Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`NDA 21-430
`NDA 20-785/S-031
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`
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`Celgene Corporation
`86 Morris Avenue
`Summit, NJ 07901
`
`Attention: Megan Parsi
`
`
`Director, Regulatory Affairs
`
`
`
`Dear Ms. Parsi:
`
`Please refer to your new drug application (NDA) dated December 22, 2003, received December 23,
`2003, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Thalomid®
`(thalidomide) capsules, 50 mg, 100 mg, and 200 mg.
`
`We acknowledge receipt of your submissions dated May 13, 2005; August 17, 2005; October 13 and
`25, 2005. The May 13, 2005 submission constituted a complete response to our October 22, 2004
`action letter.
`
`We also acknowledge receipt of your submission dated November 1, 2005, which was not reviewed
`for our November 10, 2005 action letter.
`
`We acknowledge receipt of your submission dated November 23, 2005, received November 25, 2005,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Thalomid®
`(thalidomide) capsules 50 mg, 100 mg, and 200 mg. The November 23, 2005 submission constitutes a
`complete response to our November 10, 2005 action letter.
`
`We further acknowledge receipt of your submissions dated November 17 and December 7, 2005;
`February 2 and 17, 2006; and March 14 and 16, 2006; May 10, May 11, May 15, May 16 and May 19,
`2006.
`
`Finally, we acknowledge your December 5, 2005 submission to NDA 20-785/S-031 which includes
`comparable labeling revisions to the parent NDA. This submission constitutes a complete response to
`the November 23, 2005 action letter.
`
`New drug application 21-430 provides for the use of Thalomid® (thalidomide) capsules, 50 mg, 100
`mg, and 200 mg for the treatment of patients with newly diagnosed multiple myeloma.
`
`We have completed our review of these applications, as amended. They are approved under the
`provisions of accelerated approval regulations (21 CFR 314.510 and 314.520), effective on the date of
`this letter, for use as recommended in the agreed upon labeling text and required patient labeling.
`
`Page 1 of 4
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`CELGENE EXHIBIT 2010
`Coalition for Affordable Drugs VI LLC (Petitioner) v. Celgene Corporation (Patent Owner)
`Case IPR2015-01102
`
`

`
`NDA 21-430
`NDA 20-785/S-031
`Page 2
`
`Marketing of this drug product and related activities must adhere to the substance and procedures of
`the referenced accelerated approval regulations.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling text and required patient
`labeling. Marketing the product with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
`
`Please submit an electronic version of the FPL according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Format - NDA. 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. Individually mount 15
`of the copies on heavy-weight paper or similar material. For administrative purposes, designate these
`individual submissions “FPL for approved NDA 21-430 and NDA 20-785/S-031.” Approval of these
`submissions by FDA is not required before the labeling is used.
`
`Products approved under the accelerated approval regulations 21 CFR 314.510 require further studies
`to verify and describe their clinical benefit. We remind you of your post marketing study
`commitments specified in your submission dated May 11, 2006. These commitments, along with any
`completion dates agreed upon, are listed below.
`
`A. Submit the clinical study report for THAL-MM-003, A Randomized Phase III Trial of
`Thalidomide Plus Dexamethasone Versus Dexamethasone in Newly Diagnosed Multiple Myeloma,
`as noted below:
`
`
`
`
`Protocol Submission:
`
`Study Start:
`
`Final Report Submission:
`
`B. Conduct an epidemiologic study (An Epidemiology Study of Venous Thrombotic Events in
`Thalidomide Treated Multiple Myeloma Patients) to address the questions detailed below:
`
`July 11, 2002 (Submitted as SPA to IND 49,481, Serial #070)
`March 13, 2003
`July 2007
`
`Safety questions
`1. What is the failure rate for each of the different types of thromboembolic prophylaxis (e.g.,
`antiplatelet or anticoagulant therapy) for MM patients treated with a thalidomide-containing
`regimen?
`2. What is the failure rate for each type of DVT treatment (dose-adjusted heparin, low molecular
`weight heparin, coumadin) for those patients with MM and a DVT who continue to receive
`ongoing treatment with thalidomide?
`3. What is the failure rate for each type of post-DVT thromboembolic prophylaxis for those
`patients with MM and a DVT who continue to receive ongoing treatment with thalidomide?
`
`This prospective epidemiologic study will enroll select patients identified in the S.T.E.P.S.
`program, and collect the necessary additional data on these patients to further evaluate
`occurrences of thrombosis and anticoagulant use. The final details of the design will be as
`agreed between the Agency and Celgene. The dates for submission of the protocol, study start
`date and final report submission are indicated below:
`
`
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`Page 2 of 4
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`

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`NDA 21-430
`NDA 20-785/S-031
`Page 3
`
`
`October 2006
`Protocol Submission:
`March 2007
`Study Start:
`
`Final Report Submission: March 2010
`
`Submit clinical protocols to your IND for this product. Submit nonclinical and chemistry,
`manufacturing, and controls protocols and all final study reports to NDA 20-785. For administrative
`purposes, all submissions relating to this postmarketing study commitment must be clearly designated
`"Subpart H-Postmarketing Study Commitment.” 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 Commitment
`Protocol”, “Postmarketing Study Commitment Final Report”, or “Postmarketing Study
`Commitment Correspondence.”
`
`Immediately submit all promotional materials (both promotional labeling and advertisements) to be
`used within the first 120 days after approval. Send one copy to the Division of Drug Oncology
`Products and two copies of the promotional materials and the package insert directly to:
`
`
`Food and Drug Administration
`
`
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`Food and Drug Administration
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81). With the approval of administrative NDA 21-430, this NDA number will be
`retired. All 15-day alert reports, periodic (including quarterly) adverse drug experience reports, field
`alerts, annual reports, supplements, and other submissions should be addressed to the original NDA
`20-785 for this drug product, not to this NDA. In the future, no submissions should be made to NDA
`21-430, except for the final printed labeling requested above.
`
`If you have any questions, call Carl Huntley, Regulatory Project Manager, at (301) 796-1372.
`
`Sincerely,
`{See appended electronic signature page}
`
`
`
`Renata Albrecht, M.D.
`
`
`Division Director
`
`
`Division of Special Pathogen
`
`and Transplant Products
`
`
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
`
`Enclosure: Labeling
`
`Robert L. Justice, M.D.
`Acting Division Director
`Division of Drug Oncology Products
`Office of Oncology Drug Products
`Center for Drug Evaluation and Research
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`Page 3 of 4
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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/
`---------------------
`Renata Albrecht
`5/25/2006 03:36:31 PM
`
`Robert Justice
`5/25/2006 04:17:45 PM
`
`Page 4 of 4