Ruconest (conestat alfa) / Cytobioteck, HyupJin Corp, SOBI, Megapharm, Bausch Health, Pharming Group - LARVOL DELTA

Systematic Literature Review of Recombinant C1 Esterase Inhibitor (rhC1-INH) and Other Products for the On-Demand Treatment of Hereditary Angioedema Attacks (ISPOR 2025) - "Eligible publications included phases 2, 3, and 4 randomized controlled trials (RCTs) and open-label extension (OLE) studies assessing HAE attacks in patients aged ≥12 years with the following interventions: Ruconest ® (conestat alfa), Firazyr ® (icatibant), Kalbitor ® (ecallantide), sebetralstat (KVD900), and Berinert (C1 esterase inhibitor, human). The study populations and end point definitions used in clinical trials assessing acute HAE treatments have changed over time. Key study differences included route of administration, trial setting, time of treatment, attack severity at enrollment, attack location, redosing and rescue therapy criteria, patient-reported outcome assessments, and outcome definitions. Further investigation is warranted to evaluate these differences and determine whether they affected study outcomes."

Review • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

C1 Inhibitor Registry in the Treatment of Hereditary Angioedema (HAE) Attacks (clinicaltrials.gov) - P=N/A | N=181 | Completed | Sponsor: Pharming Technologies B.V. | N=300 ➔ 181

Enrollment change • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

PAIR-TAVI: Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Acute Kidney Injury • Cardiovascular • Ischemic stroke • Renal Disease • SPP1

C1 Inhibitor Registry in the Treatment of Hereditary Angioedema (HAE) Attacks (clinicaltrials.gov) - P=N/A | N=300 | Completed | Sponsor: Pharming Technologies B.V. | Recruiting ➔ Completed

Trial completion • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Clinical Response and Corresponding Blood Transcriptome Pathways Pre- And Post-Treatment Of Hereditary Angioedema Prodromes Compared To Active Swelling Attacks. (PubMed, J Allergy Clin Immunol) - "Treatment of HAE-C1INH Type 1 patients who have a well-defined prodrome that historically results in an acute attack may be justified clinically and mechanistically. This approach would represent a paradigm shift for management of HAE on-demand treatment."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • IL10 • SERPINA1 • SPARCL1 • TNFA

Treatment of Hereditary Angioedema Prodrome with Recombinant C1-esterase Inhibitor (Ruconest) (clinicaltrials.gov) - P4 | N=5 | Completed | Sponsor: Bernstein Clinical Research Center

New P4 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Safety and Efficacy of Conestat Alfa for ACE-Induced Angioedema (clinicaltrials.gov) - P3 | N=24 | Not yet recruiting | Sponsor: University of Cincinnati

New P3 trial • Cardiovascular • Congestive Heart Failure

Recombinant human C1 inhibitor improves acute cardiac function and attenuates acute myocarditis after traumatic brain injury and hemorrhagic shock in swine (IMMUNOLOGY 2024) - "Early administration of rhC1-INH inhibited CH50 (30~60%), decreased circulating levels of cTnI (85~92%), attenuated cardiac inflammation and microscopic damages, maintained systolic blood pressure, and reduced shock index and blood lactate compared to the Injury + Placebo. Thus, rhC1-INH could emerge as a promising adjunct to damage control resuscitation that may significantly protect against THISCI in severe TH patients in prehospital settings."

Late-breaking abstract • Anesthesia • Cardiovascular • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • TNNI3

Patient Registry to Evaluate the Real-world Safety of Ruconest® (clinicaltrials.gov) - P=N/A | N=152 | Completed | Sponsor: Pharming Technologies B.V. | Unknown status ➔ Completed | N=303 ➔ 152

Enrollment change • Real-world • Real-world evidence • Trial completion • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

AKI: Prevention of Acute Kidney Injury in Patients With NSTEMI (clinicaltrials.gov) - P2 | N=29 | Terminated | Sponsor: Pharming Technologies B.V. | N=220 ➔ 29 | Trial completion date: Dec 2023 ➔ Apr 2023 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2022 ➔ Apr 2023; Lower than expected study enrolment rate. New strategic considerations.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Kidney Injury • Cardiovascular • Myocardial Infarction • Nephrology • Renal Disease

Safety of Ruconest in 2-13 Year Old Hereditary Angioedema (HAE) Patients (clinicaltrials.gov) - P2 | N=57 | Completed | Sponsor: Pharming Technologies B.V. | N=20 ➔ 57

Enrollment change • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

C1 Inhibitor Registry in the Treatment of Hereditary Angioedema (HAE) Attacks (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Pharming Technologies B.V. | Unknown status ➔ Recruiting

Enrollment open • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial. (PubMed, Front Immunol) - P2 | "Conestat alfa (ConA), a recombinant human C1 inhibitor, may prevent thromboinflammation...The study results do not support the use of ConA to prevent COVID-19 progression. https://clinicaltrials.gov, identifier NCT04414631."

Journal • P2a data • Infectious Disease • Inflammation • Novel Coronavirus Disease

Pharming Group announces presentations at International Primary Immunodeficiencies Congress and the American College of Allergy, Asthma & Immunology Annual Scientific Meeting (GlobeNewswire) - "Pharming Group N.V...announces 14 poster presentations by the Company or its collaborators regarding leniolisib and RUCONEST^® at the International Primary Immunodeficiencies Congress (IPIC) and the American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting in November."

Clinical data • Hereditary Angioedema • Immunology

"and Berinert, Ruconest, Haegarda and now oral Orladeyo do the same." (@670rv)

Biologic Pathways Involved In Hereditary Angioedema And Response To Ruconest® Treatment during prodrome and attack (AAAAI 2023) - "Significant gene and pathway levels overlap between HAE prodromes and acute attacks suggesting that treatment of an HAE prodrome may be justified for preventing progression to an acute attack."

Late-breaking abstract • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • CXCL8

PAIR-TAVI: Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Trial completion date: Jan 2024 ➔ Mar 2025 | Trial primary completion date: Jan 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Acute Kidney Injury • Cardiovascular • Ischemic stroke • Renal Disease • CST3 • LCN2

Molecular modeling of C1-inhibitor as SARS-CoV-2 target identified from the immune signatures of multiple tissues: An integrated bioinformatics study. (PubMed, Cell Biochem Funct) - "The drug-gene interaction study reported that Rhucin is strongly associated with SERPING1...The gene subset is trained with supervised machine learning models by a leave-one-out cross-validation method. Explainable artificial intelligence techniques perform the model interpretation analysis."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Benefit Package of Universal Coverage Scheme for Hereditary Angioedema (HAE) Caused By C1 Esterase Inhibitor Deficiency (C1-INH) (ISPOR-EU 2022) - "From current trials, first-line therapy such as Plasma-derived C1 inhibitor, Recombinant C1 inhibitor Conestat alfa, Icatibant, and Ecallantide showed benefits over placebo. HAE may affect the budget of Thailand if patients do not receive appropriate treatment. Thus, screening, diagnosis, and effective medication for treating acute attacks are essential measures to decrease the overall HAE-related healthcare cost. However, full economic evaluation studies of first-line therapy in Thailand are needed."

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

Identification of the common differentially expressed genes and pathogenesis between neuropathic pain and aging. (PubMed, Front Neurosci) - "Aldesleukin, Valziflocept, MGD-010, Cinryze, and Rhucin were the potential effective drugs in neuropathic pain and aging. This study identified co-DEGs, revealed molecular mechanisms, demonstrated the immune microenvironment, and predicted the possible TFs, miRNAs regulation networks and new drug targets for neuropathic pain and aging, providing novel insights into further research."

Journal • Neuralgia • Pain • CD4 • CD8 • MIR363 • NCAM1

Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19 (clinicaltrials.gov) - P2 | N=38 | Completed | Sponsor: Pharming Technologies B.V. | Recruiting ➔ Completed | N=120 ➔ 38

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP

PAIR-TAVI: Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Kidney Injury • Cardiovascular • Ischemic stroke • Renal Disease • CST3 • LCN2

"#Pharming Group en @sanofi verlengen strategische samenwerkingsovereenkomst. Pharming zal de realisatie van zijn downstream-productiefaciliteit niet langer nastreven en bespaart daarmee ongeveer $40 miljoen aan investeringskosten. https://t.co/A0wDicgcAo #Ruconest $PHAR" (@ReaubertJean)

PAIR-TAVI: Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation (clinicaltrials.gov) - P2; N=250; Not yet recruiting; Sponsor: University Hospital, Basel, Switzerland

Clinical • New P2 trial • Acute Kidney Injury • Cardiovascular • Ischemic stroke • Renal Disease • CST3 • LCN2 • MRI

Physicochemical and Biological Characterization of rhC1INH Expressed in CHO Cells. (PubMed, Pharmaceuticals (Basel)) - "The current treatment options may carry the risks of either viral infection (plasma-derived Berinert) or immune reaction (human recombinant C1INH from rabbit milk, Ruconest). Comparison of the specific activity (IC value) of the rhC1INH with human C1 esterase inhibitor from blood serum showed similar inhibitory properties. These data allow us to conclude that the novel rhC1INH molecule could become a potential therapeutic option for patients with HAE/AAE."

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