Date: 2015-08-20
Type of information: Granting of a Market Authorisation in the EU
Product name: Odomzo®
Compound: sonidegib - LDE225
Therapeutic area: Cancer - Oncology
Action mechanism:
- hedgehog signaling inhibitor. LDE225 (sonidegib) is an oral, investigational, selective smoothened inhibitor being studied in a variety of cancers. This GPCR-like (G protein-coupled receptor) binds to smoothened receptors and prevents abnormal activation of the Hedgehog pathway, which is associated with uncontrolled cellular growth and proliferation.
Company: Novartis (Switzerland)
Disease: loally advanced basal cell carcinoma
Latest news:
- • On August 20, 2015, Novartis announced that the European Commission has approved Odomzo® (sonidegib, formerly LDE225) 200 mg capsules for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) who are not amenable to curative surgery or radiation therapy. The EU approval of Odomzo® was based on data from the Phase II randomized, double-blind, multi-center BOLT (Basal cell carcinoma Outcomes in LDE225 Trial) study in patients with laBCC not amenable to local therapy or metastatic basal cell carcinoma (mBCC). In patients with laBCC treated with Odomzo® 200 mg, the objective response rate (ORR) was 56% per central review and 71% per investigator review. The median duration of response per central review has not been reached. The median progression-free survival was 22 months per central review and 19 months per investigator review. The most frequent grade 3 and 4 adverse reactions occurring in at least 2% of patients treated with Odomzo 200 mg were fatigue, decreased weight and muscle spasms.
- • On July 24, 2015, the FDA approved Odomzo® (sonidegib) to treat patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or who are not candidates for surgery or radiation therapy. Odomzo® is a pill taken once a day. In 2012, Erivedge® (vismodegib) was the first drug approved to treat locally advanced and metastatic basal cell carcinoma.
- Odomzo® carries a Boxed Warning alerting healthcare professionals that Odomzo® may cause death or severe birth defects in a developing fetus when administered to a pregnant woman. Pregnancy status should be verified prior to the start of Odomzo® treatment, and both male and female patients should be warned about these risks and advised to use effective contraception.
- The efficacy of Odomzo® was established in a multi-center, double-blind clinical trial, in which 66 patients with locally advanced basal cell carcinoma were randomly assigned to receive Odomzo® 200 mg daily and 128 patients were assigned to receive Odomzo® 800 mg daily. The study’s primary endpoint was objective response rate, which is the percentage of patients who experienced partial shrinkage or complete disappearance of their tumor(s). Results showed that 58 percent of patients treated with Odomzo® 200 mg had their tumors shrink or disappear. This effect lasted at least 1.9 to 18.6 months, and approximately half of the responding patients’ tumor shrinkage lasted six months or longer. Response rates were similar in patients who received Odomzo 800 mg daily, however side effects were more common at this dose.
- • On 25 June 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Odomzo®, intended for the treatment of adults with locally advanced basal cell carcinoma (BCC). Odomzo® will be available as 200 mg hard capsules. The benefits with Odomzo® are its ability to reduce locally advanced BCC lesions, with a response rate of about 54% and a progression-free survival of approximately 22 months. The most common side effects of Odomzo® treatment are muscle cramps, muscle pain, hair loss, alteration or loss of taste, nausea, diarrhoea, blood creatine phosphokinase increased weight decrease and fatigue. A pregnancy prevention plan and a pharmacovigilance plan for Odomzo will be implemented as part of the marketing authorisation.
- The full indication is: "Odomzo® is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) who are not amenable to curative surgery or radiation therapy." It is proposed that Odomzo® should only be prescribed by or under the supervision of a specialist physician experienced in the management of the approved indication.
- LDE225 was submitted in the EU in the second quarter of 2014 and in the US in the third quarter of 2014.
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: 2015-07-24
UE authorization: 2015-08-14
Favourable opinion UE: 2015-06-25
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
