Building Confidence with Hedgehog Inhibitors: Tips from the Clinic

This video is sponsored by Sun Pharma. Its content is editorially independent of the sponsor.

In this episode of Topical Conversations, Brent Moody, MD, and Scott Dinehart, MD, discuss the use of hedgehog inhibitors, particularly sonidegib, in the management of advanced basal cell carcinoma (BCC). While many dermatologists remain hesitant to incorporate these agents into practice, the conversation highlights how thoughtful strategies can improve both clinician comfort and patient outcomes.

When does it make sense to use hedgehog inhibitors?

Dr Moody explains that hedgehog inhibitors are especially valuable in 2 categories of patients: those with large tumors or multiple BCCs where surgery is impractical or would create significant functional or cosmetic challenges, and patients experiencing “surgical fatigue,” where repeated procedures are no longer feasible or acceptable.

Dr Dinehart adds further scenarios, such as patients in nursing home, those with significant comorbidities, and individuals requiring neoadjuvant therapy to shrink tumors before surgery. Both physicians stress that these agents can also play an important role in palliative care, such as stopping bleeding lesions in elderly patients.

Addressing misconceptions and efficacy

One of the most persistent myths, according to Dr Dinehart, is that hedgehog inhibitors “don’t work.” In his experience, more than 90% of appropriately selected patients benefit. Both physicians emphasize that efficacy is not the limitation; rather, tolerability and adverse events tend to drive discontinuation.

Managing adverse events with tailored dosing strategies

The most common adverse events with sonidegib (muscle cramps, hair loss, taste disturbances, and fatigue) can be mitigated with proactive management. Both Drs Dinehart and Moody address this through tailored dosing strategies.  

Dr Dinehart begins patients on L-carnitine before treatment and transitions to a twice-weekly sonidegib regimen after the first month of standard dosing. Dr Moody also initiates L-carnitine but follows a different pattern: daily sonidegib treatment for 1–2 months alternated with 1–2 months off-drug, typically for 3 cycles, which he usually finds sufficient to achieve satisfactory clinical response. He then maintains patients on once-weekly dosing for one year.  

Despite differing approaches, both physicians emphasize that individualized regimens can balance efficacy with improved tolerability.

Practical considerations

Both doctors recommend baseline labs, particularly creatinine and creatine phosphokinase, before initiating therapy. They also stress appropriate precautions in women of childbearing potential due to teratogenicity and embryotoxicity and avoidance in patients under 18 because of risks related to bone development.

Key takeaways

• Hedgehog inhibitors like sonidegib are highly effective; reluctance often stems from concerns about safety and tolerability rather than efficacy
• Patient selection can be broad: beyond large or difficult tumors, consider nursing home residents, patients with multiple BCCs, those fatigued by repeated surgery, or those needing palliative care
• Side effects are manageable with dose adjustments, intermittent dosing, or prophylactic measures such as L-carnitine
• Dermatologists can and should become comfortable prescribing these agents; clinical experience builds quickly once a few cases are managed