Pharmacological Class:
Hedgehog pathway inhibitor.

Active Ingredient(s):
Sonidegib 200mg; capsules.

Company
Novartis Pharmaceuticals Corp
Indication(s):
Treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

Pharmacology:
Sonidegib inhibits the Hedgehog pathway by binding to and inhibiting Smoothened, a transmembrane protein involved in Hedgehog signal transduction.

Clinical Trials:
The safety and efficacy of Odomzo were eva luated in a single, multicenter, double-blind, multiple cohort trial conducted in patients with locally advanced basal cell carcinoma (laBCC) (n=194) or metastatic basal cell carcinoma (mBCC) (n=36). Patients were randomized (2:1) to receive either Odomzo 800mg or 200mg once daily until disease progression or intolerable toxicity. Randomization was stratified by stage of disease (locally advanced or metastatic), laBCC disease histology (aggressive vs. non-aggressive), and geographic region.

The major efficacy outcome measure of the trial was objective response rate (ORR) as determined by blinded central review according to modified Response eva luation Criteria in Solid Tumors (mRECIST) for laBCC patients or RECIST version 1.1 for mBCC patients. Duration of response (DOR), determined by blinded central review, was a key secondary outcome measure.

A total of 66 patients with laBCC randomized to receive Odomzo 200mg daily were followed for at least 12 months unless discontinued earlier. At endpoint, the ORR was 58% (95% CI: 45, 70), consisting of 3 (5%) complete responses and 35 (53%) partial responses. Among the 38 patients with an objective response, 7 (18%) experienced subsequent disease progression with 4 out of 7 patients having maintained a response of 6 months or longer. The remaining 31 patients (82%) have ongoing responses ranging from 1.9+ to 18.6+ months and the median duration of response has not been reached.

A total of 128 patients randomized to Odomzo 800mg daily had laBCC. Twelve of these patients had a diagnosis of Gorlin Syndrome. There was no evidence of better antitumor activity (ORR) among patients with laBCC randomized to receive Odomzo 800mg daily and followed for at least 12 months unless discontinued earlier.

For more clinical trial data, see full labeling.

Legal Classification:
Rx

Adults:
Take on empty stomach. 200mg once daily until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children:
Not established.

Warnings/Precautions:
Risk of embryo-fetal death or severe birth defects in pregnant women. Verify pregnancy status of females of reproductive potential prior to initiation. Advise females to use effective contraception during therapy and for at least 20 months after the last dose; male patients must use condoms and not to donate semen during therapy and for at least 8 months after last dose. Advise patients not to donate blood or blood products during therapy and for at least 20 months after last dose. Risk of musculoskeletal adverse reactions accompanied by serum creatine kinase (CK) elevations. Obtain baseline serum CK and creatinine (SCr) levels prior to initiation; periodically during treatment and as clinically indicated. Obtain serum CK and SCr levels at least weekly in those with musculoskeletal adverse reactions with concurrent serum CK elevation >2.5XULN until symptoms resolve. Pregnancy. Nursing mothers: not recommended during therapy and for 20 months after last dose.

Interaction(s)
Avoid concomitant strong CYP3A inhibitors (eg, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone) or moderate CYP3A inhibitors (eg, atazanavir, diltiazem, fluconazole); if moderate CYP3A inhibitor use necessary, administer for <14 days and monitor closely. Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort).

Adverse Reaction(s)
Muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, pruritus; anemia, hyperglycemia, increased SCr, CK, and LFTs.

How Supplied:
Caps—30

LAST UPDATED:
10/26/2015