Regulatory Decision Summary for Odomzo

Locally advanced basal cell carcinoma (laBCC) that is not amenable to radiation therapy or curative surgery is a serious disease. Local tissue invasion and destruction by the tumour results in considerable morbidities, including disfigurement. The majority of BCCs contain genetic alterations in the Hedgehog (Hh) signaling pathway, resulting in aberrant pathway activation and uncontrolled proliferation of BCC cells.

The efficacy and safety of Odomzo (sonidegib) were evaluated in a phase II pivotal clinical trial BOLT. Sixty-six patients with locally advanced basal cell carcinoma (laBCC) received Odomzo 200 mg once daily. Based on the primary (6-month) analysis, the objective response rate (ORR) was 47% (95% confidence interval [CI]: 35%, 60%), as determined by blinded central review according to modified Response Evaluation Criteria in Solid Tumours (mRECIST). The median duration of response (DOR) was not estimable. At the 42-month analysis, the ORR was 56% (95% CI: 43%, 68%), and the median DOR was 26.1 months. The ORR, supported by the DOR, is considered clinically meaningful.

The most common adverse reactions occurring in ≥10% of patients treated with Odomzo 200 mg once daily were muscle spasms, alopecia, fatigue, dysgeusia, nausea, musculoskeletal pain, diarrhea, weight decreased, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting and pruritus. The most common severe adverse reactions occurring in ≥ 2% of the patients were fatigue, weight decreased, muscle spasms and hypotension. Increased serum creatine phosphokinase (CPK) laboratory values occurred in 61% (48/79) of patients with 8% (6/79) of patients having Grade 3 or 4 serum CPK elevations. The adverse reactions were generally manageable by close monitoring, symptomatic treatment, and Odomzo treatment interruption or discontinuation.

Odomzo can cause amenorrhea (absence of menstrual periods) in female patients who are able to become pregnant. It is not known if amenorrhea is permanent. Based on non-clinical studies, Odomzo may irreversibly impair fertility. Fertility preservation strategies should be discussed with female patients of childbearing potential prior to starting treatment with Odomzo.

In non-clinical studies, sonidegib was embryotoxic, fetotoxic and teratogenic at maternal exposures below the recommended human dose of 200 mg. To prevent the risk of embryo-fetal toxicity, Odomzo is only available through a controlled distribution program called the Odomzo Pregnancy Prevention Program (OPPP). Under this program, only prescribers and pharmacies registered with the program are able to prescribe and dispense the product, respectively. In addition, Odomzo can only be dispensed to patients who are registered and meet all the conditions of the OPPP.

The safety information and relevant risk management recommendations are adequately described in the approved Product Monograph.

A Risk Management Plan (RMP), including OPPP documents, was reviewed by the Marketed Health Products Directorate and is considered acceptable.

Overall, including consideration of the above risk management measures, the benefit-harm-uncertainty profile of Odomzo is considered favorable for the treatment of adult patients with histologically confirmed laBCC not amenable to radiation therapy or curative surgery.