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
---------------------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
MICHELLE L SAFARIK
09/25/2012
AMY TOSCANO
09/25/2012
Reference ID: 3194707

Posted: September 2012


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