Erivedge™ (vismodegib) Capsule in Advanced Basal Cell Carcinoma
Erivedge (vismodegib) capsule is the first and only oral medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation (pronounced "EH-rih-vej" and "vis-mo-DEJ-ib").1
What is Advanced Basal Cell Carcinoma?
- BCC is the most common type of skin cancer and is generally curable if the cancer is restricted to a small area of the skin. In rare cases, lesions can become disfiguring and invade surrounding tissue (locally advanced) or spread to other part of the body (metastasize)2
- In these cases of advanced BCC, the disease cannot be effectively treated with surgery or radiation3,4
- Advanced BCC often results in severe deformity or loss of function of affected organs3,4
What is the Hedgehog Pathway?
- The Hedgehog pathway was first discovered in fruit flies. It was named because mutations in a gene caused a developing fruit fly to look curled up and spiky, resembling a hedgehog. A similar signaling pathway was discovered in humans and the name carried over 5
- The Hedgehog pathway plays an important role in regulating proper growth and development of tissues and organs during the early stages of life and then becomes less active in adults6
- In particular, mutations in Patched or Smoothened, key proteins in Hedgehog signaling, are believed to lead to cancer cell growth5,7
- Erivedge is a Hedgehog pathway inhibitor indicated for the treatment of adults with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation1
(1) First, the Hedgehog protein binds to a receptor protein, or dock, called Patched that is found on the cell surface
(2) After Hedgehog binds Patched, both proteins move inside the cell
(3) When Patched moves inside the cell, a protein called Smoothened is activated
(4) The Smoothened protein then moves to the cell surface
(5) When Smoothened moves to the cell surface, it activates other proteins
(6) These proteins ultimately turn on genes involved in cell growth and survival
How Erivedge May Work (Proposed Mechanism of Action)
- Erivedge is designed to selectively inhibit the Hedgehog pathway by binding the Smoothened protein and interfering with cell growth and survival1,5
- Genentech scientists have made important discoveries about the underlying biology of the Hedgehog pathway and its relationship to cancer. These include the identification of the Smoothened protein, a key protein in the pathway, and the role of abnormal Hedgehog signaling in BCC9
- Erivedge can cause harm to the embryo or fetus based on its mechanism of action
Erivedge is designed to selectively bind to the Smoothened protein. When this occurs, signaling is inhibited and the Hedgehog pathway is deactivated.
Erivedge in Advanced Basal Cell Carcinoma 1
The FDA approval of Erivedge is based on results from an international, single-arm, multicenter, open-label, two-cohort, pivotal study (ERIVANCE BCC/SHH4476g) that enrolled 104 patients with either locally advanced BCC (71) and metastatic BCC (33). Results showed that:
- Erivedge shrank lesions (objective response rate, or ORR) in 43 percent of patients (27/63) with locally advanced BCC and 30 percent of patients (10/33) with metastatic BCC, as assessed by independent review
- Erivedge can cause a baby to die before it is born (be stillborn) or cause a baby to have severe birth defects based on how the medicine interacts with the body. See full prescribing information for complete boxed warning
- The most serious adverse reactions (Grade 3 or higher; incidence of greater than or equal to 10 percent) were weight loss (7.2 percent), fatigue (5.8 percent), muscle spasms (3.6 percent), decreased appetite (2.2 percent), nausea (0.7 percent), diarrhea (0.7 percent) and arthralgias (joint aches; 0.7 percent)
- The most common adverse events (incidence of greater than or equal to 10 percent) were muscle spasms, alopecia (hair loss), dysguesia (altered taste), weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias (joint aches), vomiting and ageusia (lack of taste)
Erivedge Development Program
- Genentech continues to study Erivedge in clinical trials of BCC
- Visit www.clinicaltrials.gov for a list of ongoing Erivedge clinical studies
- For additional information on Erivedge please visit www.erivedge.com
Indication
Erivedge is a prescription medicine used to treat adults with a type of skin cancer, called basal cell carcinoma, that has spread to other parts of the body or that has come back after surgery or that their healthcare provider decides cannot be treated with surgery or radiation.
Important Safety Information and Serious Side Effects
- Erivedge can cause your baby to die before it is born (be stillborn) or cause your baby to have severe birth defects
- For females who can become pregnant, talk with your healthcare provider about the risks of Erivedge to your unborn child. Your healthcare provider should do a pregnancy test within 7 days before you start taking Erivedge to find out if you are pregnant. Avoid pregnancy by using highly effective birth control before starting Erivedge, and continue during treatment and for 7 months after your last dose. Tell your healthcare provider right away if you have unprotected sex or think that your birth control has failed. For males, always use a condom with a spermicide during sex with female partners while you are taking Erivedge and for 2 months after your last dose, even if you have had a vasectomy
- Tell your healthcare provider right away if you or your female partner could be pregnant or thinks she is pregnant while you are taking Erivedge
Exposure to Erivedge during pregnancy:
Pregnant women are encouraged to participate in a program that collects information about exposure and the effects on the mother and her unborn child by calling the Genentech Adverse Event Line at (888) 835-2555.
What should I tell my healthcare provider before taking Erivedge?
- If you are pregnant or plan to become pregnant
- If you are breast-feeding or plan to breast-feed
What should I avoid while taking Erivedge?
Do not donate blood or blood products while you are taking Erivedge and for 7 months after your last dose.
What are the possible side effects of Erivedge?
The most common side effects of Erivedge are
- Muscle spasms
- Hair loss
- Change in how things taste or loss of taste
- Weight loss
- Tiredness
- Nausea
- Diarrhea
- Decreased appetite
- Constipation
- Vomiting
- Joint aches
These are not all of the possible side effects of Erivedge. For more information, ask your healthcare provider or pharmacist. Because everyone is different, it is not possible to predict what side effects any one person will have or how severe they may be. If you have questions or concerns about side effects, you should talk to your doctor.
Please see the full Prescribing Information and the Medication Guide that come with this [booklet, letter, etc] for serious side effects and additional important safety information.
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