Sonidegib (Odomzo) Approved for Basal Cell Carcinoma in EU

Zosia Chustecka


August 20, 2015

The European Commission has approved sonidegib (Odomzo, Novartis) for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) who are not amenable to curative surgery or radiation therapy. The approval follows a positive opinion issued in June.

The drug was recently approved in the United States, in July, for a similar indication.

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 approved for the treatment of basal cell carcinoma. The first — vismodegib (Erivedge, Genentech/Roche), another Hedgehog pathway inhibitor — was approved in 2012 in the United States. This drug was hailed as the "greatest advance in therapy for BCC" at that time.

Basal cell carcinoma (BCC) is the most common type of skin cancer, accounting for more than 80% of nonmelanoma skin cancers. It consists of abnormal uncontrolled growths or lesions that arise in the skin's basal cells, which line the deepest layer of the epidermis. Although BCC rarely becomes advanced (in about 1% - 10% of cases), there have been few treatment options at this stage of the disease, according to the manufacturer.

"I have seen first-hand the devastating impact advanced basal cell carcinoma can have on those living with the disease. As the lesions are usually highly visible and located predominantly on the face, they can impact patients both physically and emotionally," Reinhard Dummer, MD, professor of dermatology at the University of Zurich, commented in a company press release.

"The approval of sonidegib brings new hope in the form of a noninvasive option to help treat this disfiguring and potentially life-threatening disease," he said.

The approval was based on data from the phase 2 Basal Cell Carcinoma Outcomes in LDE225 (later named sonidegib) Trial (BOLT). The study was conducted in patients with laBCC not amenable to local therapy or with metastatic BCC, and investigated two doses of the drug: 200 mg and 800 mg. The higher dose was no more beneficial, and the approval was based on data for the lower dose of sonidegib 200 mg in 66 patients with laBCC, who were followed for at least 18 months unless they discontinued early.

In this cohort of 66 patients, the objective response rate (ORR) was 56% per central review (comprised of three complete responses [CR] and 34 partial responses [PR]) and was 71% per investigator review (comprising six CR and 41 PR).

The ORR was the primary end point, and evaluation of tumor response was based on a composite assessment of modified Response Evaluation 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–adapted criteria), and histopathology assessments (via punch biopsies). All modalities used must have demonstrated absence of tumor to achieve a composite assessment of CR. These criteria were more stringent than those used in the pivotal study of vismodegib, a researcher who was involved in both studies told Medscape Medical News earlier this year when the BOLT study was published. In addition, the vismodegib study included patients with metastatic BCC, so the two studies cannot be compared directly, said Michael R. Migden, MD, from the Mohs Surgery Center, Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Houston.

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 sonidegib 200 mg were fatigue, decreased weight, and muscle spasms. Adverse reactions occurring in more than 10% of patients treated with sonidegib 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 manufacturer notes that musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase elevations, appear to be a class effect as they may also occur with other drugs that inhibit the Hedgehog pathway. The incidence of musculoskeletal adverse reactions in patients with laBCC treated with sonidegib 200 mg was 54%, with 8% reported as grade 3 or 4.


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