DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Food and Drug Administration
`Rockville MD 20857
`
`NDA 20-896/S-010, S-011
`
`Hoffman-LaRoche Inc
`340 Kingsland Street
`Nutley, NJ 07110-1199
`
`Attention: Murad Husain
`Program Director
`
`Dear Mr. Husain:
`
`Please refer to your supplemental new drug application dated March 7, 2001, received March 8, 2001,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Xeloda (capcitabine)
`Tablets.
`
`We acknowledge receipt of your submissions dated March 28, April 18, May 14 and 25, June 7, 11, 21, and
`28, and August 30, 2001.
`
`This supplemental new drug application provides for the use of Xeloda (capcitabine) Tablets in combination
`with Taxotere (docetaxel) for the treatment of patients with locally advanced or metastatic breast cancer after
`failure of prior anthracycline containing chemotherapy.
`
`Additionally, we acknowledge receipt of your July 27, 2001 warfarin labeling supplement #011.
`
`We have completed the review of these supplemental applications, as amended, and have concluded that
`adequate information has been presented to demonstrate that the drug product is safe and effective for use as
`recommended in the agreed upon enclosed labeling text. Accordingly, these supplemental applications are
`approved effective on the date of this letter.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert, text for
`the patient package insert).
`
`Please submit the copies of final printed labeling (FPL) electronically according to the guidance for industry
`titled Providing Regulatory Submissions in Electronic Format - NDA (January 1999). Alternatively, you
`may submit 20 paper copies of the FPL as soon as it is available but no more than 30 days after it is printed.
`Please individually mount ten of the copies on heavy-weight paper or similar material. For administrative
`purposes, this submission should be designated "FPL for approved supplement NDA 20-896/S-010 and S-
`011." Approval of this submission by FDA is not required before the labeling is used.
`
`This NDA was approved under the regulations for accelerated approval of new drugs for serious or life-
`threatening illnesses, specifically, 21 CFR 314.510. Approval of this supplement fulfills your commitments
`
`IMMUNOGEN 2214, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`NDA 20-896/ S-010, S-011
`Page 2
`
`made under 21 CFR 314.510.
`We remind you of your September 5, 2001 E-mail post-marketing study commitments listed below:
`
`1. A Phase 2, three-arm Randomized Study of Standard Dose Intermittent Oral Capecitabine (Q3W)
`versus "Low" Dose Intermittent Oral Capecitabine versus Alternate Dose and Schedule Intermittent
`Oral Capecitabine (Q4W) in Patients with Locally Advanced or Metastatic Breast Cancer.
`
`Protocol Submission:
`Study Start:
`Final Report Submission:
`
`December 2001 – January 2002
`March 2002
`December 2003
`
`2.
`
`Pharmacokinetic study of the combination of Xeloda plus docetaxel to determine if long term
`coadministration of capecitabine and docetaxel alters the pharmacokinetics of capecitabine,
`capecitabine's metabolites, docetaxel, or a combination of these moieties. The performance of the
`analytical methods and the reporting of the analytical methods for these data should be consistent with
`FDA's guidance: Bioanalytical Method Validation which is available at
`http://www.fda.gov/cder/guicance/index.htm.
`
`Protocol Submission:
`Study Start:
`Final Report Submission:
`
`December 2001
`March 2002
`December 2003
`
`Submit clinical protocols to your IND for this product. Submit nonclinical and chemistry, manufacturing, and
`controls protocols and all study 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, number of patients entered into each
`study. All submissions, including supplements, relating to these post-marketing study commitments must be
`prominently labeled "Postmarketing Study Protocol", "Post-marketing Study Final Report", or "Post-
`marketing Study Correspondence."
`
`Be advised that, as of April 1, 1999, all applications for new active ingredients, new dosage forms, new
`indications, new routes of administration, and new dosing regimens are required to contain an assessment of
`the safety and effectiveness of the product in pediatric patients unless this requirement is waived or deferred
`(63 FR 66632). We are waiving the pediatric study requirement for this action on this application.
`
`In addition, please submit three copies of the introductory promotional materials that you propose to use for
`this product. All proposed materials should be submitted in draft or mock-up form, not final
`
`IMMUNOGEN 2214, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`NDA 20-896/ S-010, S-011
`Page 3
`
`print. Please submit one copy to this Division and two copies of both the promotional materials and the
`package insert directly to:
`
`Division of Drug Marketing, Advertising, and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, Maryland 20857
`
`If a letter communicating important information about this drug product (i.e., a "Dear Health Care
`Professional" letter) is issued to physicians and others responsible for patient care, we request that you submit
`a copy of the letter to this NDA and a copy to the following address:
`
`MEDWATCH, HF-2
`FDA
`5600 Fishers Lane
`Rockville, MD 20857
`
`We remind you that you must comply with the requirements for an approved NDA set forth under
`21 CFR 314.80 and 314.81.
`
`If you have any questions, call Maureen Pelosi, Project Manager, at (301) 594-5778.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Richard Pazdur, M.D.
`Director
`Division of Oncology Drug Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`Enclosure
`
`IMMUNOGEN 2214, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`--------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`--------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Richard Pazdur
`9/7/01 04:41:32 PM
`
`
`
`IMMUNOGEN 2214, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`