Genentech Submits New Drug Application to FDA
Genentech has announced that it has submitted a New Drug
Application for vismodegib to the FDA for the treatment of people
with advanced basal cell carcinoma (BCC) when surgery is
no longer an option. Vismodegib is taken orally and designed
to selectively inhibit signaling in the Hedgehog pathway, which
is implicated in more than 90 percent of BCC cases. BCC is
the most common type of skin cancer, and is generally considered
curable by surgery. However, advanced BCC can cause
disfiguring and debilitating effects and can ultimately be lifethreatening.
This submission to the FDA is based on results from the ERIVANCE
BCC study that evaluated vismodegib in people with
advanced BCC. ERIVANCE BCC is an international, singlearm,
multicenter, two-cohort, open-label Phase 2 study that
enrolled 104 patients with advanced BCC, including locally
advanced BCC (laBCC) (71) and metastatic BCC (mBCC) (33).
laBCC patients had lesions that were inappropriate for surgery
(inoperable or for whom surgery would result in substantial
deformity) and for which radiotherapy was unsuccessful or
contraindicated. mBCC was defined as BCC that had spread
to other parts of the body, including the lymph nodes, lungs,
bones and/or internal organs. Study participants received 150
mg vismodegib orally, once daily until disease progression or
intolerable toxicity.
The trial showed vismodegib substantially shrank tumors or
healed visible lesions in 43 percent of patients with laBCC and
30 percent of patients with mBCC, as assessed by independent
review, the primary endpoint of the study. The ORR as assessed
by study investigators, a secondary endpoint, was 60 percent
for laBCC and 46 percent for mBCC. The median duration of
progression-free survival (PFS) by independent review for both
metastatic and locally advanced BCC patients was 9.5 months
The most common drug-related adverse events were muscle
spasms, hair loss, altered taste sensation, weight loss, fatigue,
nausea, decreased appetite and diarrhea. Serious adverse
events were observed in 25 percent of the study patients,
but only four percent of patients had serious adverse events
that were considered by the researchers to be related to vismodegib,
including one case each of blocked bile flow from
the liver (cholestasis), dehydration with loss of consciousness
(syncope), pneumonia accompanied by an inability of the heart
to pump enough blood (cardiac failure), and a sudden arterial
blockage in the lung (pulmonary embolism).
FDA Gives Provisional Approval to MelaFind Device
Mela Sciences has announced that the FDA has deemed its
noninvasive melanoma detection device, MelaFind, approvable.
MelaFind is a multispectral computer vision system with
a handheld imager that captures the image of a lesion; software
uses algorithms to analyze the image, indicating within
two minutes whether a biopsy should be done. Mela Sciences´
application relied on a trial of MelaFind that included 1,383
patients and showed a sensitivity of 98 percent. According to
Mela Sciences, the device´s sensitivity rating for malignant melanoma
was better than that of dermatologists, who showed a
wide range of variability about which lesions would have been
recommended for biopsy and which relegated to observation.
The FDA´s provisional approval follows a May 2011 Citizen Petition
filed by Mela Sciences with the FDA seeking action on its
application for approval. An FDA advisory panel, in November
2010, had voted eight to seven with one abstention on Mela
Sciences´ initial approval.
Members of the FDA advisory panel had expressed concern
that the MelaFind device might be used by non-dermatologists
or that it would be used in place of clinical evaluation. As a
result, Mela Sciences will have to work with the FDA on physician
and patient labeling, a package insert and user´s guide,
a training program for dermatologists, and the protocol for a
post-marketing study.
The indications for use state that the MelaFind "is intended for
use on clinically atypical cutaneous pigmented lesions with one
or more clinical or historical characteristics of melanoma, excluding
those with a clinical diagnosis of melanoma or likely
melanoma." In addition, the product labeling will also state that
the device is "only for use by physicians trained in the clinical
diagnosis and management of skin cancer (i.e., dermatologists)
who have also successfully completed a training program in
the appropriate use of MelaFind."
Mela Sciences has stated that it expects MelaFind to be commercially
available in the spring of 2012 to a select group of
dermatologists in Connecticut, New Jersey, and New York as a trial
run before making it available to a larger number of practices.
