Comparative bioequivalence study of sodium zirconium cyclosilicate (SZC-9) in the forms of 5 and 10 g sachets vs brand medicine (Lokelma made by AztraZeneca)

Start Date31 Aug 2024

Sponsor / Collaborator

Tabriz University of Medical Sciences

NCT06365684 / Not yet recruitingPhase 4

Sodium Zirconium Cyclosilicate to Allow Liberal Fruit and Vegetable Intake for Patients With CKD Stage 3b and 4

Rationale: Several studies have shown that higher urinary potassium excretion (as proxy for potassium intake) is associated with better kidney outcomes, lower blood pressure and improved survival. These associations are also observed in patients with (advanced) CKD. However, application in daily practice in patients with CKD, is impaired by the risk of hyperkalemia, due to metabolic acidosis and impaired renal potassium excretion in these patients. As a consequence, patients with CKD are advised to restrict their intake of fruit and vegetables, as these healthy food components are important sources of dietary potassium. This is particularly undesirable for patients with CKD in view of the very high risk of cardiovascular disease.
Concomitant use of sodium zirconium cyclosilicate (SZC) could allow a more liberal intake of fruit and vegetables for patients with CKD, as SZC effectively treats hyperkalemia and counteracts metabolic acidosis [1]. With this strategy, the beneficial effects of potassium in fruits and vegetables on (vascular) health could also become accessible to patients with CKD.
Objective: To demonstrate that a potassium-rich diet, including the use of SZC as potential rescue treatment (in case of hyperkalemia), does not result in an unacceptable rise in plasma potassium (i.e. max rise of 0.5 mmol/L and no hyperkalemia). Study Design: Investigator initiated, single center, cross-over randomized clinical trial with non-inferiority design (14 weeks, 2 groups: regular diets vs. diet with potassium rich fruits and vegetables with sodium zirconium cyclosilicate if necessary) Study population: Outpatients ( age ≥ 18 years ) with chronic kidney disease stage IIIb/IV and use of inhibitor of the renin-angiotensin system (RASi).
Intervention: Addition of fruit- and vegetables that contain 40 mmol of potassium on top of regular diet. Addition of SZC after 1 week in case hyperkaliemia develops (serum potassium > 5,5 mmol/L). Weekly measurement of plasma potassium and dose adjustment of SZC if needed

Start Date29 Apr 2024

Sponsor / Collaborator

AstraZeneca PLC

CTIS2023-507823-52-00 / Not yet recruiting

Sodium zirconium cyclosilicate to allow liberal fruit and vegetable intake for patients with CKD stage 3b and 4 (LIBERAL study)

Start Date27 Feb 2024

Sponsor / Collaborator-

100 Clinical Results associated with Sodium Zirconium Cyclosilicate

100 Translational Medicine associated with Sodium Zirconium Cyclosilicate

100 Patents (Medical) associated with Sodium Zirconium Cyclosilicate

187

Literatures (Medical) associated with Sodium Zirconium Cyclosilicate

01 Apr 2024·Pediatric nephrology (Berlin, Germany)

Safety and efficacy of sodium zirconium cyclosilicate for the management of acute and chronic hyperkalemia in children with chronic kidney disease 4–5 and on dialysis

Article

Author: King, Lillian ; Shah, Sarit ; Cleghorn, Shelley ; Khandelwal, Priyanka ; McAlister, Louise ; Shroff, Rukshana

BACKGROUND:

Sodium zirconium cyclosilicate (SZC), an ion-exchange resin, is effective in the control of hyperkalemia in adults with chronic kidney disease (CKD); reports of use in children are limited. Prolonged therapy with SZC to relax dietary potassium restriction in CKD has not been examined.

METHODS:

We conducted a retrospective chart review of patients 6 months to 18 years of age with CKD stage 4-5 or on dialysis (5D) administered SZC for sustained hyperkalemia (potassium ≥ 5.5 mEq/L, three consecutive values). Patients received SZC (0.5-10 g per dose; age-based) either short-term (< 30 days) or long-term (> 30 days).

RESULTS:

Twenty patients with median age 10.8 (inter-quartile range 3.9, 13.4) years were treated with SZC. Short-term SZC, for 5 (3, 19) days, was associated with safe management of dialysis catheter insertions (n = 5) and access dysfunction (n = 4), and was useful during palliative care (n = 1). Serum potassium levels decreased from 6.7 (6.1, 6.9) to 4.4 (3.7, 5.2) mEq/L (P < 0.001). Long-term SZC for 5.3 (4.2, 10.1) months achieved decline in serum potassium from 6.1 (5.8, 6.4) to 4.8 (4.2, 5.4) mEq/L (P < 0.001). SZC use was associated with liberalization of diet (n = 6) and was useful in patients with poor adherence to dietary restriction (n = 3). Adverse events or edema were not observed; serum sodium and blood pressure remained stable.

CONCLUSIONS:

SZC was safe and effective for the management of acute and chronic hyperkalemia in children with CKD4-5/5D. Its use was associated with relaxation of dietary potassium restriction. Studies to examine its routine use to improve diet and nutritional status in children with CKD are required.

01 Feb 2024·ESC heart failure

The efficacy and safety of new potassium binders on renin–angiotensin–aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta‐analysis

Review

Author: Aboutaleb, Aya ; Abuelazm, Mohamed ; Amin, Ahmed Mazen ; Abdelazeem, Basel ; Amin, Mostafa Atef ; Gowaily, Ibrahim ; Badr, Amr ; Turkmani, Mustafa ; Soliman, Youssef

Abstract:

Guideline‐directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin–angiotensin–aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta‐analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed‐effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02–1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57–0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24–0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin‐converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89–1.17), P = 0.76] and serum potassium change [MD: −0.31 with 95% CI (−0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12–2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head‐to‐head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).

01 Jan 2024·European journal of internal medicine

Novel potassium binders to optimize RAASi therapy in heart failure: A systematic review and meta-analysis

Review

Author: Perrone Filardi, Pasquale ; Marzano, Federica ; Colella, Angela ; Gargiulo, Paola ; Santo, Mariafrancesca Di ; Esposito, Gennaro ; Esposito, Immacolata ; Dell'Aversana, Simona ; Basile, Christian ; Carbone, Francesca ; Chirico, Alfonsina ; Paolillo, Stefania ; Fierro, Maria Francesca ; Amato, Chiara

AIMS:

Hyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients.

METHODS AND RESULTS:

PubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4-26%), decreased hyperkalemia events by 29% (95% CI: 55-92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18-0.44) compared to placebo, maintaining a good safety profile.

CONCLUSION:

NPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels.

SYSTEMATIC REVIEW REGISTRATION:

CRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811.

News (Medical) associated with Sodium Zirconium Cyclosilicate

08 Feb 2024

·www.biospace.com

AstraZeneca Full year and Q4 2023 Financial Results

Strong growth and pipeline momentum with three new medicines approved since the third quarter CAMBRIDGE, United Kingdom--(BUSINESS WIRE)-- AstraZeneca: Revenue and EPS summary FY 2023 Q4 2023 % Change % Change $m Actual CER1 $m Actual CER - Product Sales 43,789 2 4 11,323 5 5 - Alliance Revenue2 1,428 89 89 424 69 67 - Collaboration Revenue2 594 (1 ) (1 ) 277 75 74 Total Revenue 45,811 3 6 12,024 7 8 Total Revenue ex COVID-19 45,488 13 15 12,036 16 16 Reported EPS $3.84 81 96 $0.62 7 5 Core3 EPS $7.26 9 15 $1.45 5 7 Financial performance for full year 2023 (Growth numbers at CER) Total Revenue $45,811m, up 6% despite a decline of $3,736m from COVID-19 medicines4 Excluding COVID-19 medicines, Total Revenue increased 15% and Product Sales increased 14% Double-digit Total Revenue growth from Oncology 21%, CVRM 18%, R&I 10%, and Rare Disease 12% Core Product Sales Gross Margin5 of 82%, up two percentage points, reflecting the decline in sales of lower margin COVID‑19 medicines Core Operating Margin of 32% increased by two percentage points including the previously announced gain from an update to the contractual relationships for Beyfortus, totalling $712m and recorded as Core Other operating income. In the quarter, higher SG&A expense drove lower operating margins, partly due to phasing of expenses and increased investment in launches for Airsupra, Wainua and Truqap The Core Tax Rate for the year was 17%. In the fourth quarter, the tax rate was negatively impacted by reviews by tax authorities, administrative appeal processes and other adjustments, offset by a routine intragroup reorganisation of IP, leading to a tax rate of 10% in the quarter Core EPS increased 15% to $7.26 Second interim dividend declared of $1.97 per share, making a total dividend declared for FY 2023 of $2.90 per share Total Revenue and Core EPS in FY 2024 are each expected to increase by a low double-digit to low teens percentage at CER Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "As AstraZeneca celebrates its 25th anniversary, we are pleased to report another year of strong financial performance and scientific progress, with double-digit earnings growth, and investment in exciting areas of science, including antibody drug conjugates and cell therapies, that lay the foundations for long-term success. We expect another year of strong growth in 2024, driven by continued adoption of our medicines across geographies. Our differentiated and growing portfolio of approved medicines, global reach and rich R&D pipeline give us confidence that we will continue to deliver industry-leading growth." Key milestones achieved since the prior results announcement Three first approvals for new molecular entities: Truqap (capivasertib), Wainua (eplontersen), Voydeya (danicopan) US approvals for Truqap plus Faslodex in HR-positive, HER2-negative advanced breast cancer with biomarker alterations (CAPItello-291), and Wainua for ATTRv-PN (NEURO-TTRansform). China approvals for Imfinzi in mBTC (TOPAZ-1) and Beyfortus for prevention of RSV in infants (MEDLEY/MELODY). First approval, in Japan, for Voydeya, as an add-on therapy to Ultomiris or Soliris for PNH with EVH (ALPHA) Enhertu granted Priority Review in the US for patients with metastatic HER2-positive solid tumours Guidance The Company issues its Total Revenue and Core EPS guidance for FY 2024 at CER, based on the average foreign exchange rates through 2023. Total Revenue is expected to increase by a low double-digit to low teens percentage Core EPS is expected to increase by a low double-digit to low teens percentage Collaboration Revenue is expected to increase substantially, driven by success-based milestones and certain anticipated transactions Other operating income is expected to decrease substantially (FY 2023 included a $241m gain on the disposal of Pulmicort Flexhaler US rights, and a $712m one-time gain relating to updates to contractual arrangements for Beyfortus) The Core Tax rate is expected to be between 18-22% The Company is unable to provide guidance on a Reported basis because it cannot reliably forecast material elements of the Reported results, including any fair value adjustments arising on acquisition-related liabilities, intangible asset impairment charges and legal settlement provisions. Please refer to the cautionary statements section regarding forward-looking statements at the end of this announcement. Currency impact If foreign exchange rates for February 2024 to December 2024 were to remain at the average rates seen in January 2024, it is anticipated that both FY 2024 Total Revenue and Core EPS would incur a low single-digit adverse impact versus the performance at CER. The Company's foreign exchange rate sensitivity analysis is provided in Table 19. Investor Day AstraZeneca will host an Investor Day on 21 May 2024. For more information, see . Table 1: Key elements of Total Revenue performance in Q4 2023 % Change Revenue type $m Actual % CER % Product Sales 11,323 5 5 * Excluding COVID-19 medicines, Q4 2023 Product Sales increased by 14% Alliance Revenue 424 69 67 * $281m for Enhertu (Q4 2022: $188m) * $80m for Tezspire (Q4 2022: $37m) * $41m for Beyfortus (Q4 2022: $nil) Collaboration Revenue 277 75 74 * $245m Lynparza regulatory milestone (Q4 2022: $105m) * $27m Beyfortus sales milestone (Q4 2022: $nil) Total Revenue 12,024 7 8 * Excluding COVID-19 medicines, Q4 2023 Total Revenue increased by 16% Therapy areas $m Actual % CER % Oncology 4,989 23 24 * Strong performance across all key medicines and regions CVRM 2,702 18 18 * Farxiga up 36% (35% at CER), Lokelma up 38%, roxadustat up 27%, Brilinta declined 5% (4% at CER) R&I 1,675 13 13 * Fasenra up 10% (9% CER), Breztri up 72%. Saphnelo and Tezspire also continue to grow rapidly, partially offset by a 16% decline in Symbicort following entry of a generic competitor in the US in the third quarter V&I 413 (64 ) (66 ) * $6m revenue from COVID-19 mAbs and ‑$17m for Vaxzevria, both resulting from historic contracts (Q4 2022: $734m and $95m respectively) * Beyfortus $122m, including $41m of Alliance Revenue for AstraZeneca's share of gross profits outside US, $27m of Collaboration Revenue for a sales milestone and $54m of Product Sales from product supplied to Sanofi Rare Disease 1,971 9 9 * Ultomiris up 39% (38% at CER), partially offset by decline in Soliris of 15% (13% at CER) * Strensiq up 12% (13% at CER) and Koselugo up 46% (48% at CER) reflecting strong patient demand Other Medicines 274 (33 ) (32 ) * Nexium generic competition in Japan Total Revenue 12,024 7 8 Regions inc. COVID-19 $m Actual % CER % US 5,101 7 6 Emerging Markets 2,783 2 8 - China 1,382 16 16 - Ex-China Emerging Markets 1,401 (9 ) 2 Europe 2,880 25 17 Established RoW 1,259 (9 ) (6 ) Total Revenue inc. COVID-19 12,024 7 8 * Growth rates impacted by lower sales of COVID-19 medicines (see table below) Regions ex. COVID-19 $m Actual % CER % US 5,101 12 12 Emerging Markets 2,791 15 22 - China 1,382 16 16 - Ex-China Emerging Markets 1,409 14 27 Europe 2,884 33 25 Established RoW 1,259 4 8 Total Revenue ex. COVID-19 12,036 16 16 Table 2: Key elements of financial performance in Q4 2023 Metric Reported Reported change Core Core change Comments6 Total Revenue $12,024m 7% Actual 8% CER $12,024m 7% Actual 8% CER * Excluding COVID-19 medicines, Q4 2023 Total Revenue increased by 16% * See Table 1 and the Total Revenue section of this document for further details Product Sales Gross Margin 80% +6pp Actual +6pp CER 80% +3pp Actual +2pp CER + In the prior year period, gross margins were reduced due to inventory write-downs and manufacturing contract terminations for Evusheld * Variations in Product Sales Gross Margin can be expected between periods due to product seasonality, foreign exchange fluctuations and other effects R&D expense $3,073m 17% Actual 15% CER $2,914m 15% Actual 14% CER + Increased investment in the pipeline * Core R&D-to-Total Revenue ratio of 24% (Q4 2022: 23%) + Quarterly phasing impact SG&A expense $5,371m 16% Actual 16% CER $4,034m 13% Actual 12% CER + Market development for recent launches and pre-launch activities * Core SG&A-to-Total Revenue ratio of 34% (Q4 2022: 32%) + Quarterly phasing impact Other operating income and expense7 $107m -43% Actual -42% CER $107m -17% Actual -15% CER ‒ Discontinuation of brazikumab development Operating Margin 10% +1pp Actual +1pp CER 23% Stable * See Product Sales Gross Margin, expenses and Other operating income and expense commentary above Net finance expense $337m 7% Actual 3% CER $259m 5% Actual 1% CER + Higher rates on floating debt and bond issuances + Increased Interest expense on income tax balances ‒ Higher interest received on cash and short-term investments Tax rate -7% +9pp Actual +13pp CER 10% Stable ‒ Intragroup purchase of intellectual property + Reviews by tax authorities, administrative appeals and changes to certain deferred tax balances * Variations in the tax rate can be expected between periods EPS $0.62 7% Actual 5% CER $1.45 5% Actual 7% CER * Further details of differences between Reported and Core are shown in Table 14 Table 3: Pipeline highlights since prior results announcement Event Medicine Indication / Trial Event Regulatory approvals and other regulatory actions Truqap HR-positive HER2-negative advanced breast cancer with biomarker alterations (CAPItello-291) Regulatory approval (US) Imfinzi Biliary tract cancer (TOPAZ-1) Regulatory approval (CN) Wainua ATTRv-PN (NEURO-TTRansform) Regulatory approval (US) Beyfortus RSV (MELODY-MEDLEY) Regulatory approval (CN) Voydeya PNH with EVH (ALPHA) Regulatory approval (JP) Regulatory submissions or acceptances* Lynparza gBRCA breast cancer (adjuvant) (OlympiA) Regulatory submission (CN) Lynparza + Imfinzi Endometrial cancer (1st-line) (DUO-E) Regulatory submission (US, EU, JP) Enhertu HER2-expressing tumours (DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02) Regulatory submission (US), Priority Review (US) Enhertu HER2+/HER2-low gastric (1st-line) (DESTINY-Gastric01) Regulatory submission (CN) Imfinzi + Imjudo NSCLC (neoadjuvant) (AEGEAN) Regulatory submission (EU) Wainua ATTRv-PN (NEURO-TTRansform) Regulatory submission (EU) Fasenra EGPA (MANDARA) Regulatory submission (US, EU, JP) Ultomiris NMOSD (CHAMPION-NMOSD) Regulatory submission (US) Ultomiris gMG Regulatory submission (CN) Major Phase III data readouts and other developments Imfinzi NSCLC (unresectable, Stg. III) (PACIFIC-2) Primary endpoint not met acoramidis 8 ATTR-CM Primary endpoint met *US, EU and China regulatory submission denotes filing acceptance Upcoming pipeline catalysts For a table of anticipated timings of key trial readouts, please refer to page 3 of the Clinical Trials Appendix, available on . Table 4: Phase III trials started since 1 January 2023 Medicine Trial name Indication datopotamab deruxtecan AVANZAR NSCLC (1st-line) TROPION-Lung07 Non-squamous NSCLC (1st-line) TROPION-Breast04 Neoadjuvant/adjuvant triple-negative or HR-low/HER2-negative breast cancer TROPION-Breast05 PD-L1-positive locally recurrent inoperable or metastatic TNBC camizestrant CAMBRIA-1 HR-positive/HER2-negative adjuvant breast cancer CAMBRIA-2 HR-positive/HER2-negative adjuvant breast cancer Truqap CAPItello-292 HR-positive/HER2-negative advanced breast cancer volrustomig eVOLVE-Cervical High-risk locally advanced cervical cancer eVOLVE-Lung02 mNSCLC (1st-line) with PD-L1 <50% eVOLVE-Meso Unresectable malignant pleural mesothelioma (1st-line) eVOLVE-HNSCC Unresected, locally advanced HNSCC rilvegostomig ARTEMIDE-Biliary01 BTC with curative intent saruparib EvoPAR-PR01 HRRm and Non-HRRm mCSPC zibo/dapa ZENITH High Proteinuria CKD with high proteinuria Saphnelo DAISY Systemic sclerosis baxdrostat BaxHTN Uncontrolled, including treatment-resistant, hypertension Tezspire CROSSING Eosinophilic oesophagitis Breztri LITHOS Mild to moderate asthma ATHLOS COPD pMDI portfolio HFO1234ze + Breztri COPD HFO1234ze Mucociliary clearance in healthy volunteers HFO1234ze Asthma tozorakimab MIRANDA COPD ipavibart (AZD3152) SUPERNOVA COVID-19 prophylaxis Ultomiris ARTEMIS Cardiac surgery-associated acute kidney injury ALXN2220 DepleTTR-CM Transthyretin amyloid cardiomyopathy efzimfotase alfa (ALXN1850) HICKORY Hypophosphatasia Corporate and business development In November 2023, AstraZeneca launched Evinova, with an ambition to become a leading provider of digital health solutions to better meet the needs of healthcare professionals, regulators and patients. Evinova will prioritise bringing to market established and scaled digital technology solutions already being used globally by AstraZeneca to optimise clinical trial design and delivery. Globally-leading clinical research organisations Parexel and Fortrea have entered into agreements to offer Evinova digital health solutions to their wide customer base. In December 2023, AstraZeneca entered into a definitive agreement to acquire Icosavax, Inc (Icosavax). The acquisition strengthens AstraZeneca's late-stage pipeline with Icosavax's lead investigational vaccine candidate, IVX-A12, a potential first-in-class, Phase III-ready, combination VLP vaccine that targets both RSV and hMPV. RSV and hMPV are both leading causes of severe respiratory infection and hospitalisation in adults 60 years of age and older and those with chronic conditions such as cardiovascular, renal and respiratory disease. Subject to the satisfaction of the conditions in the merger agreement, the acquisition is expected to close in the first quarter of 2024. In December 2023, AstraZeneca entered into a definitive agreement to acquire Gracell Biotechnologies Inc. (Gracell), a global clinical-stage biopharmaceutical company developing innovative cell therapies for the treatment of cancer and autoimmune diseases. The proposed acquisition will enrich AstraZeneca's growing pipeline of cell therapies with GC012F, a novel, clinical-stage FasTCAR-enabled BCMA and CD19 dual-targeting CAR-T therapy, a potential new treatment for multiple myeloma, as well as other haematologic malignancies and autoimmune diseases including systemic lupus erythematosus. The transaction is expected to close in the first quarter of 2024, subject to customary closing conditions, including regulatory clearances, and Gracell shareholder approval. In February 2024, AstraZeneca announced that it is investing $300 million in a state-of-the-art facility in Rockville, Maryland to establish life-saving cell therapy platforms for critical cancer trials and future commercial supply. To align with clinical trial timelines, the site will initially focus on pivotal clinical trial manufacturing of CAR-T cell therapies to meet current clinical supply demand. More than 150 new highly skilled jobs will be created to initially focus on manufacturing T-cell therapies to enable clinical trials to be conducted around the world. Over time, the site may expand its focus to support other therapy areas. Sustainability highlights Through the Sustainable Markets Initiative Health Systems Task Force, AstraZeneca announced an industry-first renewable power agreement in China together with four global healthcare leaders and renewable energy company Envision Energy, resulting in potential annual emissions savings of approximately 120,000 tonnes, the equivalent of taking 25,000 cars off the road. See the Sustainability section in this document for further details. Conference call A conference call and webcast for investors and analysts will begin today, 8 February 2024, at 11:45 UK time. Details can be accessed via astrazeneca.com. Reporting calendar The Company intends to publish its Q1 2024 results on 25 April 2024. To read AstraZeneca's Full Year and Q4 2023 Financial Results press release in full, click here. ______________________________ 1 Constant exchange rates. The differences between Actual Change and CER Change are due to foreign exchange movements between periods in 2023 vs. 2022. CER financial measures are not accounted for according to generally accepted accounting principles (GAAP) because they remove the effects of currency movements from Reported results. 2 Effective 1 January 2023, the Group has updated the presentation of Total Revenue. For further details of the presentation of Alliance Revenue and Collaboration Revenue, see the Basis of preparation and accounting policies section of the Notes to the Condensed consolidated financial statements section. 3 Core financial measures are adjusted to exclude certain items. The differences between Reported and Core measures are primarily due to costs relating to the acquisition of Alexion, amortisation of intangibles, impairments, legal settlements and restructuring charges. A full reconciliation between Reported EPS and Core EPS is provided in Table 13 and Table 14 in the Financial performance section of this document. 4 The COVID-19 medicines are Vaxzevria, Evusheld, and sipavibart (AZD3152) – the COVID-19 antibody currently in development. 5 The calculation of Reported and Core Product Sales Gross Margin (formerly termed as Gross Margin) excludes the impact of Alliance Revenue and Collaboration Revenue. 6 In Table 2, the plus and minus symbols denote the directional impact of the item being discussed, e.g. a ‘+’ symbol next to an R&D expense comment indicates that the item increased the R&D expense relative to the prior year. 7 Income from disposals of assets and businesses, where the Group does not retain a significant ongoing economic interest, continue to be recorded in Other operating income and expense in the Company’s financial statements. 8 Partnered with BridgeBio Pharma Inc (BridgeBio) – AstraZeneca has rights to commercialise acamoridis in Japan View source version on businesswire.com: Contacts US Media Inquiries Brendan McEvoy, +1 302 885 2677 US Media Mailbox: usmediateam@astrazeneca.com Source: AstraZeneca View this news release online at:

Drug ApprovalVaccineAcquisitionPhase 3Immunotherapy

01 Dec 2023

·www.fiercepharma.com

AstraZeneca calls it quits on pair of trials for hyperkalemia drug it scored in buyout of ZS Pharma

The move to discontinue the studies isn’t influenced by safety concerns and the positive profile of Lokelma remains intact in its hyperkalemia indication, AstraZeneca said Friday. After a hard-fought battle for FDA approval, AstraZeneca has hit another setback on its quest to turn its potassium-reduction drug Lokelma into a blockbuster. AstraZeneca has put the kibosh on two late-stage Lokelma trials testing the hyperkalemia drug in patients with heart and kidney diseases. The studies, dubbed STABILIZE-CKD and DIALIZE-Outcomes, were called off due to “substantially increased enrollment times and low event rates,” respectively, AZ said in a press release Friday. Those hurdles made it “prohibitive” for the trials to read out within the timeframe required to meaningfully advance clinical practice, AstraZeneca added. Hyperkalemia is the term for elevated levels of potassium in the blood. Patients with higher potassium levels are at risk of cardiac arrhythmias, which can lead to cardiac arrest, AZ explained. Globally, there are about 840 million patients with chronic kidney disease (CKD) and 64 million with heart failure, many of whom will develop hyperkalemia. Those patients often receive renin–angiotensin–aldosterone system inhibitor (RAASi) drugs to slow down CKD progression and reduce cardiovascular events. But the dose is often lowered or therapy is discontinued when hyperkalemia is diagnosed, leading to worse patient outcomes, AZ said. As for the trials themselves, STABILIZE-CKD was testing the effects of Lokelma and optimized RAASi therapy on CKD progression in kidney disease patients either with or at-risk of hyperkalemia. DIALIZE-Outcomes, for its part, evaluated the effects of Lokelma alone on arrhythmia-related cardiovascular outcomes in patients on chronic hemodialysis with recurrent hyperkalemia. The move to discontinue the studies isn’t influenced by safety concerns and the positive benefit-risk profile of Lokelma remains intact in its approved indication, AstraZeneca said in its release. In 2018, after several years of rejections spurred by manufacturing problems, the drug won an approval to treat hyperkalemia in adults. The drug, which formerly went by the code name ZS-9, was one of the motivations behind AstraZeneca’s $2.7 billion buyout of ZS Pharma back in 2015. At the time, the companies hoped they could turn Lokelma into a blockbuster. AZ’s hyperkalemia drug still has a long way to go before it breaks the billion-dollar threshold, however. In 2022, the medication brought home global sales of $289 million. Meanwhile, analysts at GlobalData earlier this month predicted Lokelma could generate around $799 million in 2029.

AcquisitionDrug ApprovalClinical Study

01 Dec 2023

·endpts.com

AstraZeneca halts two PhIII hyperkalemia studies intended to spotlight Lokelma’s clinical value

AstraZeneca announced early Friday morning that it is stopping work on two late-stage trials designed to gather value-added evidence for Lokelma in hyperkalemia, a chronic condition for which the drug is already approved. The Phase III STABILIZE-CKD trial faced “substantially increased enrolment timelines,” while the Phase III DIALIZE-Outcomes trial reported low event rates. As such, “ it was prohibitive to deliver study results within a timeframe to meaningfully advance clinical practice,” the company said in a press release. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Phase 3Clinical Trial Failure

100 Deals associated with Sodium Zirconium Cyclosilicate

External Link

KEGG	Wiki	ATC	Drug Bank
D10727	Sodium Zirconium Cyclosilicate	V03AE10	DB14048

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hyperkalemia	EU	AstraZeneca AB	22 Mar 2018
Hyperkalemia	IS	AstraZeneca AB	22 Mar 2018
Hyperkalemia	LI	AstraZeneca AB	22 Mar 2018
Hyperkalemia	NO	AstraZeneca AB	22 Mar 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nephrosis	Phase 3	US	AstraZeneca AB	30 Sep 2021
Nephrosis	Phase 3	US	AstraZeneca Investment (China) Co. Ltd.	30 Sep 2021
Nephrosis	Phase 3	US	AndersonBrecon, Inc.	30 Sep 2021
Nephrosis	Phase 3	JP	AstraZeneca Investment (China) Co. Ltd.	30 Sep 2021
Nephrosis	Phase 3	JP	AndersonBrecon, Inc.	30 Sep 2021
Nephrosis	Phase 3	JP	AstraZeneca AB	30 Sep 2021
Nephrosis	Phase 3	AR	AstraZeneca Investment (China) Co. Ltd.	30 Sep 2021
Nephrosis	Phase 3	AR	AndersonBrecon, Inc.	30 Sep 2021
Nephrosis	Phase 3	AR	AstraZeneca AB	30 Sep 2021
Nephrosis	Phase 3	BR	AstraZeneca AB	30 Sep 2021

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04788641 (MO199, CTgov)	Phase 1	Hyperkalemia	62	Tacrolimus (Treatment A: Tacrolimus (5 mg))	vfjgyqfamk(gmerftfeup) = yqopgjtzoh vlcooryjfc (talxrosazt, evgechvmjj - fjrifhigay) View more	-	05 Apr 2024
				SZC+Tacrolimus (Treatment B: Tacrolimus (5 mg) and SZC (15 g))	vfjgyqfamk(gmerftfeup) = xknpcbobls vlcooryjfc (talxrosazt, kflztspquk - oaghqkxyti) View more
NCT04207203 (HELPFUL trial, ERA2023)	Not Applicable	Chronic Kidney Diseases	22	Sodium Zirconium Cyclosilicate	jdgzpggobn(wtpjbsjhlp) = pufowuhhfc bleeqfnpjq (yqnjfbqtgr ) View more	-	15 Jun 2023
NCT04207203 (HELPFUL trial, ERA2023)	Not Applicable	Chronic Kidney Diseases	22	Sodium Zirconium Cyclosilicate (SZC)	jwfdhncchw(rasmnfpfgi) = kuinstwdhy wfgclysplg (ctefrhfulc ) View more	Positive	14 Jun 2023
				Sodium Zirconium Cyclosilicate	jwfdhncchw(rasmnfpfgi) = dthhijyaft wfgclysplg (ctefrhfulc ) View more
NCT04217590 (DIALIZE China, CTgov)	Phase 3	Hyperkalemia	134	Sodium Zirconium Cyclosilicate (Sodium Zirconium Cyclosilicate (SZC))	rrjfyfuzxe(xrgtugomcv) = efjynhidyk pnwthzfayl (jatemmbnaj, ysmgsnxgdb - azqsktcmki) View more	-	28 Mar 2023
				Placebo (Placebo)	rrjfyfuzxe(xrgtugomcv) = oktmxdvwnx pnwthzfayl (jatemmbnaj, gxemelpklz - keuqfytfap) View more
NCT03303521 (DIALIZE, ASN2022) Manual	Phase 3	Hyperkalemia	134	Sodium Zirconium Cyclosilicate	brlpdgcdxn(urhsgmpiqw) = atpbpdcrwi zhbbqqeeyg (gphfazjsfm ) View more	Positive	03 Nov 2022
				Placebo	brlpdgcdxn(urhsgmpiqw) = zscplkgaif zhbbqqeeyg (gphfazjsfm ) View more
NCT04217590 (DIALIZE China, ASN2022)	Phase 3	Hyperkalemia	134	Sodium Zirconium Cyclosilicate (SZC)	iktaybwowd(zevgqndtlg) = fbovdvoyye gjfbzmvqre (hecmzstazf )	Positive	03 Nov 2022
				Placebo (PBO)	iktaybwowd(zevgqndtlg) = svwggokmbl gjfbzmvqre (hecmzstazf )
NCT04207203 (MO580, ERA2022)	Not Applicable	Chronic Kidney Diseases	36	SZC	jwdkodcgzc(rwzpqbjqpy) = phxxyehsrn ensegwxbpf (vfiffjjfjg )	Positive	03 May 2022
NCT04788641 (MO199, ERA2022)	Phase 1	Hyperkalemia	31	Tacrolimus 5 mg	ekosopjcut(gwkddvhvxi) = gfueiflgni jkaquxidrk (cfkmavwuxo, 58.7 - 73.2) View more	Negative	03 May 2022
				Tacrolimus 5 mg + SZC 15 g	obpfcciwxy(roqpgtuzek) = huhiofeixp liqyqifztd (rytpyoswai )
ASN2021	Not Applicable	Heart Failure	-	Sodium Zirconium Cyclosilicate (SZC)	igbseryqfe(zqzaqllezh): HR = 1.89 (95% CI, 1.05 - 3.39) View more	Negative	27 Oct 2021
				Patiromer
NCT03532009 (CTgov)	Phase 2	Heart Failure	182	Placebo	ssgnabedga(fubhhfgonu) = xbosmdgejz xjoqfhcnsa (llvdghaxfi, whvultiokr - ehklikocma) View more	-	15 Jun 2021

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