Edsivo (celiprolol) / Zevra Therap - LARVOL DELTA

Challenges in the Management of Patients with Vascular Ehlers-Danlos Syndrome: Lessons from three Clinical Cases. (PubMed, Eur J Case Rep Intern Med) - "Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder marked by extreme arterial fragility, requiring high clinical suspicion to avoid misdiagnosis and inappropriate interventions.Strict adherence to evidence-based pharmacological therapy and structured long-term follow-up are crucial, as treatment discontinuation may lead to rapid and life-threatening vascular events.Management should be centralized in expert centres with a multidisciplinary approach, where individualized and predominantly conservative strategies can optimize outcomes in this high-risk population."

Journal • Genetic Disorders • Rheumatology • COL3A1

BETA-BLOCKERS ARE ASSOCIATED WITH LOWER RISK OF PANCREATIC CANCER IN PATIENTS WITH TYPE 2 DIABETES: A POPULATION-BASED COHORT STUDY (UEGW 2025) - "Primary exposure was beta-blocker use (e.g., acebutotlol, atenolol, bisoprolol, carvedilol, celiprolol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, and sotalol)...Adjusted hazard ratios (aHRs) were derived from multivariable Cox models adjusting for 31 covariates: age, sex, smoking status, alcohol use disorder, body index mass, glycemic control (in terms of time-weighted mean HbA1c), pancreatitis, cholangitis, colectomy, Charlson's comorbidity index, metabolic and cardiovascular comorbidities, and concomitant medications (aspirin, non-steroidal anti-inflammatory drugs, statins, and other antidiabetics)... Beta-blocker use was associated with a lowered risk of PC among patients with newly diagnosed T2D, in a dose- and duration-dependent manner."

Clinical • Addiction (Opioid and Alcohol) • Diabetes • Gastrointestinal Disorder • Hepatology • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

The Impact of Celiprolol in Vascular Ehlers-Danlos Syndrome: A Systematic Review of Current Evidence. (PubMed, Med Sci (Basel)) - "Celiprolol appears to be a promising treatment for reducing vascular events in vEDS patients, potentially improving quality of life and mitigating the substantial morbidity and mortality associated with vEDS. Future research should focus on refining treatment protocols, exploring mechanisms of action, and establishing comprehensive clinical guidelines to optimize patient outcomes."

Journal • Review • Cardiovascular • Genetic Disorders • Hypotension • Rheumatology

Rapid quantification of 21 antihypertensive and diuretic drugs in plasma by UPLC-MS/MS: Application to clinical and forensic cases. (PubMed, J Pharm Biomed Anal) - "The first case describes an attempted suicide by candesartan (2558 ng/mL in plasma) combined with celiprolol (18 ng/mL) and amlodipine (161 ng/mL). The second case is a diuretic-contaminated dietary supplement poisoning with plasma concentrations of 40 ng/mL for furosemide and 36 ng/mL for hydrochlorothiazide. The authors present a simple, fast, and sensitive quantification method for the analysis of 21 antihypertensive and diuretic drugs, with concentration values reported in both living subjects and post-mortem cases to aid in the often-challenging interpretation of cardiotropic drug concentrations."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension

Significance of gut breast cancer resistance protein versus organic anion transporting polypeptide 2B1 inhibition on rosuvastatin clinical drug-drug interactions. (PubMed, Drug Metab Dispos) - "Organic anion transporting polypeptide (OATP)2B1 facilitates oral absorption of many drugs including celiprolol, fexofenadine, and rosuvastatin. Strong BCRP inhibition, with a G-value >100, translated to "positive" DDIs, whereas "OATP2B1-alone" inhibitors may lead to "negative" DDIs. For example, ronacaleret and elagolix significantly reduced rosuvastatin area under the curve due to strong OATP2B1 inhibition but weak BCRP inhibition."

Journal • Breast Cancer • Oncology • Solid Tumor • SLCO2B1

Efficacy of beta-blocker agents on clinical outcomes in patients with thoracic aortic aneurysm: A systematic review and meta-analysis of randomized controlled trials. (PubMed, Vascul Pharmacol) - "We found no evidence of benefit from β-blocker treatment for patients with TAA. More robust RCTs are needed to establish evidence-based recommendations."

Clinical data • Journal • Retrospective data • Cardiovascular • Genetic Disorders

Zevra Announces Closing of Sale of Rare Pediatric Disease Priority Review Voucher for $150 Million (GlobeNewswire) - "Zevra Therapeutics, Inc...announced the closing of the sale of its Rare Pediatric Disease Priority Review Voucher (PRV) for gross proceeds of $150 million. 'We have reached another key milestone with the closing on the sale of our PRV, which we received following the successful approval of MIPLYFFA (arimoclomol) from the U.S. Food and Drug Administration (FDA)'...'The $150 million in gross proceeds is non-dilutive capital that further enhances our financial flexibility to support our strategic priorities, which includes executing on the commercial launches of MIPLYFFA and OLPRUVA, supporting our ongoing Phase 3 trial for celiprolol, and augmenting our solid balance sheet to support future investments that are in alignment with our strategic plan'."

Financing • CNS Disorders • Metabolic Disorders

Pharmacokinetic Interactions of Fruit Juices with Antihypertensive Drugs in Humans: A Systematic Review and Meta-analyses. (PubMed, Complement Ther Med) - "Co-administration of fruit juice with antihypertensive drugs can result in an increase or decrease in drugs' bioavailability, depending on the drugs' metabolism route and involvement of transporters. Though further studies are needed to confirm clinical relevance in hypertensive patients, it is advised to avoid co-consumption of fruit juice with drugs showing significant changes in pharmacokinetic parameters to prevent subtherapeutic or supratherapeutic effects."

Journal • PK/PD data • Review

Short-term pulse pressure variability: a novel prognostic marker and therapeutic target in patients with vascular Ehlers-Danlos syndrome? Preliminary results from a pilot study. (PubMed, Hypertens Res) - "Celiprolol is a β1-adrenoceptor antagonist with partial β2 agonist activity capable of reducing rates of vascular events in this setting, though the underlying mechanisms have yet to be elucidated...Further research should evaluate whether such parameters are reliable prognostic markers and therapeutic targets in this clinical setting. ABPM ambulatory blood pressure monitoring, ARV average real variability, BP blood pressure, CV coefficient of variation, DBP diastolic blood pressure, PP pulse pressure, SBP systolic blood pressure, SD standard deviation, TRI time-rate index, vEDS vascular Ehlers-Danlos syndrome."

Biomarker • Journal • Cardiovascular • Genetic Disorders • Hypertension • Rheumatology

Efficacy of Irbesartan in Celiprolol-Treated Patients With Vascular Ehlers-Danlos Syndrome. (PubMed, Circulation) - P3 | "Compared with placebo, irbesartan reduced the risk of severe symptomatic and asymptomatic arterial events in patients with vascular Ehlers-Danlos syndrome on background celiprolol therapy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02597361."

Journal • Cardiovascular • Genetic Disorders • Hypotension

Echocardiographic Assessment in Patients with Vascular Ehlers-Danlos Syndrome: Insights from an Unexplored Field. (PubMed, High Blood Press Cardiovasc Prev) - "Our study suggests that patients with vEDS have normal cardiac mass and geometry, as well as normal systolic and diastolic function. Celiprolol therapy does not seem to significantly influence such aspects. Compared with vascular imaging, less stringent follow-up with echocardiography seems reasonable in this setting. Future studies with prospective design should confirm these aspects."

Journal • Cardiovascular • Genetic Disorders • Rheumatology

Prevention of postoperative atrial arrhythmias in major bronchopulmonary cancer surgery: Celiprolol versus Diltiazem about 30 cases (ERS 2024) - "Although prevention reduces the incidence of POA, the choice of the ideal molecule remains a challenge."

Clinical • Surgery • Anesthesia • Atrial Fibrillation • Cardiovascular • Infectious Disease • Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Medical Treatment Of Patients With Vascular Ehlers Danlos Syndrome: How Does Celiprolol Treatment Work And How Does It Help (VEITH 2024) - No abstract available

Clinical • Genetic Disorders

Current Evidence and Future Perspectives in the Medical Management of Vascular Ehlers-Danlos Syndrome: Focus on Vascular Prevention. (PubMed, J Clin Med) - "In particular, celiprolol, a β1 cardio-selective blocker with a β2-agonist vasodilator effect, has been shown to reduce rates of vascular events in patients with vEDS...Drugs targeting the extracellular matrix organization and autophagy-lysosome pathways are currently under investigation and could play a role in the future. This narrative review aims to summarize current evidence and future perspectives on vEDS medical treatment, with a specific focus on vascular prevention."

Journal • Review • Cardiovascular • Gene Therapies • Genetic Disorders • Rheumatology • COL3A1

DiSCOVER: Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in Patients With Vascular Ehlers-Danlos Syndrome (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Acer Therapeutics Inc. | Trial completion date: Nov 2025 ➔ Apr 2029 | Trial primary completion date: Oct 2025 ➔ Mar 2029

Trial completion date • Trial primary completion date • Genetic Disorders • COL3A1

Evaluation of the Clinical Drug-Drug Interaction Potential of Pritelivir on Transporters and CYP450 Enzymes Using a Cocktail Approach. (PubMed, Clin Pharmacol Drug Dev) - "In 1 trial the substrates flurbiprofen (CYP2C9), bupropion (CYP2B6), and midazolam (CYP3A4) were administered simultaneously as part of the Geneva cocktail, while the substrate celiprolol (OAPT2B1) was administered separately. In another trial, the substrates repaglinide (CYP2C8) and rosuvastatin (BCRP) were administered separately...The results of these trials indicated that pritelivir has no clinically relevant effect on the exposure of substrates for the intestinal uptake transporter OATP2B1 and the CYP enzymes 3A4, 2B6, 2C9, and 2C8, and has a weak inhibitory effect on the intestinal efflux transporter BCRP. In summary, the results suggest that pritelivir has a low drug-drug interaction potential."

Journal • Breast Cancer • Herpes Simplex • Oncology • Solid Tumor • CYP2C9 • CYP3A4 • SLCO2B1

Despite celiprolol therapy, patients with vascular Ehlers-Danlos syndrome remain at risk of vascular events: A 12-year experience in an Italian referral center. (PubMed, Vasc Med) - "Nonetheless, the risk of symptomatic vascular events remained nonnegligible. Future studies should identify reliable predictors of major adverse events and explore additional therapeutic strategies that could further lower the risk of life-threatening events in this population."

Journal • Genetic Disorders • Rheumatology

Celiprolol and sympatho-immune interface in COVID-19. (PubMed, Immunology) - No abstract available

Biomarker • Clinical • Clinical guideline • Journal • P2 data • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease

Medical Treatment Of Patients With Vascular Ehlers Danlos Syndrome: How Does Celiprolol Treatment Work And How Does It Help (VEITH 2023) - No abstract available

Clinical • Genetic Disorders

Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study. (PubMed, BMJ Open Respir Res) - P4 | "Significant DH in moderate-severe COPD subjects was no different between bisoprolol or celiprolol or versus baseline. A broad spectrum of other non-invasive cardiopulmonary and domiciliary safety outcomes was equally reassuring. Bronchoprotection with a concomitant long-acting muscarinic antagonist might be an important safety measure in this context."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Improvement in Quality of Life Following Celiprolol Hydrochloride Administration in a Patient with Vascular Ehlers-Danlos Syndrome: A Case Report. (PubMed, Ann Vasc Dis) - "Vascular Ehlers-Danlos syndrome requires specialized treatment that is scientifically proven to prevent a major vascular event. Proactive genetic diagnosis is recommended in patients suspected of having vascular Ehlers-Danlos syndrome after careful patient interview."

HEOR • Journal • Genetic Disorders • Hematological Disorders

Blockade of ß-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures. (PubMed, Int J Mol Sci) - "As β-blockers are known to have anti-tumor effects on various cancer entities, this study focuses on investigating the effect of β1-selective blockers atenolol, celiprolol, bisoprolol, metoprolol, esmolol, betaxolol, and in particular, nebivolol on UM. D-nebivolol or nebivolol combined with the β2-antagonist ICI 118.551 displayed the highest anti-tumor effects, suggesting a contribution of both β1- and β2-receptors. Thus, the present study reveals the tumor control potential of nebivolol in UM, which may offer a perspective for co-adjuvant therapy to reduce recurrence or metastasis."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CASP3 • CASP7

Vascular Involvements Are Common in the Branch Arteries of the Abdominal Aorta Rather Than in the Aorta in Vascular Ehlers-Danlos Syndrome. (PubMed, CJC Open) - "Of the 20 patients, 17 took celiprolol at final assessment...During follow-up, 3 patients died due to suspected ruptures in a branch of the celiac artery, the superior mesenteric artery, and the aorta. Our findings indicate that lesions involving the branch arteries of the abdominal aorta, rather than aorta, were the most prevalent lesion type in patients with vEDS."

Journal • Cardiovascular • Genetic Disorders • Rare Diseases

β-arrestin2 recruitment by β-adrenergic receptor agonists and antagonists (PubMed, Sheng Li Xue Bao) - "We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene...The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR...β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands."

Journal • Cardiovascular • ARRB1

DiSCOVER: Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in Patients With Vascular Ehlers-Danlos Syndrome (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Acer Therapeutics Inc. | Initiation date: Jun 2022 ➔ Nov 2022

Trial initiation date • Genetic Disorders • COL3A1