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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 21-756
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`Eyetech Pharmaceuticals, Inc.
`Attention: Loni da Silva
`Vice President, Global Regulatory Affairs
`Three Times Square
`12th Floor
`New York, New York 10036
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`
`Dear Ms. da Silva:
`
`Please refer to your new drug application (NDA) dated June 17, 2004, received June 17, 2004,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Macugen (pegaptanib
`sodium injection) 0.3 mg.
`
`We acknowledge receipt of your submissions dated March 17, May 12 and 27, June 7, July 14 and 28,
`September 10, 13, 20, 22, 23, and 30, October 4, 5, 7, 15, and 29, November 10 (three), 12, 19, 22, and
`23, and December 1, 6, 8, 10 (three), 13, 14 and 16, 2004.
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`This new drug application provides for the use of Macugen (pegaptanib sodium injection) for the
`treatment of neovascular (wet) age-related macular degeneration.
`
`We completed our review of this application, as amended. It is approved, effective on the date of this
`letter, for use as recommended in the agreed-upon labeling text.
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`The final printed labeling (FPL) must be identical to the enclosed draft labeling (package insert
`submitted December 10, 2004, carton and container labeling submitted December 16, 2004).
`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
`
`The electronic labeling rule published December 11, 2003, (68 FR 69009) requires submission of
`labeling content in electronic format effective June 8, 2004. For additional information, consult the
`following guidances for industry regarding electronic submissions: Providing Regulatory
`Submissions in Electronic Format - NDAs (January 1999) and Providing Regulatory Submissions in
`Electronic Format – Content of Labeling (February 2004). The guidances specify that labeling is to
`be submitted in pdf format. To assist in our review, we request that labeling also be submitted in MS
`Word format. If formatted copies of all labeling pieces (i.e., package insert, container labels, and
`carton labels) are submitted electronically, labeling does not need to be submitted in paper.
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`Exhibit 2117
`Page 01 of 04
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`

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`NDA 21-756
`Page 2
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`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. We are
`waiving the pediatric study requirement for this application.
`
`We remind you of your postmarketing study commitments in your submission dated
`December 10, 2004. These commitments are listed below.
`
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`1. Provide clinical information from a 2-year (minimum) clinical study to support that there
`are no degenerative effects on the neurosensory retina following the intravitreal
`administration of Macugen.
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`
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`by June, 2005
`by January, 2007
`by July, 2009
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`Protocol Submission:
`Study Start:
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`Final Report Submission:
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`2. Provide clinical information from a 1-year (minimum) clinical study to support that there
`are no adverse effects on the corneal endothelium following the intravitreal administration
`of Macugen.
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`Protocol Submission:
`Study Start:
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`Final Report Submission:
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`by June, 2005
`by January, 2007
`by July, 2008
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`3. Provide safety and efficacy data from a 2-year (minimum) clinical study of at least two
`additional doses of Macugen below 0.3 mg.
`
`by June, 2005
`by January, 2007
`by July, 2009
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`Protocol Submission:
`Study Start:
`
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`Final Report Submission:
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`Submit clinical protocols to your IND for this product. 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
`postmarketing study commitments must be prominently labeled “Postmarketing Study Protocol”,
`“Postmarketing Study Final Report”, or “Postmarketing Study Correspondence.”
`
`(b)(4)
`We remind you of the agreement in your December 10, 2004, submission to
`(b)(4)
` by March, 2006.
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`Exhibit 2117
`Page 02 of 04
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`

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`NDA 21-756
`Page 3
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`We acknowledge the following agreements from our December 17, 2004, teleconference:
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`
`(b)(4)
`a) Provide data by January 14, 2005, to show that the is
`sufficiently low.
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`Division of Drug Marketing, Advertising,
`and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, MD 20857
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`b) Provide initial materials by December 31, 2004, to educate medical providers of the controlled
`aseptic conditions under which the drug product must be administered in order to reduce risk to
`the patient and coordinate with the Division for all subsequent educational materials.
`
`(b)(4)
`c) Provide continued
`
`In addition, submit three copies of the introductory promotional and educational materials that you
`propose to use for this product. Submit all proposed materials in draft or mock-up form, not final
`print. Send one copy to the Division of Anti-Inflammatory, Analgesic, and Ophthalmic Drug Products,
`and two copies of both the promotional materials and the package insert directly to:
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`Please submit one market package of the drug product when it is available.
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`We have not completed validation of the regulatory methods. However, we expect your continued
`cooperation to resolve any problems that may be identified.
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81).
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`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse event
`reports that are received directly by the FDA. New molecular entities and important new biologics
`qualify for inclusion for three years after approval. Your firm is eligible to receive copies of reports for
`this product. To participate in the program, please see the enrollment instructions and program
`description details at www.fda.gov/medwatch/report/mmp.htm.
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`If you have any questions, contact Michael Puglisi, Project Manager, at (301) 827-2090.
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`Enclosure
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`Sincerely,
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`{See appended electronic signature page}
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`Jonca C. Bull, M.D.
`Director
`Office of Drug Evaluation V
`Center for Drug Evaluation and Research
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`Exhibit 2117
`Page 03 of 04
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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/
`---------------------
`Jonca Bull
`12/17/04 06:57:56 PM
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`Exhibit 2117
`Page 04 of 04
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