HPBCD in an approved non-replicating adenoviral vector-based gene therapy product

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ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy approved by FDA in December 2022 for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It was developed for intravesical instillation.

It is a recombinant adenovirus serotype 5 vector containing a transgene encoding the human interferon
alfa-2b (IFNα2b). ADSTILADRIN has a nominal concentration of 3 x 1011 vp/mL.

A single-use vial of ADSTILADRIN contains an extractable volume of 20 mL and the following excipients: [N-(3-cholamidopropyl)-N-(3-lactobionamidopropyl)]-cholamide (Syn3, a transduction enhancing agent) (0.95 mg/mL), citric acid monohydrate (0.01 mg/mL), Tri-sodium citrate dihydrate (0.04 mg/mL), polysorbate 80 (Tween 80) (0.48 mg/mL), hydroxypropyl-beta-cyclodextrin (7.9 mg/mL), sodium dihydrogen phosphate dihydrate
(1.4 mg/mL), tromethamine (1.4 mg/mL), sucrose (17 mg/mL), magnesium chloride hexahydrate
(0.34 mg/mL), glycerol (84 mg/mL), and Water for Injection (q.s. 1 mL).

ADSTILADRIN is a sterile, clear to opalescent suspension, and contains no preservative. The combined use of polysorbate 80 and HPBCD in an adenovirus composition is already precedented in Jcovden (previously COVID-19 Vaccine Janssen) vaccine per patent application WO2015040002, wherein the function of cyclodextrin is disclosed as cryoprotectant. Since ADSTILADRIN is shipped frozen at ≤ -60°C, the use of HPBCD due to its cyroprotectant effect is also justified herein.

Second indication of ADSTILADRIN is currently under clinical trial (phase III) in USA for Malignant pleural mesothelioma which is a rare, aggressive cancer of the pleural surface associated with asbestos exposure per patent application US 2020/0164091. 


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