Date: 2012-02-21
Type of information: Granting of a Market Authorisation in the EU
Product name: Caprelsa®
Compound: vandenatib
Therapeutic area: Cancer - Oncology
Action mechanism: kinase inhibitor/tyrosine kinase inhibitor. This tyrosine kinase inhibitor is an antagonist of the vascular endothelial growth factor receptor (VEGFR) and the epidermal growth factor receptor (EGFR).
Company: AstraZeneca (UK)
Disease: medullary thyroid cancer in patients with unresectable (non-operable) locally advanced or metastatic disease
Latest news: * On February 21, 2012, AstraZeneca announced that the European Commission has granted marketing authorisation for Caprelsa® (vandetanib) for the treatment of aggressive and symptomatic medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease. Caprelsa® is the first approved treatment for advanced MTC in Europe. The marketing authorisation is based on data from the Phase III Caprelsa® clinical trial programme, including the ZETA study, a double-blind trial of 331 patients with advanced MTC that has progressed and spread to other parts of the body, which showed a 54 per cent reduction in risk of disease progression compared to placebo (hazard ratio 0.46; 95% CI, 0.31–0.69; P<0.001). Common side effects observed were diarrhoea, rash, headache, fatigue and hypertension. The incidence of protocol-defined QTc prolongation was 14%. * On November 18, 2011, AstraZeneca announced that the Marketing Authorisation Application for Caprelsa® (vandetanib) received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of aggressive and symptomatic medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease. The proposed indication also states that for patients in whom Rearranged during Transfection (RET) mutation is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions. * On April 6, 2011, the FDA has approved the orphan drug vandetanib for the treatment of medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body. The FDA approval of vandetanib is based on the results of the ZETA study, a Phase III, double-blind trial that randomized 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer to vandetanib 300 mg (n=231) or placebo (n=100). In the study, patients randomized to vandetanib showed a statistically significant improvement in progression-free survival (PFS) when compared to those randomized to placebo (Hazard Ratio [HR]=0.35; 95% Confidence Interval [CI]=0.24-0.53; p<0.0001). This difference reflects a 65% reduction in risk for disease progression. Median progression-free survival was 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. At the primary PFS analysis, no significant overall survival difference was noted. QT prolongation, Torsades de pointes, and sudden death are included in the boxed warning for vandetanib. The most common adverse drug reactions (>20%) seen in the ZETA trial with vandetanib were diarrhea (57%), rash (53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), decreased appetite (21%), and abdominal pain (21%).
A Risk Evaluation and Mitigation Strategy (REMS) is required for vandetanib due to the risks of QT prolongation, Torsades de pointes, and sudden death. Only prescribers and pharmacies who are certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense vandetanib.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2011-04-06
UE authorization: 2012-02-21
Favourable opinion UE: 2011-11-18
Favourable opinion USA:
Orphan status USA: 2005-10-21
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
