e 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.
"We are pleased to have a new treatment option for European patients living with advanced basal cell carcinoma," said Bruno Strigini, President, Novartis Oncology. "This milestone follows the recent approval of Odomzo in the US and is the latest example of our commitment to precision oncology and developing targeted treatments to address unmet needs."
The EU approval follows a positive opinion adopted by the Committee for Medicinal Products for Human Use (CHMP) in June 2015 and applies to all 28 EU member states, plus Iceland, Norway and Liechtenstein. Outside the EU, Odomzo is approved in the United States, Australia and Switzerland. Additional regulatory submissions are being reviewed by health authorities worldwide.
About the BOLT Clinical Trial
The primary endpoint of the BOLT study was ORR of patients treated with Odomzo 200 mg and 800 mg, defined as the proportion of patients with confirmed complete or partial tumor response, or shrinkage, as measured by a central review committee. There was no evidence of better ORR among patients with laBCC randomized to receive Odomzo 800 mg daily. The secondary endpoints included duration of response, time to tumor response and progression-free survival as determined by central review.
Patients with laBCC treated with Odomzo 200 mg (n=66) were followed for at least 18 months unless discontinued earlier. The ORR per central review of 56% (95% confidence interval: 43, 68) consisted of 5% (n=3) complete responses (CR), or 23% using a pre-specified CR assessment similar to other laBCC trials, and 52% (n=34) partial responses (PR). The 71% ORR (95% confidence interval: 59, 82) per investigator review consisted of 9% (n=6) CR and 62% (n=41) PR.
The eva luation of tumor response was based on a composite assessment of modified Response eva luation Criteria in Solid Tumors (mRECIST) that integrated tumor measurements obtained by radiographic assessments of target lesions (per RECIST 1.1), digital clinical photography (World Health Organization (WHO) adapted criteria) and histopathology assessments (via punch biopsies). All modalities used must have demonstrated absence of tumor to achieve a composite assessment of CR.
The most serious risks of Odomzo are embryofetal toxicity and musculoskeletal adverse reactions including rhabdomyolysis. Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase (CK) elevations, may occur with Odomzo and other drugs that inhibit the hedgehog pathway. The incidence of musculoskeletal adverse reactions in patients with laBCC treated with Odomzo 200 mg was 54%, with 8% reported as grade 3 or 4. Adverse reactions occurring in more than 10% of patients treated with Odomzo 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting and pruritus. The most frequent grade 3 and 4 adverse reactions occurring in at least 2% of patients treated with Odomzo 200 mg were fatigue, decre
