Cinryze IV (C1 esterase inhibitor [human] IV) / Takeda - LARVOL DELTA

Budget Impact Analysis of Lanadelumab Versus C1 Inhibitor for Hereditary Angioedema Long Term Prophylaxis: A Brazilian Private Sector Perspective (ISPOR 2025) - "Long-term prophylaxis with Lanadelumab offers a new therapeutic option, more effective compared to currently available C1 esterase inhibitors (C1-INH). The budget impact analysis suggests that the incorporation of Lanadelumab for the prophylaxis of HAE can generate substantial savings for the Brazilian supplementary health system"

HEOR • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Cost Effectiveness Analysis of Lanadelumab vs C1 Inhibitor for Long-Term Prophylaxis of Hereditary Angioedema: A Brazilian Private Sector Perspective (ISPOR 2025) - "Lanadelumab proved to be dominant, providing a more effective and cost-saving option for the prophylaxis of HAE attacks compared to C1-INH IV"

Cost effectiveness • HEOR • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Depression • Genetic Disorders • Hereditary Angioedema • Mood Disorders • Pain • Psychiatry

Indirect treatment comparison of lanadelumab and a C1-esterase inhibitor in pediatric patients with hereditary angioedema. (PubMed, J Comp Eff Res) - P3 | " This exploratory analysis suggested a trend toward greater efficacy and fewer adverse events with lanadelumab 150 mg Q2W compared with C1-INH(IV) BIW 1000 IU and 500 IU in pediatric patients with HAE. Future studies could potentially assess larger samples over longer periods of time for the long-term preventative efficacy, safety and tolerability of lanadelumab and C1-INH(IV)."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH) (clinicaltrials.gov) - P2 | N=128 | Recruiting | Sponsor: Haaglanden Medical Centre | Not yet recruiting ➔ Recruiting | Initiation date: May 2024 ➔ Nov 2024

Enrollment open • Trial initiation date • Cardiovascular • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage

Complement Inhibition: Attacking the Overshooting Inflammation @Fter Subarachnoid Hemorrhage (CIAO@SAH) (clinicaltrials.gov) - P2 | N=128 | Not yet recruiting | Sponsor: Haaglanden Medical Centre

New P2 trial • Cardiovascular • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage

Patient-level indirect treatment comparison of lanadelumab versus pdC1-INH i.v. in hereditary angioedema patients: PATCH study. (PubMed, Allergy) - "This study contributes to current knowledge in the treatment of HAE by indicating a statistically significant reduction of HAE attacks under lanadelumab compared to pdC1-INH i.v."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Genetic Disorders • Hereditary Angioedema

Living with hereditary angioedema in Australia: Findings from a national observational study using SMS to monitor the burden of disease. (PubMed, J Allergy Clin Immunol Pract) - "This study was a first of its kind, real-world, prospective, observational study of Australian patients living with hereditary angioedema. Despite the availability of effective on-demand therapies, hereditary angioedema remains burdensome. Wider access to safe and effective prophylactic therapies is needed for patients living with hereditary angioedema."

HEOR • Journal • Observational data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

PERITRANFUSIONAL C1-INHIBITOR IN PATIENTS WITH SEVERE COMPLEMENT-MEDIATED AUTOIMMUNE HEMOLYTIC ANEMIA: AN OPEN LABEL PHASE 2 TRIAL. (EHA 2022) - "In conclusion, we found no (clinically) significant effect of C1-INH on hemolysis and systemic complement activation. This may be explained by the dosing of C1-INH, which possibly was too low to counter the severe complement-mediated AIHA and additional transfusion effects."

Clinical • P2 data • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hereditary Angioedema • Immunology • Inflammation • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • ELANE

A novel murine in vivo model for acute hereditary angioedema attacks. (PubMed, Sci Rep) - "C1INH is a key inhibitor of enzymes controlling complement activation, fibrinolysis and the contact system. We also demonstrate that an HAE therapeutic, ecallantide, can prevent HAE attacks in this model. The in vivo murine model described here can facilitate the understanding of acute HAE attacks, support drug development and ultimately contribute to improved patient care."

Journal • Preclinical • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema • Hypotension • Pain

Successful treatment with Cinryze® replacement therapy of a pregnant patient with hereditary angioedema: a case report. (PubMed, J Med Case Rep) - "In the case presented, the angioedema attacks worsened as the pregnancy progressed. The treatment with Cinryze® replacement therapy was effective and safe during pregnancy, with no adverse effects on the infant."

Clinical • Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

[VIRTUAL] C1-Esterase Inhibitor for LONG-TERM Prophylaxis in Patients with Hereditary Angioedema in Kazakhstan- An Economic Evaluation (ISPOR-EU 2020) - " The analysis compared no prophylaxis versus C1-esterase inhibitor (Cinryze) prophylaxis for prevention of attacks... The analysis suggests that the long-term prophylaxis strategy would incur considerable costs far above any conventional thresholds, as expected for an orphan drug. The results are comparable with previous assessments. Since clinical parameters were largely informed by data from one clininal trial, the model interpretability in the context of real-world long-term prophylaxis is debatable."

Clinical • HEOR • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

CIAO@TBI: Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury (clinicaltrials.gov) - P2; N=106; Not yet recruiting; Sponsor: Leiden University Medical Center

Clinical • New P2 trial • CNS Disorders • Immunology • Mood Disorders • Vascular Neurology • Glial Fibrillary Acidic Protein

C1-inhibitor in Allergic ASThma Patients (clinicaltrials.gov) - P4; N=37; Terminated; Sponsor: T. van der Poll; N=60 ➔ 37; Trial completion date: Nov 2018 ➔ Oct 2019; Recruiting ➔ Terminated; Trial primary completion date: Nov 2018 ➔ Oct 2019; Interim analysis showed no differences between groups

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Asthma • Immunology • Respiratory Diseases • F2 • IL10 • IL13 • IL4 • IL5 • IL6

Hereditary Angioedema (HAE) Real-World Prophylactic and On-demand Treatment Cost in a 15 Million Commercially Insured Population: Comparison of C-1 Inhibitor (Haegarda®) versus Lanadelumab (Takhzyro®) Treated Members (AMCP 2020) - "Background: Three products have FDA approval for prophylaxis against HAE attacks: intravenous (IV) C-1 inhibitor (C1-INH IV, Cinryze®),10/10/2008; subcutaneous (SC) C1-INH (Haegarda), 6/22/2017; and SC lanadelumab (Takhzyro®), 8/23/2018...On-demand agents were defined as CI-INHs Berinert® or Ruconest®, ecallantide (Kalbitor®), or icatibant (Firazyr®), covered by the pharmacy or medical benefit... : In this small sample of members newly starting prophylactic therapy for HAE with either SC C1-INH (Haegarda®) or lanadelumab (Takhzyro®), mean prophylactic treatment cost for 180 days was over $50,000 higher for lanadelumab. There was no difference in the percentage of members with any use of on-demand HAE agents and no significant difference in the mean cost of on-demand therapy. Although the small sample size may impact these findings, these real-world data suggest SC C1-INH may be lower cost than lanadelumab during the first 180 days..."

Clinical • Real-World Evidence • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Shire announces FDA approval for label expansion of Cinryze (C1 esterase inhibitor [human]) for prevention of attacks in pediatric hereditary angioedema patients (Shire Press Release) - “Shire…today announced that the U.S. Food and Drug Administration (FDA) has approved a label expansion for CINRYZE…to help prevent angioedema attacks in children aged 6 years and older with hereditary angioedema (HAE).”

sBLA • Genetic Disorders • Hereditary Angioedema

Shire plc : 2nd quarter results (GlobeNewswire) - “HAE product sales were up 9% driven by stocking for both CINRYZE and FIRAZYR, as well as FIRAZYR demand growth, partially offset by a decline in CINRYZE demand due to a competitor launch.”

Sales • Genetic Disorders • Hereditary Angioedema

Study of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE) (clinicaltrials.gov) - P3; N=6; Active, not recruiting; Sponsor: Shire; Recruiting ➔ Active, not recruiting; Trial primary completion date: Oct 2017 ➔ Jun 2017

Enrollment closed • Trial primary completion date • Biosimilar • Cardiovascular • Complement-mediated Rare Disorders

Pediatric hereditary angioedema: what the otolaryngologist should know. (PubMed, Curr Opin Otolaryngol Head Neck Surg) - "Pediatric HAE is a potentially life-threatening disease. Targeted biologic agents have gained acceptance in treatment of acute attacks, and their use as prophylactic agents is changing the focus of management from acute intervention to preventive management. While intubation or surgical airway management may still be necessary, early intervention or prophylaxis can decrease morbidity and improve quality of life."

Clinical • Journal

"2 vragen: - is het realistisch om te denken dat met Cinryze hetzelfde effect wordt verkregen (C1-inhibitor).? - loopt een hae patiënt extra risico ivm teveel bradikinine?" (@Heiligeboon)

Patterns of Treatment and Retreatment of Acute Attacks of Hereditary Angioedema (HAE) with Standard of Care (SOC) On-Demand Medication: Results from the APeX-2 Study (AAAAI 2020) - P3; "Of these, Firazyr® SC, Berinert® IV, Cinryze® IV, and Ruconest® IV were used first-line in 53.0%, 29.3%, 10.8%, and 6.9% of attacks, respectively. Firazyr was the most frequently used SOC on-demand medication for HAE attacks and had the highest rate of retreatment. The percentage of attacks retreated with SOC on-demand medications was lower for the daily oral 110mg and 150mg berotralstat arms than in the placebo arm, suggesting reduced attack severity on berotralstat."

CINRYZE as a Donor Pre-treatment Strategy in Kidney Recipients of KDPI>60% (clinicaltrials.gov) - P1; N=72; Not yet recruiting; Sponsor: University of Wisconsin, Madison; Trial completion date: May 2021 ➔ May 2022; Trial primary completion date: May 2020 ➔ May 2021

Clinical • Trial completion date • Trial primary completion date

C1 Esterase Inhibitor for Ace-Inhibitor Angioedema: A Case Series and Literature Review. (PubMed, J Emerg Med) - "Based on our case series, C1 esterase therapy should not be utilized routinely for ACE inhibitor-induced angioedema and is not expected to prevent intubation in severe cases."

Clinical • Journal

CINRYZE as a Donor Pre-treatment Strategy in Kidney Recipients of KDPI>60% (clinicaltrials.gov) - P1; N=72; Not yet recruiting; Sponsor: University of Wisconsin, Madison; Trial completion date: May 2020 ➔ May 2021

Clinical • Trial completion date

"Cinryze for Hereditary Angio edema - also a life changer when launched" (@jms_msn)

C1-esterase inhibitor (Cinryze) use in the treatment of pediatric hereditary angioedema. (PubMed, Immunotherapy) - "Cinryzeis a nanofiltered C1-INH, approved in Europe for the acute treatment, preprocedure prevention and routine prophylaxis of HAE attacks, and for routine prophylaxis of attacks in the USA. Of the current C1-INH preparations available, Cinryze shows particular promise in the safe and effective treatment and prophylaxis of HAE attacks in pediatric age patients."

Clinical • Journal