DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
Silver Spring MD 20993

NDA 208692
NDA APPROVAL
Exelixis, Inc.
Attention: Lisa Sauer
Vice President, Regulatory Affairs
210 East Grand Avenue
South San Francisco, CA 94080

Dear Ms. Sauer:
Please refer to your New Drug Application (NDA) dated December 22, 2015, received
December 22, 2015, and your amendments, submitted under section 505(b) of the Federal Food,
Drug, and Cosmetic Act (FDCA) for CABOMETYX (cabozantinib) Tablets, 20 mg, 40 mg, and
60 mg.
We also refer to our approval letter dated April 25, 2016, which contained the following errors:
1.  Immediate container labels did not reflect the final agreed upon version. The statement
“Store in the original package” should not have been present on the approved label.
2.  Section 8.1 of the Full Prescribing Information, “Animal Data” subsection, contained an
error in the last sentence of the first paragraph, “Findings included delayed ossification
and skeletal variations at a dose of 0.1 mg/kg/day (approximately 0.04-fold of human
AUC at the recommended dose).” The 0.1 should be 0.01.
This replacement approval letter incorporates the correction of the errors. The effective approval
date will remain April 25, 2016, the date of the original approval letter.
This new drug application provides for the use of CABOMETYX (cabozantinib) Tablets for the
treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti­
angiogenic therapy.
We have completed our review of this application, as amended. It is approved, effective on the
date of this letter, for use as recommended in the enclosed agreed-upon labeling text. Please be
advised that a 36 month shelf life is granted for the drug product stored at 25°C (77°F),
excursions permitted to 15° to 30 °C (59° to 86°F).
CONTENT OF LABELING
As soon as possible, but no later than 14 days from the date of this letter, submit the content of
labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA

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automated drug registration and listing system (eLIST), as described at
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
of labeling must be identical to the enclosed labeling (text for the package insert, text for the
patient package insert). Information on submitting SPL files using eLIST may be found in the
guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM072392.pdf.
The SPL will be accessible via publicly available labeling repositories.
IMMEDIATE CONTAINER LABELS
Submit final printed immediate container labels that are identical to the immediate container
labels submitted on April 1, 2016, as soon as they are available, but no more than 30 days after
they are printed. Please submit these labels electronically according to the guidance for industry
Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product
Applications and Related Submissions Using the eCTD Specifications (June 2008).
Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
heavy-weight paper or similar material. For administrative purposes, designate this submission
“Final Printed Container Labels for approved NDA 208692.” Approval of this submission
by FDA is not required before the labeling is used.
Marketing the product(s) with FPL that is not identical to the approved labeling text may render
the product misbranded and an unapproved new drug.
REQUIRED PEDIATRIC ASSESSMENTS
Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
administration are required to contain an assessment of the safety and effectiveness of the
product for the claimed indication(s) in pediatric patients unless this requirement is waived,
deferred, or inapplicable.
We are waiving the pediatric studies requirement for this application because necessary studies
are impossible or highly impracticable since renal cell carcinoma does not occur in children.
POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
UNDER SECTION 506B
We remind you of your postmarketing commitment:
3063-1 

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Combine all available pharmacokinetics (PK) data from different patient
populations and healthy subjects in an integrated population PK model to evaluate
the potential impact of tumor types on the PK of cabozantinib.

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The timetable you submitted on April 7, 2016, states that you will conduct this study according
to the following schedule:
Final Report Submission:

06/16

Submit clinical protocols to your IND 072596 for this product. Submit nonclinical and
chemistry, manufacturing, and controls protocols and all postmarketing final reports to this
NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii) you should include a
status summary of each commitment in your annual report to this NDA. The status summary
should include expected summary completion and final report submission dates, any changes in
plans since the last annual report, and, for clinical studies/trials, number of patients entered into
each study/trial. All submissions, including supplements, relating to these postmarketing
commitments should be prominently labeled “Postmarketing Commitment Protocol,”
“Postmarketing Commitment Final Report,” or “Postmarketing Commitment
Correspondence.”
PROMOTIONAL MATERIALS
You may request advisory comments on proposed introductory advertising and promotional
labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
proposed materials in draft or mock-up form with annotated references, and the package insert,
Medication Guide, and patient PI (as applicable) to:
OPDP Regulatory Project Manager

Food and Drug Administration 

Center for Drug Evaluation and Research

Office of Prescription Drug Promotion

5901-B Ammendale Road

Beltsville, MD 20705-1266

Alternatively, you may submit a request for advisory comments electronically in eCTD format.
For more information about submitting promotional materials in eCTD format, see the draft
Guidance for Industry (available at:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM443702.pdf ).
As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
2253. Form FDA 2253 is available at
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
Information and Instructions for completing the form can be found at
http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
more information about submission of promotional materials to the Office of Prescription Drug
Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.

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REPORTING REQUIREMENTS
We remind you that you must comply with reporting requirements for an approved NDA
(21 CFR 314.80 and 314.81).
If you have any questions, contact Rajesh Venugopal, Senior Regulatory Project Manager, at
(301) 796-4730.
Sincerely,
{See appended electronic signature page}
Geoffrey Kim, MD
Director
Division of Oncology Products 1
Office of Hematology and Oncology Products
Center for Drug Evaluation and Research

Enclosure(s):
Content of Labeling
Immediate Container Labeling

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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.
--------------------------------------------------------------------------------------------------------/s/
---------------------------------------------------GEOFFREY S KIM
04/25/2016

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