AusPAR: Cabazitaxel - Therapeutic Goods Administration

I. Introduction to Product Submission
Submission Details
Type of Submission: New Chemical Entity
Decision: Approved
Date of Decision: 5 December 2011
Active ingredient(s): Cabazitaxel (as acetone solvate)
AusPAR Jevtana Cabazitaxel Sanofi-Aventis Australia Pty Ltd PM-2010-02565-3-4
Final 9 February 2012
Therapeutic Goods Administration
Product Name(s): Jevtana, Cabazitaxel Winthrop, Cabazitaxel Sanofi
Sponsor’s Name and Address: Sanofi-Aventis Australia Pty Ltd
Dose form(s): Concentrated Injection
Strength(s): 60 mg/1.5 mL
Container(s): 1.5 mL vial with a 4.5 mL diluent vial
Pack size(s): One pack contains the concentrate and diluent vial.
Approved Therapeutic use: In combination with prednisone or prednisolone for the treatment
of patients with hormone refractory metastatic prostate cancer
previously treated with a docetaxel containing regimen.
Route(s) of administration: Intravenous
Dosage: 25 mg/m 2 1h infusion every 3 weeks with oral prednisone or
prednisolone 10 mg daily throughout treatment
ARTG Number (s): Awaiting ARTG inclusion
Product Background
Cabazitaxel is a semisynthetic compound derivative from 10-deacetylbaccatin III, which is
extracted from European yew needles. This new taxane, which promotes the tubulin
assembly in vitro and stabilises microtubules against cold induced depolymerisation as
efficiently as docetaxel, was selected for development based on a better anti-proliferative
activity on resistant cell lines than docetaxel. Using cell lines with acquired resistance to
doxorubicin, vincristine, vinblastine, paclitaxel and docetaxel, the resistance factors
ranged from 1.8 to 10 and 4.8 to 59, for cabazitaxel and for docetaxel, respectively.
Cabazitaxel exhibited a broad spectrum of in vivo antitumour activity, not only in docetaxel
sensitive tumour models, but also in tumour models in which docetaxel was poorly or not
active. In addition, this compound was found to penetrate the blood brain barrier and
marked antitumor activity was obtained in nude mice bearing intracranial glioblastomas.
Prostate cancer is a major worldwide health problem. The initial treatment for metastatic
adenocarcinoma of the prostate consists of androgen ablation, either surgically with
bilateral orchiectomy or medically with luteinizing hormone releasing hormone (LH-RH)
receptor agonists. Responses are observed in up to 85% of patients. At this stage, further
hormonal manipulations such as treatment with antiandrogens, and subsequent
antiandrogen withdrawal can be associated with responses of short duration but without
improvement in survival duration. Treatment options for patients with hormone
refractory disease remain limited and include palliation of symptoms (especially pain)
and/or systemic cytotoxic chemotherapy. Once a patient progresses to metastatic
Page 4 of 75