GENENTECH SCIENTISTS FIRST LINKED THE HEDGEHOG PATHWAY TO CANCER

What is Advanced Basal Cell Carcinoma?

Basal cell carcinoma (BCC) is the most common form of skin cancer. In rare cases, it can become advanced by invading

surrounding tissue (locally advanced) or spread to other parts of the body (metastasize) and cannot be treated with surgery or radiation.^6,8-9

How Erivedge May work BASED ON PRECLINICAL DATA

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 adults.¹⁰

Mutations in Hedgehog signaling, such as in the Patched (PTCH1) or Smoothened (SMO) proteins, are believed to lead to cancer cell growth.^11,12

Erivedge is designed to inhibit the Hedgehog pathway by binding the Smoothened (SMO) protein and interfering with cell signaling.^1,10-12

Erivedge in advanced basal cell carcinoma

ERIVANCE pivotal Phase II study

In a clinical study, 104 adults took Erivedge for their advanced BCC.
Of the 104 patients, 96 were evaluated for objective response rate (63 had locally advanced BCC and 33 had metastatic BCC)

Results at 6 months of Erivedge treatment:

FOR LOCALLY ADVANCED BCC PATIENTS:

43%

(27 patients)

SAW THEIR BCC SHRINK
Out of those, 13 patients saw no visible sign of cancer.

FOR METASTATIC BCC PATIENTS:

30%

(10 patients)

SAW THEIR BCC SHRINK
No patients in this group saw their cancer completely disappear.

How long patients saw improvement:

Half of the patients who responded to Erivedge saw improvement for less than 7.6 months, and half saw improvement for more than 7.6 months.

For patients who responded, the length of improvement ranged from:

1 to 13 months for locally advanced BCC patients
2 to 11 months for metastatic BCC patients

Keep in mind that results may differ. Erivedge can cause side effects, some of which can be serious.

People should talk to their doctor or other healthcare provider about both the benefits and risks of Erivedge.

The most common side effects of Erivedge are:

Muscle spasms	71.7%	Diarrhea	29.0%
Hair loss	63.8%	Decreased appetite	25.4%
Change in taste (dysgeusia)	55.1%	Constipation	21.0%
Weight loss	44.9%	Joint aches	15.9%
Tiredness	39.9%	Vomiting	13.8%
Nausea	30.4%	Loss of taste (ageusia)	10.9%

IMPORTANT SAFETY INFORMATION

Erivedge can cause a patient’s baby to die before it is born (be stillborn) or cause a baby to have severe birth defects.

For females who can become pregnant:

Females who can become pregnant should talk with their healthcare provider about the risks of Erivedge to their unborn child.
Their healthcare provider will do a pregnancy test before the patient starts taking Erivedge.
In order to avoid pregnancy, patients should use birth control during treatment and for 24 months after their final dose of Erivedge. Patients should talk with their healthcare provider about what birth control method is right for them during this time.
Patients must talk to their healthcare provider right away if they have unprotected sex or if they think that their birth control has failed.
Patients must tell their healthcare provider right away if they become pregnant or think that they may be pregnant.

For males:

Erivedge is present in semen. Males should not donate semen while they are taking Erivedge and for 3 months after their final dose.
Male patients should always use a condom, even if they have had a vasectomy, during sex with female partners who are pregnant or who are able to become pregnant during treatment with Erivedge and for 3 months after their final dose to protect their female partner from being exposed to Erivedge.
Male patients must tell their healthcare provider right away if their partner becomes pregnant or thinks she is pregnant while they are taking Erivedge.

Exposure to Erivedge during pregnancy:

If a patient thinks that he or his female partner may have been exposed to Erivedge during pregnancy, they must talk to their healthcare provider right away. If a patient becomes pregnant during treatment with Erivedge, she or her healthcare provider should report the pregnancy to Genentech at (888) 835-2555.

Before taking Erivedge, patients should tell their healthcare provider:

If they are pregnant or plan to become pregnant
If they are breastfeeding or plan to breastfeed. It is not known if Erivedge passes into breast milk. Patients should not breastfeed during treatment and for 24 months after their final dose of Erivedge. Patients should talk with their healthcare provider about the best way to feed their baby during this time.
About all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements

While taking Erivedge, patients should avoid:

Patients should not donate blood or blood products while they are taking Erivedge and for 24 months after their final dose.
Patients should not donate semen while taking Erivedge and for 3 months after their final dose.

Possible Side Effects of Erivedge

Bone growth problems. Bone growth problems have happened in children who have been exposed to Erivedge. These problems may continue even after stopping treatment with 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, joint pain and vomiting.

Erivedge can cause absence of menstrual periods (amenorrhea) in females who are able to become pregnant. It is not known if amenorrhea is permanent. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all of the possible side effects of Erivedge. Because everyone is different, it is not possible to predict what side effects any one person will have or how severe they may be. Patients should talk to their doctor for medical advice about side effects.

Side effects may be reported to the FDA at (800) FDA-1088 or or www.fda.gov/medwatch. Side effects may also be reported to Genentech at (888) 835-2555.

Patients should read the full Prescribing Information for additional Important Safety Information, including serious side effects, and the Medication Guide.