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Part B - Final decisions on matters not referred to an expert advisory committee
5. New Chemical Entities - medicines for human therapeutic use
5.4 Glecaprevir
Delegate's final decision
Final decision:
The delegate has made a final decision to create a new Schedule 4 entry for glecaprevir in the Poisons Standard as follows:
Schedule 4 - New Entry
GLECAPREVIR.
Implementation date: 1 June 2018
Reasons:
The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate include:
- the risks and benefits of the use of a substance
- Glecaprevir is a new chemical entity with no clinical/marketing experience in Australia.
- the purposes for which a substance is to be used and the extent of use of a substance
- Glecaprevir is to be used as an oral fixed dose combination tablet with pibrentasvir for the treatment of chronic hepatitis C infection in adults.
- the toxicity of a substance
- The most common adverse effects observed in clinical trials were headache, fatigue and nausea.
- the dosage, formulation, labelling, packaging and presentation of a substance
- The fixed dose combination tablets of glecaprevir co-formulated with pibrentasvir should be prescribed by medical professionals who are familiar with the management of viral hepatitis. The patients need to be instructed to follow the dosing regimens.
- the potential for abuse of a substance
- Nil.
- any other matters that the Secretary considers necessary to protect public health
- Nil.
Scheduling proposal
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of glecaprevir, a new chemical entity (NCE) for a human therapeutic medicine.
Substance summary
Glecaprevir is a pangenotypic inhibitor of the HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins), and is essential for viral replication. In a biochemical assay, glecaprevir inhibited the proteolytic activity of recombinant NS3/4A enzymes from clinical isolates of HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a with IC50 value ranging from 3.5 to 11.3 nM.
Glecaprevir, co-formulated with pibrentasvir, is indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults.
| Property | Glecaprevir |
|---|---|
| CAS Number | 1365970-03-1 |
| Chemical structure |  |
| Molecular formula | C38H46F4N6O9S (anhydrate) |
| Molecular weight | 838.9 g/mol (anhydrate) |
| Chemical name/s | (3aR,7S,10S,12R,21E,24aR)-7-tert-butyl-N-{(1R,2R)-2-(difluoromethyl)-1-[(1-methylcyclopropane-1-sulfonyl)carbamoyl]cyclopropyl}-20,20-difluoro-5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1H,10H-9,12-methanocyclopenta[18,19][1,10,17,3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10-carboxamide hydrate |
| ANN/INN |
eBS ID: 111184 AAN and INN - glecaprevir |
Scheduling status
Glecaprevir is not specifically scheduled in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) - the Poisons Standard that was in effect at the time the decision was made (Poisons Standard March 2018 (SUSMP No. 20)).
International regulations
Glecaprevir is approved in the USA as a prescription medicine.
Glecaprevir is unclassified in New Zealand and Canada.
Delegate's considerations
The delegate decided to make a delegate-only decision. The Advisory Committee on Medicines Scheduling was not consulted.
The delegate considered the following in regards to this application for scheduling:
- Subsection 52E(1) of the Therapeutic Goods Act 1989;
- The Scheduling Policy Framework scheduling factors;
- The TGA evaluation report;
- The advice of the Advisory Committee on Prescription Medicines; and
- The new drug application.
The delegate noted that currently there are no issues of concern that require additional control other than by inclusion in Schedule 4.