress, etc). Monitor 24-hour urinary free cortisol, serum or plasma cortisol, and patient’s signs and symptoms periodically during ISTURISA treatment. Decrease or temporarily discontinue ISTURISA if urinary free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report symptoms of hypocortisolism. Stop ISTURISA and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below target range and patients have symptoms of adrenal insufficiency. After ISTURISA discontinuation, cortisol suppression may persist beyond the 4-hour half-life of ISTURISA. Please see section 5.1 of full Prescribing Information. Educate patients on the symptoms associated with hypocortisolism and advise them to contact a healthcare provider if they occur. QTc prolongation: ISTURISA is associated with a dose-dependent QT interval prolongation, which may cause cardiac arrhythmias. Perform an ECG to obtain a baseline QTc interval measurement prior to initiating therapy with ISTURISA and monitor for an effect on the QTc interval thereafter. Correct hypokalemia and/or hypomagnesemia prior to ISTURISA initiation and monitor periodically during treatment with ISTURISA. Use with caution in patients with risk factors for QT prolongation and consider more frequent ECG monitoring. Please see section 5.2 of full Prescribing Information. Elevations in adrenal hormone precursors and androgens: ISTURISA blocks cortisol synthesis and may increase circulating levels of cortisol and aldosterone precursors and androgens. This may activate mineralocorticoid receptors and cause hypokalemia, edema and hypertension. Hypokalemia should be corrected prior to initiating ISTURISA. Monitor patients treated with ISTURISA for hypokalemia, worsening of hypertension and edema. Inform patients of the symptoms associated with hyperandrogenism and advise them to contact a healthcare provider if they occur. Please see section 5.3 of full Prescribing Information. Adverse reactions Most common adverse reactions (incidence >20%) are adrenal insufficiency, fatigue, nausea, headache, and edema. To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or . Drug interactions CYP3A4 inhibitor: Reduce the dose of ISTURISA by half with concomitant use of a strong CYP3A4 inhibitor. CYP3A4 and CYP2B6 inducers: An increase of ISTURISA dosage may be needed if ISTURISA is used concomitantly with strong CYP3A4 and CYP2B6 inducers. A reduction in ISTURISA dosage may be needed if strong CYP3A4 and CYP2B6 inducers are discontinued while using ISTURISA. Use in specific populations Lactation: Breastfeeding is not recommended during treatment with ISTURISA and for at least 1 week after treatment. Please refer to full Prescribing Information. About Cushing’s disease Cushing’s disease is a form of Cushing’s syndrome, in which chronically elevated cortisol levels are triggered by a pituitary adenoma secreting excess adrenocorticotropic hormone (ACTH). It is a rare, serious and difficult-to-treat disease that affects approximately one to two patients per million per year. Prolonged exposure to elevated cortisol levels is associated with considerable morbidity, mortality and impaired QoL due to complications and comorbidities. Normalization of cortisol levels is therefore a primary objective in the treatment of Cushing’s disease. About LINC 3 LINC 3 is a prospective, multicenter, 48-week trial with an 8-week, double-blind, randomized withdrawal phase to evaluate the safety and efficacy of ISTURISA in patients with Cushing’s disease. The primary endpoint in the LINC 3 trial is the proportion of patients randomized to ISTURISA and placebo, separately, at Week 26 with a mUFC ≤ULN at the end of the 8-week randomized withdrawal period (Week 34), without a dose increase during this period. The key secondary endpoint is the proportion of enrolled patients with a mUFC ≤ULN after an initial 24 weeks of open-label treatment with ISTURISA without any dose increase after Week 12. LINC 3 involved 137 patients with persistent or recurrent Cushing's disease despite pituitary surgery or de novo patients for whom surgery was not indicated or who had refused surgery. About LINC-4 LINC-4 is a large randomized, double-blinded, multicenter, 48-week trial with an initial 12-week placebo-controlled period to evaluate the safety and efficacy of osilodrostat in patients with Cushing’s disease. The primary endpoint in the LINC-4 trial is the proportion of patients randomized to ISTURISA or placebo with a mUFC ≤ULN at the end of the 12-week placebo-controlled period. The key secondary endpoint is the proportion of patients in both arms combined with a mUFC ≤ULN after 36 weeks. LINC-4 involved 73 patients with persistent or recurrent Cushing’s disease or those with de novo disease who were not candidates for surgery. About ISTURISA ISTURISA is a cortisol synthesis inhibitor that works by inhibiting 11-beta-hydroxylase, an enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland. ISTURISA is available as 1 mg, 5 mg and 10 mg film-coated tablets. Please see prescribing information for detailed recommendations for the use of this product. In March 2020, the FDA granted marketing authorization for ISTURISA in the United States. For more information visit . About Recordati Rare Diseases Inc. Recordati Rare Diseases Inc. is a biopharmaceutical company committed to providing often-overlooked orphan therapies to the underserved rare disease communities of the United States. Recordati Rare Diseases is a part of the Recordati Group, a public international specialty pharmaceutical company committed to the research and development of new specialties with a focus on treatments for rare diseases. Recordati Rare Diseases’ mission is to reduce the impact of extremely rare and devastating diseases by providing urgently needed therapies. We work side-by-side with rare disease communities to increase awareness, improve diagnosis and expand availability of treatments for people with rare diseases. The company’s U.S. corporate headquarters is located in Lebanon, NJ, with global headquarter offices located in Milan, Italy. For a full list of products, please click here: This document contains forward-looking statements relating to future events and future operating, economic and financial results of the Recordati group. By their nature, forward-looking statements involve risk and uncertainty because they depend on the occurrence of future events and circumstances. Actual results may therefore differ materially from those forecast as a result of a variety of reasons, most of which are beyond the Recordati group’s control. The information on the pharmaceutical specialties and other products of the Recordati group contained in this document is intended solely as information on the Recordati group’s activities and therefore, as such, it is not intended as medical scientific indication or recommendation, nor as advertising.

Financial Statement

100 Deals associated with Osilodrostat Phosphate

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KEGG	Wiki	ATC	Drug Bank
D11062	Osilodrostat Phosphate	H02CA02	DB11837

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cushing Syndrome	JP	Recordati Rare Diseases, Inc.	23 Mar 2021
Pituitary ACTH Hypersecretion	US	Recordati Rare Diseases, Inc.	06 Mar 2020
Endogenous Cushing Syndrome	EU	Recordati Rare Diseases, Inc.	09 Jan 2020
Endogenous Cushing Syndrome	IS	Recordati Rare Diseases, Inc.	09 Jan 2020
Endogenous Cushing Syndrome	LI	Recordati Rare Diseases, Inc.	09 Jan 2020
Endogenous Cushing Syndrome	NO	Recordati Rare Diseases, Inc.	09 Jan 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 2	US	Novartis AG	14 Jan 2009
Hypertension	Phase 2	IS	Novartis AG	14 Jan 2009
Resistant hypertension	Phase 2	US	Novartis AG	22 Dec 2008
Resistant hypertension	Phase 2	IS	Novartis AG	22 Dec 2008
Essential Hypertension	Phase 2	US	Novartis Pharmaceuticals Corp.	11 Sep 2008
Hyperaldosteronism	Phase 2	FR	Novartis AG	01 Jun 2008
Renal Insufficiency	Phase 1	BG	Novartis Pharmaceuticals Corp.	06 Nov 2015
Renal Insufficiency	Phase 1	DE	Novartis Pharmaceuticals Corp.	06 Nov 2015
liver function failure	Phase 1	US	Novartis Pharmaceuticals Corp.	21 Apr 2015

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


LINC 3 and LINC 4 (Pubmed \| J Endocr Soc)	Phase 3	Cushing Syndrome late-night salivary cortisol \| urinary free cortisol	160	Osilodrostat (Only LNSC controlled)	hemjcxjvej(ohpcybolol) = kaqqsrnrca bwzpidaqpx (xnvauyvrdc ) View more	Positive	26 Nov 2024
NCT02180217 (LINC 3, Pubmed \| J Endocrinol Invest)	Phase 3	Pituitary ACTH Hypersecretion mean urinary free cortisol (mUFC)	137	Osilodrostat 2 mg bid	ifegbytrjw(bemtobktjx) = progressively improved from baseline irrespective of mUFC control pftdnioslp (hsibkoiruv ) View more	Positive	02 May 2024
NCT02180217 (LINC 4, Pubmed \| Front Endocrinol (Lausanne))	Phase 3	Pituitary ACTH Hypersecretion mean urinary free cortisol (mUFC) \| serum cortisol \| late-night salivary cortisol (LNSC)	60	Osilodrostat	toryiesfml(iqycnkypfb) = Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports otqvgeswqa (kpkkkvyaae ) View more	Positive	01 Jan 2023
LINC 4 (ESPE2022)	Phase 3	Cushing Syndrome	80	Osilodrostat	cmrnjfgcig(nrswahsfmt) = cdcndauwxt jjgdfsmgkr (awrgvyjjmt ) View more	Positive	15 Sep 2022
LINC 4 (ESPE2022)	Phase 3	Cushing Syndrome	80	Osilodrostat	qjlscgxxdj(jpjdlzcvvc) = ahlgeysyjh zjoshwxetp (iugufejvdb )	Positive	15 Sep 2022
NCT02697734 (LINC 4, Biospace) Manual	Phase 3	Rare Diseases	-	ISTURISA	vcqnbaohek(iqabbhtymq) = decreased appetite (46.6%), arthralgia (45.2%), fatigue (39.7%), nausea (37.0%), headache (34.2%) and dizziness (30.1%). szyqstuhlp (kobmbrenbx )	Positive	15 Jun 2022
NCT02180217 (LINC 3, Biospace) Manual	Phase 3	Pituitary ACTH Hypersecretion	137	ISTURISA	eaqlotnroc(ihrfiuvipq) = upqrieixou vbkbcjhsjv (azxbccwfsb )	Positive	15 Jun 2022
NCT00817635 (CTgov)	Phase 2	Resistant hypertension	155	LCI699 (LCI699 0.25 mg BID)	omkwvlkzgx(qxwxyyhhic) = clctpyfdgv vbbxuumrei (fmjayghxhx, zluwmrfcyl - qvdhtinmcp) View more	-	02 Jun 2021
NCT00817635 (CTgov)	Phase 2	Resistant hypertension	155	LCI699 (LCI699 1 mg QD)	omkwvlkzgx(qxwxyyhhic) = lnvcjgakdo vbbxuumrei (fmjayghxhx, qmtbvxmjqf - bipmymoded) View more	-	02 Jun 2021
NCT00817414 (CTgov)	Phase 2	Hypertension	63	LCI699 (Cohort A: LCI699 0.5 mg QD)	dpszyutyfk(mbnjlxbclr) = ljinajfkat lgsmgbafxc (oqritdopoq, leooawteco - vequxbzuyh) View more	-	02 Jun 2021
NCT00817414 (CTgov)	Phase 2	Hypertension	63	LCI699 (Cohort A: LCI699 1.0 mg QD)	dpszyutyfk(mbnjlxbclr) = olwkimilhx lgsmgbafxc (oqritdopoq, xaesnettkc - bpczslhcij) View more	-	02 Jun 2021
NCT02180217 (LINC-3, Pubmed)	Phase 3	Pituitary ACTH Hypersecretion \| Cushing Syndrome	137	Osilodrostat 10 mg	vsevaaedyz(cwikitiyyx) = xiwciimzwn zuhyxkhbvi (nogofompst ) View more	-	19 Oct 2020
NCT02697734 (LINC-4, GlobeNewswire) Manual	Phase 3	Pituitary ACTH Hypersecretion	73	osilodrostat	oftysjbyxp(ivxwrbfqyy) = lqfcmpbqxw zoeqiikzcz (yzlbozbpzv ) View more	Positive	17 Jun 2020
NCT02697734 (LINC-4, GlobeNewswire) Manual	Phase 3	Pituitary ACTH Hypersecretion	73	Placebo	oftysjbyxp(ivxwrbfqyy) = owpefqmmor zoeqiikzcz (yzlbozbpzv )	Positive	17 Jun 2020

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