Prospective, Single-Arm, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment-Naïve Pediatric and Adult Participants With Atypical Hemolytic Uremic Syndrome (aHUS) in China

This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety of eculizumab in participants with atypical hemolytic uremic syndrome (aHUS) in China

Start Date14 Jul 2023

Sponsor / Collaborator

Alexion Pharmaceuticals, Inc.

[+1]

NCT05886244 / Active, not recruitingPhase 3

Open-Label, Multicenter Study to Assess the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) in China

This is a Phase 3b, single-arm, open-label, multicenter study to evaluate the efficacy, safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of eculizumab in adult participants with paraxysmal noturnal hemoglobinuria (PNH) in China.

Start Date05 Jul 2023

Sponsor / Collaborator

Alexion Pharmaceuticals, Inc.

[+1]

NCT05131204 / TerminatedPhase 3

A Randomized, Open-Label, Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Currently Treated With Eculizumab or Ravulizumab

The primary objective of the study is:
To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy
The secondary objectives of the study are to:
* Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following:
* Transfusion requirements and transfusion parameters
* Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50
* Hemoglobin levels
* Fatigue as assessed by Clinical Outcome Assessments (COAs)
* Health-related quality of life (HRQoL) as assessed by COAs
* Safety and tolerability
* To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma
* To assess the immunogenicity of pozelimab and cemdisiran

Start Date06 Oct 2022

Sponsor / Collaborator

Regeneron Pharmaceuticals, Inc.

100 Clinical Results associated with Eculizumab-AAGH

100 Translational Medicine associated with Eculizumab-AAGH

100 Patents (Medical) associated with Eculizumab-AAGH

Literatures (Medical) associated with Eculizumab-AAGH

01 Sep 2024·EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab

Article

Author: Jang, Hyerin ; Lee, So Jin ; Kim, Jungryul ; Lee, Hyuna ; Park, Jihye

Abstract:

Purpose:

To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships.

Methods:

The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA).

Results:

The two-compartment model adequately described the PK of SB12 and ECU, and the subject’s weight was chosen as a clinically significant covariate affecting drugs’ clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients.

Conclusion:

The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.

01 Dec 2023·Drugs in R&D

In-Use Stability of SB12 (Eculizumab, Soliris Biosimilar) Diluted in Saline and Dextrose Infusion Solution after an Extended Storage Period

Article

Author: Lee, Yoonsook ; Kim, Soyeon ; Tak, Minji ; Kim, Jihyun ; Jeong, Hawon ; Park, Su Jin ; Yun, Jihoon

INTRODUCTION:

SB12 is a biosimilar to eculizumab reference product [Soliris^TM (Soliris is a trademark of Alexion Pharmaceuticals, Inc.)] that acts as a C5 complement protein inhibitor. The infusion stability of in-use (diluted) SB12 outside the conditions stated in the reference product's label is unknown.

OBJECTIVE:

The objective of this study was to assess the stability of SB12 after extended storage in conditions not claimed in the originator label.

METHODS:

Infusion stability was assessed in SB12 samples (diluted in 0.9% NaCl, 0.45% NaCl, and 5% dextrose, final concentration of 5 mg/mL per clinical trial protocol and the reference product's label) kept at 5 ± 3 °C for up to 3 months, then 30 ± 2 °C/65 ± 5% relative humidity (RH) for 72 h. The product was stored in different containers [polyolefin (PO) bags, glass bottles and syringes], and the protocol followed International Conference on Harmonisation (ICH) and European Medicines Agency (EMA) requirements for stability evaluation of biological products. Stability was evaluated using complementary assays, including pH, protein concentration (A₂₈₀), purity (size exclusion-high-performance liquid chromatography, capillary electrophoresis-sodium dodecyl sulfate, and imaged capillary isoelectric focusing), biological activity (C5 binding and inhibition), and safety (subvisible particles).

RESULTS:

Except for charge variants in SB12 diluted in 5% dextrose, all results met the stability acceptance criteria. There were no major changes in terms of physicochemical stability, biological activity, and subvisible particles.

CONCLUSIONS:

The infusion stability of SB12 after extended storage (5 ± 3 °C for up to 3 months, then 30 ± 2 °C/65 ± 5% RH for 72 h) was demonstrated for longer periods and at higher temperatures than what is stated in the EU and US labels of the reference product. The physicochemical properties, biological activity, and subvisible particles of in-use SB12 diluted in 0.9% NaCl and 0.45% NaCl were maintained under the described conditions and for all tested containers. However, instability was observed for the diluted SB12 in 5% dextrose. These results may reduce the workload of clinical staff and minimize drug waste from treatment delays without any loss in product quality and biological activity.

01 Jul 2023·BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy

Characterization for the Similarity Assessment between Proposed Biosimilar SB12 and Eculizumab Reference Product Using a State-of-the-Art Analytical Method.

Article

Author: Kim, Yikwon ; Lee, Jungmin ; Cho, Miju ; Hong, Eunkyoung ; Yoo, Taekyung ; Kim, Hyunsoo ; Kim, Jihye ; Hong, Seokku

BACKGROUND:

SB12 is being developed as a proposed biosimilar to eculizumab reference product (RP), a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 complement protein. Binding to this protein inhibits complement-mediated intravascular hemolysis by blocking its cleavage into C5a and C5b. Eculizumab RP is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy, generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive, and neuromyelitis optica spectrum disorder in adult patients who are anti-aquaporin-4 antibody-positive.

OBJECTIVE:

The objective of this study was to demonstrate structural, physicochemical, and biological similarity between eculizumab RP and SB12 using various state-of-the-art analytical methods.

METHODS:

Comprehensive analytical characterization was conducted with side-by-side comparison of SB12 with European Union (EU) and United States (US) eculizumab RPs using various analytical methods (more than 40 state-of-the-art assays). Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher-order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities.

RESULTS:

Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB12 is highly similar to the EU and US eculizumab RP. In the structural aspects, it was confirmed that there is no difference between post-translational modification profiles and higher-order structures of SB12 compared with the eculizumab RP. Product-related impurities in the form of aggregates and charge variants were also confirmed to be similar. Mechanism of action (MoA)-related biological activities showed that SB12 is highly similar to the EU and US eculizumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity of comparative binding tendency of SB12 and eculizumab RP to Fc gamma receptors and C1q was confirmed through additional characterization methods. Based on these results, SB12 is expected to have highly similar safety and efficacy compared with eculizumab RP.

CONCLUSION:

In summary, the overall analytical characterization and similarity assessment results show that SB12 is highly similar to the EU and US eculizumab RP in terms of structural, physicochemical, biophysical, and biological attributes.

News (Medical) associated with Eculizumab-AAGH

23 Sep 2024

·www.globenewswire.com

Samsung Bioepis Presents Totality-of-the-Evidence Supporting Extrapolation of EPYSQLI™ (SB12; Eculizumab)’s Indication, at the European Society of Paediatric Nephrology (ESPN) 2024

Sept. 23, 2024 -- Samsung Bioepis Co., Ltd. today presented the “totality-of-the-evidence” supporting extrapolation of atypical hemolytic uremic syndrome (aHUS) indication on EPYSQLI™ (SB12), a biosimilar to Soliris1 (eculizumab), at the 56th European Society for Paediatric Nephrology (ESPN 2024). The congress will be taking place from September 24 to 27, 2024 in Valencia, Spain. SB12, a biosimilar to reference eculizumab (ECU-RP), was approved by the European Commission (EC) in May 2023 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) based on the totality-of-the-evidence including analytical, non-clinical, and clinical data in healthy subjects and PNH patients2. In March 2024, EC adopted an additional indication of atypical hemolytic uremic syndrome (aHUS) for SB12 based on the principle of extrapolation, also supported by the totality-of-the-evidence. The totality-of-the-evidence presented at the ESPN 2024 compares SB12 to ECU-RP through an extensive analytical (more than 40 state-of-the-art assays) and non-clinical assessments. Clinical studies were taken to compare its pharmacokinetics (PK), pharmacodynamics (PD), efficacy, safety, tolerability, and immunogenicity in healthy subjects (Phase 1) and in complement inhibitor-naïve PNH patients. The structural, physicochemical, and biological characterization results demonstrated that SB12 is highly similar to ECU-RP. Through this evidence, the EC has adopted SB12’s usage in aHUS by principle of extrapolation. “By demonstrating biosimilarity of SB12 to reference eculizumab through robust analytical, non-clinical and clinical data, we were able to justify totality-of-the-evidence supporting extrapolation of PNH data to aHUS indication. We are excited to be sharing this data at ESPN 2024 as it represents a significant milestone in our journey to provide quality-proven therapeutic options for patients with a serious and rare disease like aHUS,” said Hyejin Kim, Vice President and Medical & Lifecycle Safety Team Leader at Samsung Bioepis. “We will continue our educational efforts to help physicians understand the principle of extrapolation, since it is an important scientific concept in biosimilar development, allowing cost-effective development and timely access to safe and effective therapies to people who need it the most.” Details of the SB12 abstract are as follows: Abstract title: Totality of the evidence supports extrapolation of atypical hemolytic uremic syndrome (aHUS) indication for EPYSQLI™ (biosimilar to reference eculizumab) Abstract number: P2.077 Authors: David Kavanagh, Eleni Gavriilaki, Jihyun Han, Jake Yongkwon Lee, Hyejin Kim, Paola Russo Besides approval by the EC, SB12 is also approved by the U.S. Food and Drug Administration (FDA) and Korea’s Ministry of Food and Drug Safety (MFDS) as a biosimilar to Soliris for the treatment of patients with PNH and aHUS. In countries where SB12 is approved and available, SB12 may not be prescribed and/or dispensed for other indications for which Soliris is approved. EPYSQLI is indicated in adults and children for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). EPYSQLI is not approved for and should not be used for the treatment of generalised myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). EPYSQLI must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with hematological disorders or renal disorders. Established in 2012, Samsung Bioepis is a biopharmaceutical company committed to realizing healthcare that is accessible to everyone. Through innovations in product development and a firm commitment to quality, Samsung Bioepis aims to become the world's leading biopharmaceutical company. Samsung Bioepis continues to advance a broad pipeline of biosimilar candidates that cover a spectrum of therapeutic areas, including immunology, oncology, ophthalmology, endocrinology, hematology and nephrology. For more information, please visit: www.samsungbioepis.com and follow us on social media – follow us on social media – X, LinkedIn. References: 1 Soliris is a trademark of Alexion Pharmaceuticals 2 European Medicines Agency. Epysqli Product Information. https://www.ema.europa.eu/en/medicines/human/EPAR/epysqli Accessed September 2024 The content above comes from the network. if any infringement, please contact us to modify.

Drug ApprovalVaccineClinical Result

25 Jul 2024

·www.pharmaceutical-technology.com

MHRA approves Pfizer-BioNTech’s Comirnaty JN.1 vaccine

The vaccine is claimed to stimulate the immune system to produce antibodies and blood cells against Covid-19. Credit: Ralf Liebhold / Shutterstock. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has authorised the use of Pfizer-BioNTech’s adapted Comirnaty vaccine to combat the JN.1 Covid-19 subvariant. The vaccine stimulates the immune system to produce antibodies and blood cells against Covid-19. This approval encompasses four variations of the Comirnaty JN.1 vaccine, following the International Recognition Procedure (IRP). The IRP, initiated in January 2024, expedites new medicine assessments by incorporating decisions from trusted regulatory partners, including the European Medicines Agency (EMA). The four Comirnaty JN.1 vaccine products authorised are intended for age groups from infants to adults. See Also: MHRA approves Novo Nordisk’s semaglutide to cut cardiovascular risk FDA approves Samsung Bioepis’ EPYSQLI as Soliris biosimilar The Comirnaty JN.1 injectable dispersion of 30 microgrammes per dosage and the Comirnaty JN.1 30 micrograms/dose dispersion for injection in a pre-filled syringe are both indicated for use in adults. A single dosage vial of Comirnaty JN.1 10 micrograms/dose dispersion for injection is intended for children aged five to 11 years. A three-dose vial of Comirnaty JN.1 3 micrograms/dose concentrate for dispersion for injection is intended for usage in infants and children aged six months to four years. These products are extensions of the existing Comirnaty 30micrograms/dose concentrate for injection. The UK regulator will carry out continuous monitoring of the vaccine’s safety. Detailed information on side effects is available in the patient information leaflet and on the MHRA website. Patients are encouraged to report any side effects through the Yellow Card scheme, which could contribute to the vaccine’s safety data. The latest development comes after the UK MHRA approved a new indication of Novo Nordisk ’s semaglutide, marketed as Wegovy, to lower the risk of serious heart problems in overweight or obese adults.

Drug ApprovalVaccine

24 Jul 2024

·www.fiercepharma.com

Surge in sales of biosimilars helps Samsung Biologics to a record-setting quarter

For the first time, Samsung Biologics has topped the 1 trillion South Korean won mark in sales for a quarter. Revenue was up 37% year over year owning largely to the success of its biosimilars unit, Samsung Bioepis. Korean CDMO juggernaut Samsung Biologics continued its sales surge in the second quarter, with its biosimilars subsidiary, Samsung Bioepis, doing much of the heavy lifting. For the period, Samsung Bioepis achieved (PDF) sales of 530 South Korean won ($384 million), which was a 107% year-over-year increase and a 75% sequential boost. The company does not specify individual sales of its biosimilars but its portfolio is loaded with copycat versions of powerhouse drugs. In July of last year, Samsung and Organon launched Hadlima, their biosimilar version of AbbVie’s Humira, in the U.S.. Samsung Biopeis develops, manufactures and supplies Hadlima in the U.S. while Organon handles its commercialization. Expect Samsung Bioepis' roll to continue as it has earned several other recent FDA approvals. Earlier this week, Samsung gained an FDA nod for Epysqli, its biosimilar edition of AstraZeneca’s rare blood disease blockbuster Soliris. Three weeks ago, the agency signed off on Pyzchiva, Samsung's biosimilar version of Johnson & Johnson’s Stelara. In May, came an FDA nod for Opuviz, Samsung and Biogen’s copycat of Regeneron and Bayer’s Eylea. The success of the biosimilar business helped spur the parent company to another lucrative quarter as Samsung Biologics topped the 1 trillion mark in South Korean won for the first time at 1.16 trillion ($839 million). It was a 34% increase year over year and a 22% boost sequentially. The sales surge fueled a profit increase of 71% year over year and 96% sequentially to 434 billion South Korean won ($314 million). In Samsung’s earnings report, there were lots of bar graphs and line charts, all telling the same story of dramatic year-to-year growth. Forget the post-pandemic malaise that slammed the CDMO industry. Samsung had none of that. Its violet-colored bar graphs show undisturbed revenue increases—with a deeper shade of purple symbolizing the most recent and lucrative period. Samsung now counts contracts with 16 of the world’s top 20 drugmakers, the company said, which is up from 14 a year ago. That includes a $1 billion production deal with an unnamed U.S. pharma company, which extends through 2030, which was revealed in a financial disclosure earlier this month. The company attributed its continued rise to the full utilization of its three plants and CEO John Rim cited the successful ramp-up of Plant No. 4. On its sprawling campus in Incheon, Samsung also said it expects to open Plant No. 5 in April of 2025. Additionally, it is constructing an ADC production facility on the site with its launch targeted by the end of this year.

Drug Approval

100 Deals associated with Eculizumab-AAGH

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Indication	Country/Location	Organization	Date
Atypical Hemolytic Uremic Syndrome	US	Samsung Bioepis Co., Ltd.	19 Jul 2024
Hemoglobinuria, Paroxysmal	EU	Samsung Bioepis Co., Ltd.	26 May 2023
Hemoglobinuria, Paroxysmal	IS	Samsung Bioepis Co., Ltd.	26 May 2023
Hemoglobinuria, Paroxysmal	LI	Samsung Bioepis Co., Ltd.	26 May 2023
Hemoglobinuria, Paroxysmal	NO	Samsung Bioepis Co., Ltd.	26 May 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04155424 (CTgov)	Phase 2/3	Neuromyelitis Optica	5	Eculizumab	rextiztqej(dflgvzouzc) = tjtoanrqyq mwnustygtw (lfaagvevzp, qpnaugybys - gfzmyogghs) View more	-	25 Sep 2024
NCT00122330 (FDA_CDER) Manual	Phase 3	Hemoglobinuria, Paroxysmal	87	Placebo	kolnkyxzgo(aayyvbhkvm) = qoakyfuxsl ulxmmewmff (ektbtnigbm ) View more	Positive	19 Jul 2024
				Eculizumab	kolnkyxzgo(aayyvbhkvm) = vafjsxpxll ulxmmewmff (ektbtnigbm ) View more
NCT04058158 (EHA2024) Manual	Phase 3	Hemoglobinuria, Paroxysmal	50	EPYSQLI	vybodzlikn(hqxrdpbyej) = azrpwdhmwi jzxnisqoar (fbqjgvaxnw )	Similar	14 May 2024
				eculizumab	vybodzlikn(hqxrdpbyej) = dzveagsuzz jzxnisqoar (fbqjgvaxnw )
NCT04058158 (CTgov)	Phase 3	Hemoglobinuria, Paroxysmal	50	SB12 (SB12)	kquopqrybv(trigkrnkcf) = fpnivbzwbi kqvvdpbfgt (zcbvhswyvo, wqqsafjnae - xhcbbsqjkc) View more	-	26 Mar 2024
				Soliris (Soliris)	kquopqrybv(trigkrnkcf) = slecvjmrdp kqvvdpbfgt (zcbvhswyvo, qrzzedubqf - jcahnwurfr) View more
NCT04752566 (CTgov)	Phase 3	Guillain-Barre Syndrome	57	Eculizumab (Eculizumab)	eizhhfnibx(kzztvheqog) = zyidbahadv kuqjsjozcu (odgbornghk, gflczditfv - mfwkvnejod) View more	-	09 Feb 2024
				Placebo (Placebo)	eizhhfnibx(kzztvheqog) = ikbbygevdl kuqjsjozcu (odgbornghk, gxqcblqxvz - tdxvzzegtj) View more
ASH2023	Phase 3	Hemoglobinuria, Paroxysmal	50	SB12	ghakhuffoz(otbzmjctfi) = epbyjygqlm hxtkydeuob (hmsfdgyhjy, [ - 126.87, 102.83])	Positive	10 Dec 2023
NCT04725812 (CRUSH, CTgov)	Phase 2	Atypical Hemolytic Uremic Syndrome \| Hemoglobinuria, Paroxysmal \| HELLP Syndrome ... View more	2	Eculizumab	ilsdbzkyxw(qyfirnpirp) = xjxeaprdry vcflgrssxw (xyuetkmxmj, exqghanasz - tywdiprqng) View more	-	29 Nov 2023
NCT03518203 (NCT03518203, CTgov)	Phase 2	Atypical Hemolytic Uremic Syndrome \| Multiple Organ Failure	23	Eculizumab	efsebhbscd(aguaejtgxr) = nalqspqtls qxukpuwnil (oidpkwqlpe, qczantijpx - maphbukped) View more	-	21 Sep 2023
C04-002 (EMA) Manual	Not Applicable	Hemoglobinuria, Paroxysmal	-	Placebo (C04-001)	jsejjgmupd(jobdsydkdk) = The most common adverse reaction was headache, (occurred mostly in the initial phase of dosing), and the most serious adverse reaction was meningococcal sepsis. dqruostknw (uvhsotveoc )	Positive	31 May 2023
				Eculizumab (C04-001)
NCT03759366 (CTgov)	Phase 3	Myasthenia Gravis	11	Eculizumab	exaifnronp(geeluopihl) = bqpqyoiaqi lmcfmmugge (ubivxrauui, olzhjkkhtp - lmsyorhjvk) View more	-	25 Aug 2022

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