FDA Sends Endo Letter for 'Misleading' Vantas Brochure
SILVER SPRING, Md., Sept. 25, 2012 - The FDA has
posted on its web site a letter about its review of
Endo Pharmaceuticals' Caregiver Brochure
for Vantas (histrelin acetate) subcutaneous implant. According
to the agency, the brochure is misleading because it omits serious
risk information for Vantas.
Promotional Material
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health
Service
Food and Drug Administration
Silver Spring, MD 20993
Mark Klinger
Associate Director, Regulatory Affairs
Endo Pharmaceuticals Inc.
100 Endo Boulevard
Chadds Ford, PA 19317
RE: NDA #021732
VANTAS
®
(histrelin acetate) subcutaneous implant
MA #123
Dear Mr. Klinger:
The Office of Prescription Drug Promotion (OPDP), Division of
Consumer Drug Promotion
(DCDP) of the U.S. Food and Drug Administration (FDA) has reviewed
a Caregiver Brochure
(VN-01094b) (brochure) for VANTAS
®
(histrelin acetate) subcutaneous implant (Vantas)
submitted by Endo Pharmaceuticals Inc. (Endo) under cover of Form
FDA-2253. The
brochure is misleading because it omits serious risk information
for Vantas. Thus, the
brochure misbrands the drug in violation of the Federal Food, Drug,
and Cosmetic Act (FD&C
Act), 21 U.S.C. 352(a) and 321(n). 21 CFR
1.21.
Background
Below is the indication and summary of the most serious and most
common risks associated
with the use of Vantas.
1
According to the FDA-approved product labeling (PI), Vantas is
indicated for the palliative
treatment of advanced prostate cancer.
Vantas is associated with several serious risks. According to
the PI, Vantas is
contraindicated in patients with hypersensitivity to gonadotropin
releasing hormone (GnRH),
GnRH agonist analogs, or any of the components in the drug since
anaphylactic reactions to
synthetic GnRH agonist analogs have been reported in the
literature. Vantas is also
contraindicated in women who are or who may become pregnant, as it
can cause fetal
harm.
Vantas has warnings and precautions regarding the onset of new or
worsening symptoms
due to a transient increase in serum concentrations of testosterone
during the first week of
treatment; spinal cord compression (which may result in paralysis)
and ureteral obstruction
1
This information is for background purposes only and does not
necessarily represent the risk information that
should be included in the promotional piece cited in this
letter.
Reference ID: 3194707
Mark Klinger Page 2
Endo Pharmaceuticals Inc.
NDA #021732/MA #123
(which may cause renal impairment); difficulty in locating or
removing the implant;
hyperglycemia and increased risk of developing diabetes mellitus;
increased risk of
developing myocardial infarction, sudden cardiac death, and stroke;
and periodic monitoring
of serum concentrations of testosterone and prostate-specific
antigen to assess response to
the drug.
The most common adverse reactions that occurred with Vantas therapy
in >5% of men were
hot flashes, fatigue, implant site reaction, and testicular
atrophy.
Omission of Risk Information
Promotional materials are misleading if they fail to reveal facts
that are material in light of the
representations made by the materials or with respect to
consequences that may result from
the use of the drug as recommended or suggested by the
materials.
The brochure contains several claims discussing the efficacy and
dosing regimen benefits of
Vantas. For example,
• “One kind of ADT [androgen
deprivation therapy] is a gonadotropin releasing
hormone (GnRH) agonist, which works by decreasing the amount
of
testosterone that the body makes. This decrease in
testosterone can slow the
growth of prostate cancer cells.
“VANTAS
®
is one type of GnRH agonist that may help relieve the
symptoms of
prostate cancer; it is not a cure. It is implanted into the
arm and is designed to
continuously deliver drug every day for 12 months. Because of
its once-yearly
administration, VANTAS may mean fewer interruptions to your loved
one’s life,
and possibly yours.” (page six)
• “VANTAS
®
(histrelin acetate) subcutaneous implant is a once-yearly
hormone
suppression therapy for prostate cancer. Hormone therapies
like VANTAS may
help relieve the symptoms of advanced prostate cancer, but are not
a cure.
VANTAS is different from multiple injection therapies because with
one implant
per year, your loved one continuously receives 12 months of
medicine. This
may mean less interruptions to his life and less time spent at
doctor
appointments specifically for the administration of a GnRH
agonist. Fewer
treatment administrations may mean less time in a doctor’s
office for you too.”
(page 10)
However, the brochure fails to state that paralysis may result from
the risk of spinal cord
compression, and that patients are at increased risk of developing
hyperglycemia, diabetes
mellitus, myocardial infarction, sudden cardiac death, and
stroke. As a result, the brochure
misleadingly suggests that Vantas is safer than has been
demonstrated.
Reference ID: 3194707
Mark Klinger Page 3
Endo Pharmaceuticals Inc.
NDA #021732/MA #123
Conclusion and Requested Action
For the reasons described above, the brochure misbrands Vantas in
violation of the FD&C
Act, 21 U.S.C. 352(a) and 321(n). 21 CFR
1.21.
OPDP requests that Endo immediately cease the dissemination of
violative promotional
materials for Vantas such as those described above. Please
submit a written response to
this letter on or before October 10, 2012, stating whether you
intend to comply with this
request, listing all promotional materials (with the 2253
submission date) for Vantas that
contain violations such as those described above, and explaining
your plan for discontinuing
use of such violative materials.
Please direct your response to the undersigned at the Food and Drug
Administration,
Center for Drug Evaluation and Research, Office of Prescription
Drug Promotion,
Division of Consumer Drug Promotion, 5901-B Ammendale Road,
Beltsville, Maryland
20705-1266 or by facsimile at (301) 847-8444. Please note
that the Division of Drug
Marketing, Advertising, and Communications (DDMAC) has been
reorganized and elevated
to OPDP. OPDP consists of the Immediate Office, the Division
of Professional Drug
Promotion (DPDP), and DCDP. To ensure timely delivery of your
submissions, please use
the full address above and include a prominent directional notation
(e.g., a sticker) to indicate
that the submission is intended for OPDP. In addition, OPDP
recently migrated to a different
tracking system. Therefore, OPDP letters will now refer to MA
numbers instead of MACMIS
numbers. Please refer to MA #123 in addition to the NDA
number in all future
correspondence relating to this particular matter. OPDP
reminds you that only written
communications are considered official.
The violations discussed in this letter do not necessarily
constitute an exhaustive list. It is
your responsibility to ensure that your promotional materials for
Vantas comply with each
applicable requirement of the FD&C Act.
Sincerely,
{See appended electronic signature page}
Michelle Safarik, MSPAS, PA-C
Regulatory Review Officer
Division of Consumer Drug Promotion
Office of Prescription Drug Promotion
{See appended electronic signature page}
Amy Toscano, PharmD, CPA
Team Leader
Division of Consumer Drug Promotion
Office of Prescription Drug Promotion
Reference ID: 3194707
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This is a representation of an electronic record that was
signed
electronically and this page is the manifestation of the
electronic
signature.
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/s/
----------------------------------------------------
MICHELLE L SAFARIK
09/25/2012
AMY TOSCANO
09/25/2012
Reference ID: 3194707
Posted: September 2012
