Erivedge® (vismodegib) pivotal trial results  Erivedge® (vismodegib) 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 3,4

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
Erivedge® (vismodegib) pivotal trial study callout Erivedge® (vismodegib) pivotal trial study callout

Primary efficacy outcome measures 3

ORR as assessed by independent review. See assessment criteria below for locally advanced BCC and metastatic BCC cohorts.

Baseline characteristics of evaluable patients 3,4

 Erivedge® (vismodegib) pivotal trial demographic and baseline characteristics  Erivedge® (vismodegib) pivotal trial demographic and baseline characteristics

21% of patients had a preexisting diagnosis of Gorlin syndrome and met the inclusion criteria for advanced BCC.

Assessment of objective response in locally advanced BCC 3,4

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 3,4

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

Erivedge reduced disease burden visibly and histologically 3,4

Erivedge® (vismodegib) pivotal trial primary endpoint chart Erivedge® (vismodegib) pivotal trial primary endpoint chart

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 of response included measurement of externally assessable tumor (including scar) and assessment for ulceration in photographs, radiographic assessment of target lesions (if appropriate), and tumor 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) 1

Erivedge reduced disease burden radiographically 3,4

Erivedge was the first FDA-approved therapy for metastatic BCC 2

 Erivedge® (vismodegib) pivotal trial mBCC chart  Erivedge® (vismodegib) pivotal trial mBCC chart

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) 1

Select Important Safety Information:

Erivedge has Boxed Warnings for embryo-fetal toxicity, which can cause deaths or severe birth defects. Advise females of reproductive risks prior to initiating Erivedge. Advise males of potential risks through semen and to use condoms with a female partner of reproductive potential. Please see additional information about all of these warnings and precautions below.

Erivedge adverse reactions: Help your patients know what to expect

Most common adverse reactions (incidence ≥10%) associated with Erivedge: Pooled analysis of 4 studies 1,3,5

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, 30% of 10 pre-menopausal women developed amenorrhea while receiving Erivedge
  • Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia (4%), azotemia (2%), and hypokalemia (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 blood creatine phosphokinase (CPK) reported. Within the subset of patients, 38% had a shift from baseline, including Grade 3 (3%) increased CPK. Grade 3 or 4 increased CPK occurred in 2.4% of the 453 patients across the entire study population with any CPK measurement
  • Twenty-nine patients (28%) experienced adverse reactions that led to treatment interruption

Important Safety Information and Indication

Indication

Erivedge 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

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 the pregnancy status of females of reproductive potential within 7 days prior to initiating Erivedge. Advise pregnant women of the potential risks to a fetus. Advise females of reproductive potential to use effective contraception during and after Erivedge
  • 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
  • Females of Reproductive Potential: Use contraception during therapy with Erivedge and for 24 months after the final dose
  • Males: Use condoms, even after a vasectomy, to avoid potential drug exposure in pregnant partners and female partners of reproductive potential during and for 3 months after the final dose of Erivedge. Do not donate semen during 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
  • 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

Additional Important Safety Information

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. Erivedge is not indicated for pediatric patients

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, 30% of 10 pre-menopausal women developed amenorrhea while receiving Erivedge
  • Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia (4%), azotemia (2%), and hypokalemia (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 blood creatine phosphokinase (CPK) reported. Within the subset of patients, 38% had a shift from baseline, including Grade 3 (3%) increased CPK. Grade 3 or 4 increased CPK occurred in 2.4% of the 453 patients across the entire study population with any CPK measurement

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 child, or the effects of the drug on milk production. Advise women 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.