Tenecteplase: biochemical and clot lysis activity comparisons

Area of Science:

• Biochemistry
• Pharmacology
• Biotechnology

Background:

• Alteplase has been the standard fibrinolytic treatment for acute cardiovascular and cerebrovascular events.
• Tenecteplase, an optimized alteplase variant, offers improved pharmacokinetic and pharmacodynamic properties.
• Multiple tenecteplase products are available, necessitating comparative quality assessments.

Purpose of the Study:

• To compare the fibrinolytic activity and product quality of Metalyse® (originator tenecteplase) and Mingfule® (tenecteplase copy).
• To identify biochemical and functional differences between the two tenecteplase formulations.

Main Methods:

• Systematic analysis of biochemical and fibrinolytic properties using routine quality testing assays.
• Mass spectrometry and surface plasmon resonance assays to evaluate molecular characteristics.
• Host cell protein quantification and clot lysis testing after plasmin incubation.

Main Results:

• Mingfule® exhibited lower clot lysis activity and reduced two-chain tenecteplase content compared to Metalyse®.
• Significant differences were observed in glycosylation patterns (sialic acid, galactosylation, fucosylation) and charge heterogeneity.
• Mingfule® showed distinct binding affinities to clearance receptors and contained substantial host cell proteins, unlike Metalyse®.

Conclusions:

• Meaningful fibrinolytic and biochemical disparities exist between Mingfule® and Metalyse® tenecteplase.
• These differences raise concerns regarding the extrapolation of clinical study data across various tenecteplase products.
• Further research is needed to ensure therapeutic equivalence and patient safety with different tenecteplase formulations.