FDA Approves Sonidegib (Odomzo) for Basal Cell Carcinoma
The US Food and Drug Administration (FDA) has approved the once-a-day 200 mg oral therapy sonidegib (Odomzo, Novartis) for the treatment of locally advanced basal cell carcinoma, which accounts for approximately 80% of nonmelanoma skin cancers.
The indication is for adults whose disease has recurred after surgery or radiation therapy and for patients who are not candidates for surgery or radiation therapy.
Sonidegib inhibits the Hedgehog signaling pathway, which in turn could stop or reduce the growth of the cancerous lesions.
This is the second such drug that the FDA has approved for the treatment of basal cell carcinoma. The first — vismodegib (Erivedge, Genentech/Roche), another Hedgehog pathway inhibitor — was approved in 2012 and is indicated for the treatment of locally advanced and metastatic disease.
"Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed," Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in a press statement.
Sonidegib was recently recommended for approval in Europe. In June, the European Committee for Medicinal Products for Human Use issued a positive opinion for use of the drug in the treatment of advanced basal cell carcinoma.
The efficacy of sonidegib was established in the recently published multicenter double-blind clinical trial of patients with locally advanced basal cell carcinoma, known as BOLT (Basal Cell Carcinoma Outcomes in LDE225 Trial) (Lancet Oncol. 2015;16:716-728).
A total of 66 patients were randomly assigned to receive sonidegib 200 mg daily — the now-approved dosage — and 128 patients were assigned to receive sonidegib 800 mg daily.
The study's primary end point was the objective response rate, or the percentage of patients who experienced partial shrinkage or complete disappearance of their tumor(s).
For the 66 patients in the 200 mg group, the objective response rate was 58%; three patients (5%) achieved a complete response and 35 (53%) achieved a partial response. The duration of response ranged from 1.9 to 18.6 months, and in approximately half of the responding patients, the tumor shrinkage lasted at least 6 months.
Response rates were similar in the 800 mg group, but adverse effects were more common at the higher dose.
The most serious risks with sonidegib are embryo-fetal toxicity and musculoskeletal adverse reactions, including rhabdomyolysis.
As a result, sonidegib carries a boxed warning alerting healthcare professionals that the drug can cause death or severe birth defects in a developing fetus when administered to a pregnant woman. Men taking sonidegib should not donate semen while taking the drug and for at least 8 months after their final dose.
In addition, musculoskeletal adverse reactions can be accompanied by elevations in serum creatine kinase. In the 200 mg group, incidence of musculoskeletal adverse reactions in patients with locally advanced basal cell carcinoma was 68%, and 9% were grade 3 or 4.
In the 200 mg group, adverse reactions that occurred in more than 10% of patients included 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 laboratory abnormalities occurring in at least 5% of patients were serum creatine kinase elevation and lipase elevation.
According to the National Cancer Institute, the number of new cases of nonmelanoma skin cancer each year appears to be increasing in the United States.
The US Food and Drug Administration (FDA) has approved the once-a-day 200 mg oral therapy sonidegib (Odomzo, Novartis) for the treatment of locally advanced basal cell carcinoma, which accounts for approximately 80% of nonmelanoma skin cancers.
The indication is for adults whose disease has recurred after surgery or radiation therapy and for patients who are not candidates for surgery or radiation therapy.
Sonidegib inhibits the Hedgehog signaling pathway, which in turn could stop or reduce the growth of the cancerous lesions.
This is the second such drug that the FDA has approved for the treatment of basal cell carcinoma. The first — vismodegib (Erivedge, Genentech/Roche), another Hedgehog pathway inhibitor — was approved in 2012 and is indicated for the treatment of locally advanced and metastatic disease.
"Our increasing understanding of molecular pathways involved in cancer has led to approvals of many oncology drugs in difficult-to-treat diseases for which few therapeutic options previously existed," Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in a press statement.
Sonidegib was recently recommended for approval in Europe. In June, the European Committee for Medicinal Products for Human Use issued a positive opinion for use of the drug in the treatment of advanced basal cell carcinoma.
The efficacy of sonidegib was established in the recently published multicenter double-blind clinical trial of patients with locally advanced basal cell carcinoma, known as BOLT (Basal Cell Carcinoma Outcomes in LDE225 Trial) (Lancet Oncol. 2015;16:716-728).
A total of 66 patients were randomly assigned to receive sonidegib 200 mg daily — the now-approved dosage — and 128 patients were assigned to receive sonidegib 800 mg daily.
The study's primary end point was the objective response rate, or the percentage of patients who experienced partial shrinkage or complete disappearance of their tumor(s).
For the 66 patients in the 200 mg group, the objective response rate was 58%; three patients (5%) achieved a complete response and 35 (53%) achieved a partial response. The duration of response ranged from 1.9 to 18.6 months, and in approximately half of the responding patients, the tumor shrinkage lasted at least 6 months.
Response rates were similar in the 800 mg group, but adverse effects were more common at the higher dose.
The most serious risks with sonidegib are embryo-fetal toxicity and musculoskeletal adverse reactions, including rhabdomyolysis.
As a result, sonidegib carries a boxed warning alerting healthcare professionals that the drug can cause death or severe birth defects in a developing fetus when administered to a pregnant woman. Men taking sonidegib should not donate semen while taking the drug and for at least 8 months after their final dose.
In addition, musculoskeletal adverse reactions can be accompanied by elevations in serum creatine kinase. In the 200 mg group, incidence of musculoskeletal adverse reactions in patients with locally advanced basal cell carcinoma was 68%, and 9% were grade 3 or 4.
In the 200 mg group, adverse reactions that occurred in more than 10% of patients included 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 laboratory abnormalities occurring in at least 5% of patients were serum creatine kinase elevation and lipase elevation.
According to the National Cancer Institute, the number of new cases of nonmelanoma skin cancer each year appears to be increasing in the United States.
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