Pegvisomant is a recombinant, PEGylated human growth hormone analogue that acts as a selective growth hormone receptor antagonist. It is used as an active pharmaceutical ingredient for the treatment of acromegaly. Unlike growth hormone receptor agonists, pegvisomant blocks growth hormone receptor signaling and consequently reduces circulating IGF-1 levels.
Pegvisomant has CAS Number 218620-50-9 and FDA UNII N824AOU5XV. The unmodified recombinant protein contains 191 amino acid residues and has a molecular weight of approximately 21,998 Da. PEG modification increases the molecular size substantially; FDA describes predominant pegvisomant molecular-weight species of approximately 42,000, 47,000 and 52,000 Da because the product predominantly contains four to six PEG polymers per protein molecule.
Pegvisomant is produced using recombinant DNA technology in a genetically modified strain of Escherichia coli. The resulting growth-hormone analogue is subsequently subjected to PEGylation and purification to obtain the active substance. FDA identifies the principal PEG attachment sites as specific lysine and terminal residues on the recombinant protein.
Because Pegvisomant is a heterogeneous PEGylated protein rather than a conventional small molecule, its quality cannot be adequately described using only conventional tests such as HPLC assay, melting point or residue on ignition. EMA's assessment specifically describes characterization of the PEGylated protein and control of its identity, purity, potency and safety.
The active substance is evaluated using analytical procedures capable of distinguishing the recombinant protein and its PEGylated forms. EMA states that routine quality-control methods were developed and validated for identity, purity, potency and safety, with biological activity being an important quality attribute.
FDA states that biological potency is determined using a cell-proliferation bioassay. This is important for your CMS: a conventional “Assay (HPLC)” percentage should not be substituted for the biological potency specification unless the applicable manufacturer's approved specification provides such a value.
Pegvisomant is a growth hormone receptor antagonist API used in pharmaceutical products for adult patients with acromegaly. EMA confirms that Somavert contains pegvisomant as its active substance and is indicated for adults with inadequate response to surgery/radiotherapy and appropriate somatostatin-analogue treatment.
Its mechanism is based on receptor antagonism rather than suppression of growth-hormone secretion. By interfering with growth hormone receptor signaling, pegvisomant decreases production of IGF-1 and other growth-hormone-dependent proteins.
Manufacturing of Pegvisomant involves recombinant production, purification of the unpegylated protein intermediate, PEGylation and downstream purification. EMA reports that the manufacturing process has been validated and that critical upstream and downstream steps were identified and controlled.
The PEGylation step is particularly important because the final active substance is heterogeneous with respect to the number and distribution of PEG chains. Therefore, product-related heterogeneity and PEGylated species must be appropriately characterized and controlled.
Pegvisomant is a protein-based active substance and requires controlled storage conditions to maintain its structural integrity and biological activity. The final storage condition should follow the approved drug-substance specification and validated stability data.
The finished Somavert product is supplied as a sterile, white lyophilized powder requiring reconstitution before injection.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |