Eptinezumab is a recombinant humanized IgG1 monoclonal antibody that specifically binds to calcitonin gene-related peptide (CGRP). It is developed for the preventive treatment of migraine in adults and is marketed as VYEPTI (eptinezumab-jjmr).
Eptinezumab is a biologic therapeutic antibody belonging to the anti-CGRP monoclonal antibody class. It binds to the CGRP ligand and prevents CGRP from interacting with its receptor, thereby inhibiting CGRP-mediated signaling associated with migraine pathophysiology.
Eptinezumab has the CAS Registry Number 1644539-04-7 and FDA UNII 8202AY8I7H. It is also known by the development names ALD403 and ALD-403.
Eptinezumab is a humanized IgG1 monoclonal antibody consisting of two heavy chains and two light chains. FDA characterization identifies two 441-amino-acid heavy chains and two 219-amino-acid light chains, with 14 intrachain and 4 interchain disulfide bonds. Its reported molecular weight is approximately 143.283 kDa.
The reported molecular formula is:
C₆₃₅₂H₉₈₃₈N₁₆₉₄O₁₉₉₂S₄₆.
Eptinezumab binds specifically to CGRP ligand and blocks its binding to the CGRP receptor. By inhibiting CGRP activity, eptinezumab helps prevent the biological signaling involved in migraine development.
Eptinezumab is used for the preventive treatment of migraine in adults, including patients with episodic and chronic migraine.
Eptinezumab is a biological drug substance, not a conventional synthetic small-molecule API. It is produced using recombinant DNA technology in Pichia pastoris yeast cells.
For pharmaceutical manufacturing, its quality assessment involves biological and protein-specific analytical characterization, including identity, purity, aggregation, charge variants, molecular characteristics, potency and other critical quality attributes.
The marketed VYEPTI product is a sterile, preservative-free, clear to slightly opalescent solution for intravenous infusion. The U.S. formulation is supplied at 100 mg/mL and has a formulation pH of 5.8.
Eptinezumab drug substance should be manufactured and tested using validated analytical methods appropriate for monoclonal antibodies. Relevant quality attributes may include:
Storage conditions for eptinezumab drug substance should follow the approved manufacturer's specification and stability data. The finished VYEPTI product has specific refrigerated storage requirements and should be handled according to its approved product labeling.
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |
| Melting Point | 150°C – 154°C |