FDA approves Odomzo for locally advanced basal cell carcinoma

The FDA today announced the approval of sonidegib for the treatment of patients with locally advanced basal cell carcinoma.

Sonidegib (Odomzo, Novartis Pharmaceuticals) is indicated for patients whose basal cell carcinoma has advanced following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation.

The FDA based its decision in part on the results of an international multicenter, double-blind, non-comparative randomized trial of 230 patients with metastatic basal cell carcinoma or locally advanced basal cell carcinoma not amenable to local therapies.

Researchers randomly assigned patients to receive 800-mg (n = 151) or 200-mg (n = 79) doses of daily sonidegib until disease progression or unacceptable toxicity.

The 200-mg dose arm included 66 patients with locally advanced disease. Of these patients,

76% had been previously treated and 56% had aggressive histology.

The overall response rate (ORR) among these 66 patients was 58% (95% CI, 45-70). Three patients (5%) achieved a complete response and 35 patients (53%) achieved a partial response.

Results of a prespecified sensitivity analysis that used an alternative definition of complete response — or at least a partial response according to MRI and no tumor evidence on biopsy of the residual lesion — demonstrated a complete response rate of 20%.

Seven of the 38 responding patients in the 200-mg cohort subsequently experienced disease progression, four of whom had maintained a response for 6 or more months. Responses are ongoing in the other 31 patients, and the median duration of response has not yet been reached (range, 1.9+ to 18.6+ months).

The ORR among 128 patients with locally advanced basal cell carcinoma assigned the 800-mg dose was 44% (95% CI, 35-53).

Serious and common adverse events, as well as study discontinuation due to adverse events, occurred more frequently in the 800-mg arm.

Adverse events occurring in 10% or more of the patients assigned 200 mg included muscle spasms, alopecia, dysgeusia, fatigue, nausea, diarrhea, decreased weight and appetite, headache and vomiting. The most common grade 3 to grade 4 adverse events in the 200-mg cohort were serum lipase and creatine kinase elevations.

Among all 79 patients assigned the 200-mg dose, 68% experienced musculoskeletal adverse reactions, 29% of which required medical intervention and 8% of which warranted treatment discontinuation.

Based on these data, the recommended dose and schedule for sonidegib is 200 mg once daily on an empty stomach, at least 1 hour prior to or 2 hours following a meal.

“The FDA approval of Odomzo offers a new and non-invasive treatment option for a potentially devastating disease that is hard to treat and can be disfiguring,” Bruno Strigini, PharmD, MBA, president of Novartis Oncology, said in a press release. “Odomzo is an important addition to our growing portfolio of targeted treatments for advanced skin cancers and underscores our commitment to developing and bringing to market new options for patients.”