Givlaari (givosiran) / Ironwood Pharma, Alnylam - LARVOL DELTA

Efficacy and Safety of Givosiran in Acute Hepatic Porphyria: A Systematic Review and Meta-Analysis (ACG 2026) - "Six studies including 136 patients were analyzed. The pooled population was predominantly female (109/136, 80.1%), with reported mean or median ages of 36â47 years. Givosiran significantly reduced mean AAR (MD, -10.78; 95% CI, -18.22 to -3.34; P = 0.0045; I2 = 96.1%) and annualized hemin use (MD, -41.53; 95% CI, -57.10 to -25.95; P < 0.0001; I2 = 86%)."

Retrospective data • Review • Genetic Disorders • Hematological Disorders • Hepatology • Metabolic Disorders

Acute intermittent porphyria presenting with rhabdomyolysis and polyneuropathy with severe quadriparesis and respiratory failure: A case report. (PubMed, World J Crit Care Med) - "Our case illustrates that treatment with hemin and givosiran for longer than two years may be needed for neurological recovery after an AIP attack with severe motor polyneuropathy and multisystem involvement."

Journal • Acute Kidney Injury • CNS Disorders • Epilepsy • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Pain • Renal Disease • Respiratory Diseases

Regression of indeterminate liver lesions after givosiran therapy in acute intermittent porphyria: an unusual case (SSIEM 2026) - "Although givosiran was introduced to control porphyric activity rather than to treat liver pathology, the radiologic improvement raises the question of whether these lesions were related to AIP pathophysiology and whether givosiran contributed to their resolution. This previously unreported observation warrants further investigation into the hepatic manifestations of AIP and the potential broader effects of givosiran."

Clinical • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Heart Failure • Hematological Disorders • Hepatocellular Cancer • Hepatology • Metabolic Disorders • Nephrology • Renal Disease • Solid Tumor • AFP • HMBS

Kidney function improvement with empagliflozin in acute intermittent porphyria: a case report (SSIEM 2026) - "She was treated with human hemin and subsequently started on givosiran administered monthly. Empagliflozin may represent a promising adjunctive therapy for stabilizing renal function in patients with AIP and CKD. This case supports further investigation of SGLT2 inhibitors in rare metabolic diseases associated with kidney involvement."

Case report • Clinical • Acute Kidney Injury • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease

Patient-centered and coordinated therapy with RNA interference-based givosiran for acute hepatic porphyria: real-life experience for an ultra-rare disease from Romania. (PubMed, Blood Sci) - No abstract available

Journal • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Rare Diseases

Pancreatitis Associated With Givosiran: A Real-World Pharmacovigilance Study Based on the FAERS and EudraVigilance Databases. (PubMed, Clin Ther) - "These findings identified disproportionality signals for pancreatitis-related AEs reported with givosiran in both pharmacovigilance databases. The relatively long reported TTO suggests that pancreatitis reports were observed throughout treatment, supporting continued pharmacovigilance monitoring during givosiran therapy. Interpretation should consider the inherent limitations of spontaneous reporting systems. Further studies are warranted to determine whether a causal relationship exists."

Adverse events • Journal • Real-world evidence • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Pancreatitis

Treating a patient with ADP porphyria through suppression of both hepatic and erythroid ALA production. (PubMed, Orphanet J Rare Dis) - "Despite continuation, his chronic neurological symptoms aggravated and, in an attempt to suppress erythroid ALA production, weekly erythrocyte transfusions combined with hydroxyurea was started...Years later we could trial givosiran, an ALAS1-siRNA to suppress the hepatic ALA production...This case report illustrates that ADP can be treated successfully with both hepatic and erythroid suppression. It also illustrates the challenges of treating a patient with a rare, complex and poorly understood disease, and the difficulty to balance the complications, side effects and the benefits of treatments."

Journal • Developmental Disorders • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Nephrology • Pain • Renal Disease

Advanced Management of Acute Intermittent Porphyria: The Role of Givosiran Therapy in Improving Long-Term Outcomes-A Case Study. (PubMed, Clin Case Rep) - "We report a case progressing to tetraplegia and respiratory failure with delayed diagnosis. Treatment with hemin and givosiran resulted in prevention of attacks and functional recovery, highlighting the importance of early diagnosis and long-term therapy."

Journal • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Rare Diseases • Respiratory Diseases

Biochemically Evolving Acute Hepatic Porphyria With Postpartum Progression to Severe Recurrent Neurovisceral Disease. (PubMed, Cureus) - "The patient was transitioned to givosiran after developing recurrent hemin-dependent attacks with progressive neurological and autonomic involvement. This case highlights the evolving biochemical nature of AHP, the diagnostic pitfalls, the limitations of isolated laboratory interpretation, the importance of correct sampling timing, the diagnostic significance of mechanism-directed therapeutic response, the critical role of longitudinal phenotype-driven clinical reasoning in rare metabolic disease, and the transformative role of targeted therapy."

Journal • Anorexia • Fatigue • Genetic Disorders • Hematological Disorders • Hepatology • Metabolic Disorders • Movement Disorders • Pain

Acute intermittent porphyria: When diagnostic errance jeopardizes patient health (PubMed, Rev Med Interne) - "It is essential to be aware of the epidemiology, risk factors, and suggestive symptoms of this potentially serious treatable disease to reduce diagnostic uncertainty, limit long-term complications, and improve prognosis."

Journal • Back Pain • CNS Disorders • Epilepsy • Genetic Disorders • Hematological Disorders • Hypotension • Lumbar Back Pain • Metabolic Disorders • Musculoskeletal Pain • Pain • Psychiatry

Adverse events of givosiran in the treatment of acute hepatic porphyria: a pharmacovigilance study using the FAERS and VigiAccess databases. (PubMed, Orphanet J Rare Dis) - "This study corroborates the known risks of givosiran, including elevated blood homocysteine and renal impairment, using both the FAERS and VigiAccess databases, and identifies significant associations of givosiran with pancreatitis and seizures. The consistent detection of these signals across two independent databases further supports their credibility. The random failure-type risk pattern indicates that continuous safety monitoring should be maintained throughout the entire treatment course."

Adverse events • Journal • CNS Disorders • Epilepsy • Genetic Disorders • Hematological Disorders • Mental Retardation • Metabolic Disorders • Pain • Pancreatitis • Psychiatry • Renal Disease

A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics. (PubMed, Mol Ther Nucleic Acids) - "This platform integrates preclinical and clinical data from all seven FDA-approved GalNAc-siRNA drugs-fitusiran, givosiran, inclisiran, lumasiran, vutrisiran, nedosiran, and plozasiran-spanning multiple species (mouse, rat, monkey, and human). The platform successfully predicted the PK and simulated the PD profiles of SAL0132 in humans, which demonstrated model-informed strategies to support efficient drug development of this modality. In conclusion, this platform enables users to predict GalNAc-siRNA PK/PD profiles across species by inputting specific model parameters, providing a powerful resource to guide the development of next-generation GalNAc-siRNA therapeutics."

Journal

Clinical Characteristics and Outcomes of Acute Intermittent Porphyria: Insights From the European Porphyria Registry. (PubMed, Liver Int) - "In this multicentre European study, we describe disease burden across all clinical AIP states including non-givosiran treated recurrent patients and identify risk factors associated with hospitalization and recurrent disease."

Journal • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Hypertension • Liver Cancer • Metabolic Disorders • Nephrology • Oncology • Rare Diseases • Renal Disease • Solid Tumor

Real-World Experience With Givosiran in Acute Porphyrias: A Narrative Review and a Novel Hypothesis. (PubMed, Cureus) - "Moreover, many patients suffer from breakthrough attacks, which remain a conundrum. Since gallbladder epithelial cells also contain the asialoglycoprotein receptor, which is a prerequisite for the uptake of givosiran, it could be that the siRNA-induced depletion of haem leads to a disturbance of the function of the gallbladder. Therefore, we hypothesize a potential role of the gallbladder and the metabolism of bile acids in the development of porphyria and givosiran-resistant attacks, which has to be supported by clinical or experimental validation."

Journal • Real-world evidence • Review • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Pancreatitis • ASGR

Enrollment Characteristics and Real-World Insights Into Disease Burden and Givosiran Treatment in Patients With Acute Hepatic Porphyria in the ELEVATE Registry (THSNA 2026) - P | "Enrollment results from patients in the ongoing ELEVATE registry provide insights into patient characteristics and treatment patterns. These results and continued data collection will inform subsequent analyses of the long-term safety and effectiveness of givosiran. These data also underscore the heterogeneous nature of AHP and the substantial burden of comorbidities among affected patients."

Clinical • Real-world • Real-world evidence • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Depression • Genetic Disorders • Hematological Disorders • Hepatology • Hypertension • Metabolic Disorders • Mood Disorders • Nephrology • Renal Disease

Advances in siRNA-Loaded Nanocarriers: Harnessing Cutting-Edge Technologies for Precision Cancer Treatment. (PubMed, Curr Pharm Des) - "siRNA-based therapeutics represent a promising strategy for targeted cancer therapy due to their high specificity and ability to reduce off-target toxicity. Nanocarrier systems have greatly enhanced their clinical viability. However, continued efforts are required to overcome biological barriers and facilitate clinical translation. This review also summarizes FDA-approved siRNA-based drugs such as Onpattro®, Leqvio®, Givlaari®, Oxlumo®, Tavnelis®, and Amvuttra®, underscoring the clinical potential of RNAi-based therapies."

Journal • Oncology

Biallelic pathogenic hydroxymethylbilane synthase gene variants of a neurodegenerative disorder with progressive cystic leukoencephalopathy: a case report. (PubMed, J Med Case Rep) - "For differential diagnosis of cystic leukoencephalopathy, biallelic pathogenic hydroxymethylbilane synthase gene variants should be considered. Its pathogenesis probably differentiates from acute intermittent porphyria. To date, there is no promising therapeutic approach."

Journal • CNS Disorders • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Pain • Psychiatry • Transplantation

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

Reproductive health across the lifespan in acute hepatic porphyria (ASH 2025) - "During the 5 years prior to survey completion, 51 patients received heminand 44 received givosiran (an RNAi that suppresses hepatic ALAS-1)... In this US nationwide study of 100 female patients with AHP, we characterized therelationships between reproductive health factors and disease burden. Use of cOCPs, POPs, and depotmedroxyprogesterone was associated with worsening of AHP symptoms, while LNG and copper IUDsappeared to be better tolerated. Pregnancy and lactation generally did not exacerbate symptoms of AHP,whereas perimenopause was associated with symptom worsening."

Cardiovascular • Genetic Disorders • Gynecology • Hematological Disorders • Hepatology • Hypertension • Long-acting Reversible Contraceptives • Metabolic Disorders

Class-Specific Adverse Events of Patients Treated with Small Interfering RNA Therapeutics: A Disproportionality Analysis of the United States Food and Drug Administration Adverse Event Reporting System Database Based on the MY FAERS Platform. (PubMed, Nucleic Acid Ther) - "This study aimed to identify and quantify CAE-siRNA associated with U.S. Food and Drug Administration (FDA)-approved siRNA drugs (patisiran, givosiran, vutrisiran, inclisiran, and lumasiran) using real-world pharmacovigilance data, focusing on potential class-wide effects. This study identified clinically relevant CAE-siRNA, particularly hepatic toxicity for inclisiran, supporting enhanced monitoring. While disproportionality analyses are hypothesis generating, these findings underscore the need for targeted pharmacovigilance to optimize the safety of this promising drug class."

Adverse events • Journal • Back Pain • Fatigue • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Pain • Pain

Acute hepatic porphyrias. (PubMed, Porto Biomed J) - "Treatment involves high-glucose diets, intravenous hemin for acute attacks, and givosiran for the prophylaxis of frequent attacks...AHP continues to be an underrecognized condition, warranting consideration in individuals experiencing unexplained abdominal pain, neuropathy, psychiatric symptoms, or skin lesions. There is a need for improved diagnostic techniques and treatment options."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Hematological Disorders • Hepatocellular Cancer • Hypertension • Metabolic Disorders • Nephrology • Neuralgia • Oncology • Pain • Psychiatry • Pulmonary Arterial Hypertension • Renal Disease • Solid Tumor • Transplantation

Rare Report of Simultaneous Liver and Kidney Transplant for Acute Intermittent Porphyria (KIDNEY WEEK 2025) - "At the time of transplant, she received simulect induction and was discharged on tacrolimus, cellcept, and prednisone...She has been able to stop givosiran and has had no porphyric attacks since SLKT. Discussion This case details a rare, successful SLKT for AIP, leading to complete remission of porphyric symptoms and full recovery of kidney function. AIP is among a group of select disorders where combined transplant should be considered for optimal outcomes."

Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Hepatology • Metabolic Disorders • Nephrology • Transplantation • HMBS

Integrating New Therapies into the Management of Classical Heme Disorders (ASH 2024) - "His presentation will overview the current evidence base for luspatercept as a novel disease-modifying agent targeting ineffective erythropoiesis in β-thalassemia. For Dr. Dickey's presentation, she will review the givosiran clinical trial data and the available clinical literature on givosiran, as well as highlight important unanswered questions."

Anemia • Beta-Thalassemia • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease

Givosiran: A Targeted Treatment for Acute Intermittent Porphyria (ASH 2024) - No abstract available

Genetic Disorders • Hematological Disorders • Metabolic Disorders

Neurovisceral Syndrome in a Patient with Monoclonal Gammopathy of Undetermined Significance: A Confirmed Case of Variegate Porphyria. (PubMed, Cureus) - "He was transitioned to Givosiran, resulting in symptom control and no further flares. This case reinforces the need to consider rare metabolic disorders in unexplained multisystem presentations and highlights the role of enzyme-targeting therapy when conventional treatment is not tolerated."

Journal • Alzheimer's Disease • Cognitive Disorders • Contact Dermatitis • Depression • Dermatitis • Dermatology • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Metabolic Disorders • Monoclonal Gammopathy • Pain • Psychiatry • Rare Diseases