Vanzacaftor is a synthetic small-molecule CFTR corrector used in combination with other CFTR modulators for the treatment of cystic fibrosis in patients with responsive CFTR mutations. It was developed by Vertex Pharmaceuticals as VX-121 and is one of the active components of Alyftrek, in combination with tezacaftor and deutivacaftor. Vanzacaftor was first approved by the U.S. FDA in December 2024.
Vanzacaftor is identified as CAS No. 2374124-49-7, with molecular formula C32H39N7O4S and molecular weight 617.8 g/mol for the parent compound. Its FDA-approved pharmaceutical form, however, is vanzacaftor calcium dihydrate. The FDA label describes the active pharmaceutical substance as a calcium salt with the formula C32H38N7O4S·Ca0.5·H2O and molecular weight 654.82 g/mol.
For pharmaceutical manufacturing, it is important not to confuse the parent compound Vanzacaftor with the marketed Vanzacaftor Calcium Dihydrate.
The FDA describes vanzacaftor calcium dihydrate as a white solid that is practically insoluble in water, with solubility below 0.1 mg/mL.
PubChem identifies vanzacaftor calcium dihydrate with molecular formula C64H80CaN14O10S2 and molecular weight 1309.6 g/mol for the full two-vanzacaftor-unit calcium dihydrate representation.
For an API product page, the pharmaceutical form should therefore be clearly identified according to the material actually being supplied.
Vanzacaftor is a CFTR corrector. CFTR, or cystic fibrosis transmembrane conductance regulator, is an ion channel involved in chloride and bicarbonate transport across epithelial cell membranes.
Vanzacaftor acts at a different site from tezacaftor and helps increase the amount of functional CFTR protein reaching the cell surface. Deutivacaftor, the third component of Alyftrek, acts as a CFTR potentiator to increase channel activity. The combination therefore addresses different aspects of defective CFTR protein function.
Vanzacaftor, in combination with tezacaftor and deutivacaftor, is indicated for the treatment of cystic fibrosis in patients 6 years of age and older who have at least one F508del mutation or another CFTR mutation responsive to the combination.
The approved product is administered orally as a fixed-dose combination tablet. The development of vanzacaftor represents an important advancement in CFTR modulator therapy because it is designed to work together with a complementary corrector and potentiator.
The parent Vanzacaftor molecule has:
PubChem confirms CAS 2374124-49-7, molecular formula C32H39N7O4S, molecular weight 617.8 g/mol and UNII COM1POP492.
The FDA-approved pharmaceutical form is vanzacaftor calcium dihydrate, which is described as a white solid and is practically insoluble in water (<0.1 mg/mL).
Because the marketed pharmaceutical form is a calcium salt dihydrate, the calcium salt form should be distinguished from the parent Vanzacaftor when documenting API identity, molecular weight, stoichiometry and analytical specifications.
Vanzacaftor is a relatively new pharmaceutical substance and I could not verify a current publicly available USP or Ph. Eur. monograph establishing universal numerical release specifications for the API.
Therefore, values such as 98–102% assay, LOD NMT 0.5%, residue on ignition NMT 0.1%, or specific impurity limits should not be presented as official compendial specifications unless supported by the applicable approved API specification.
For pharmaceutical manufacturing, the specification should appropriately control identity, assay, related substances, stereochemical purity, water, residual solvents, elemental impurities and solid-state characteristics as applicable.
Swapnroop Drugs & Pharmaceuticals can position Vanzacaftor as a specialized pharmaceutical API for CFTR-modulator and cystic-fibrosis pharmaceutical development.
As a Vanzacaftor API manufacturer and supplier in India, the product can be supplied according to an applicable pharmaceutical specification with appropriate analytical documentation.
Typical documentation may include:
The storage requirements should be based on the approved API stability program and specification. The material should be protected from unsuitable environmental conditions and maintained in appropriate pharmaceutical packaging.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |