Differentiating the Two Approved Hedgehog Inhibitors in BCC

This episode, " Differentiating the Two Approved Hedgehog Inhibitors in BCC," features Dr. Singh walking through how he presents the two approved agents to patients.

Dr. Singh explains that patient preference is always the first consideration in his practice. He reviews efficacy data with patients, including trial results and the differences between trials, and often invites caregivers and family members into the conversation. His goal is to present the evidence in a way that empowers patients to reach their own decisions.

He is careful to tell every patient that no head-to-head trials compare the two agents. Firm conclusions about their relative efficacy therefore cannot be drawn, and he makes that limitation explicit.

Both drugs are taken orally once daily. Vismodegib is dosed at 150 mg per day, and sonidegib at 200 mg per day. Dr. Singh notes that the BOLT trial of sonidegib permitted drug holidays of up to 21 days. He shares this with patients who worry about adverse effects or about remembering a daily medication, since it offers some reassurance about flexibility.

He then turns to pharmacokinetics, which he discusses with patients in plain language. Sonidegib has a very high volume of distribution and a half-life of about 1 month. Vismodegib has a half-life of roughly 4 to 12 days. Sonidegib takes up to 4 months to reach steady state, compared with about 3 weeks for vismodegib.

To make these numbers meaningful, Dr. Singh relies on an analogy. He tells patients that sonidegib goes to the scene of the crime, meaning the tumor in the skin, and then stays there. He describes it as forming a wall that keeps working. Most patients do not want a lecture on volume of distribution. However, he explains that the high volume of distribution means the drug acts in adipose tissue and skin, where the pathology actually exists.

Our next episode, "Monitoring Safety with Hedgehog Inhibitors in BCC," turns to laboratory monitoring, the timing of adverse events, and emerging strategies to address resistance.