Pivotal Trial Results Pivotal Trial Results

ERIVANCE: The pivotal trial that demonstrated clinically meaningful benefit in advanced BCC

Study design: ERIVANCE was a Phase II, international, single-arm, 2-cohort, open-label trial 1,3

Conducted in 104 patients with either metastatic BCC (n=33) or locally advanced BCC (n=71).

Of the 104 patients enrolled, 96 patients were evaluable for objective response rate (ORR).

  • Patients were seen at baseline and every 4 weeks for safety monitoring
  • Patients were seen at baseline and every 8 weeks for response assessment

Primary efficacy outcome measures 1

ORR as assessed by an Independent Review Facility. See assessment criteria below for locally advanced BCC and metastatic BCC cohorts.

Baseline characteristics of evaluable patients 1,3

21% of patients had a preexisting diagnosis of Gorlin syndrome and met the inclusion criteria for advanced BCC.
*May not have been directed at target lesions.

Assessment of objective response in locally advanced BCC 1,3

A composite endpoint used to assess response

Objective response required the absence of disease progression and ≥1 of the following:

Assessment of objective response in metastatic BCC 1,3

Response is confirmed if present on 2 consecutive radiographic scans ≥4 weeks apart

Erivedge reduced disease burden as assessed visibly and histologically1-3

ERIVANCE trial: Visible lesion reduction was achieved in 43% of locally advanced BCC patients1

ORR=objective response rate.

Patients received at least 1 dose of Erivedge with independent pathologist-confirmed diagnosis of BCC. Locally advanced BCC patients were considered responders if they did not experience progression and had ≥30% reduction in lesion size (sum of the longest diameter) from baseline in target lesions by radiography or in externally visible dimensions of target lesions (scar tissue was measured); or had complete resolution of ulceration in all target lesions. Complete response was objective response with no residual BCC on sampling biopsy. Partial response was objective response with presence of residual BCC on sampling biopsy.

CI=confidence interval; ORR=objective response rate.

  • Scar tissue was measured as part of the lesion when assessing response, as specified in the study protocol
  • Independent Review evaluation of response included measurement of externally assessable tumor (including scar) and assessment for ulceration in photographs, radiographic assessment of target lesions (if appropriate), and biopsy
  • Median duration of response was 7.6 months (range, 1.0 to 12.9 months; 95% CI, 5.7–9.7)
    • 13 of 27 responding patients were no longer considered responders due to an event (disease progression or death)

Erivedge reduced disease burden as assessed radiographically 1-3

Erivedge was the first FDA-approved therapy for metastatic BCC

Patients received at least 1 dose of Erivedge with independent pathologist-confirmed diagnosis of BCC. In the metastatic BCC cohort, response was assessed according to RECIST version 1.0. Complete response was disappearance of all target and nontarget lesions. Partial response was ≥30% decrease in SLD of target lesions from baseline.

CI=confidence interval; ORR=objective response rate; RECIST=Response Evaluation Criteria in Solid Tumors; SLD=sum of the longest diameter.

  • Median duration of response was 7.6 months (range, 2.1 to 11.1 months; 95% CI, 5.6–not estimable)
    • 3 of 10 responding patients were no longer considered responders due to an event (disease progression or death)

Select Important Safety Information:

Erivedge can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. The Erivedge label contains Warnings and Precautions about Blood Donation, Semen Donation, and Premature Fusion of the Epiphyses. Please see additional information about all of these warnings and precautions below.

Erivedge adverse events: Help your patients know what to expect

Most common adverse events (incidence ≥ 10%) associated with Erivedge: Pooled analysis of 4 studies 1,2,4

Adverse reactions reported using Medical Dictionary for Regulatory Activities preferred terms and graded using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 for assessment of toxicity.

N/A=not applicable, this grade does not exist for this adverse reaction.

  • Amenorrhea can occur in females of reproductive potential. Reversibility of amenorrhea is unknown. In clinical trials, a total of 3 of 10 pre-menopausal women developed amenorrhea while receiving Erivedge 1
  • Treatment-emergent Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia in 6 patients (4%), hypokalemia in 2 patients (1%), and azotemia in 3 patients (2%) 1
  • Additionally, in a post-approval clinical trial conducted in 1232 patients with locally advanced or metastatic BCC treated with Erivedge, a subset of 29 patients had baseline values for CPK reported. Within the subset of patients, 38% had a shift from baseline, and one of the patients had a Grade 3 value. The prevalence of Grade 3/4 CPK elevation across the entire study population with any CPK measurement was 2.4% (11 out of 453 patients) 1

Important Safety Information and Indication

Indication

Erivedge® (vismodegib) capsule is indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Boxed Warning and Additional Important Safety Information

Embryo-Fetal Toxicity

  • Erivedge can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Erivedge is embryotoxic, fetotoxic, and teratogenic in animals. Teratogenic effects included severe midline defects, missing digits, and other irreversible malformations
  • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating Erivedge therapy. Advise females of reproductive potential to use effective contraception during and after Erivedge therapy. Advise males of the potential risk of Erivedge exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential. Advise pregnant women of the potential risks to a fetus
  • Advise female patients and female partners of male patients to contact their healthcare provider with a known or suspected pregnancy. Report pregnancies to Genentech at (888) 835‑2555

Female Patients

  • Advise females of reproductive potential to use effective contraception during therapy with Erivedge and for 24 months after the final dose

Male Patients

  • Advise males of the potential risk to an embryo or fetus if a female partner of reproductive potential is exposed to Erivedge. Advise male patients to use condoms with a pregnant partner or a female partner of reproductive potential, even after a vasectomy, during therapy and for 3 months after the final dose of Erivedge

Blood Donation

  • Advise patients not to donate blood or blood products while receiving Erivedge and for 24 months after the final dose of Erivedge

Semen Donation

  • Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm. Advise male patients not to donate semen during and for 3 months after the final dose of Erivedge

Premature Fusion of the Epiphyses

  • Premature fusion of the epiphyses has been reported in pediatric patients exposed to Erivedge. In some cases, fusion progressed after drug discontinuation

Adverse Reactions

  • The most common adverse reactions (≥10%) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia
  • Amenorrhea can occur in females of reproductive potential. Reversibility of amenorrhea is unknown. In clinical trials, a total of 3 of 10 pre-menopausal women developed amenorrhea while receiving Erivedge
  • Treatment-emergent Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia in 6 patients (4%), hypokalemia in 2 patients (1%), and azotemia in 3 patients (2%)
  • Additionally, in a post-approval clinical trial conducted in 1232 patients with locally advanced or metastatic BCC treated with Erivedge, a subset of 29 patients had baseline values for CPK reported. Within the subset of patients, 38% had a shift from baseline, and one of the patients had a Grade 3 value. The prevalence of Grade 3/4 CPK elevation across the entire study population with any CPK measurement was 2.4% (11 out of 453 patients)

Use in Specific Populations

Lactation

  • No data are available regarding the presence of vismodegib in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in breastfed infants from Erivedge, advise a nursing woman that breastfeeding is not recommended during therapy with Erivedge and for 24 months after the final dose

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see full Prescribing Information, including the BOXED WARNING and the Medication Guide, for a complete discussion of the risks associated with Erivedge.