DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Food and Drug Administration
`Rockville, MD 20857
`
`NDA 21-572
`
`Cubist Pharmaceuticals, Inc.
`Attention: David H. Schubert
`Vice President, Regulatory Affairs and Quality
`65 Hayden Avenue
`Lexington, MA 02421
`
`Dear Mr. Schubert:
`
`Please refer to your new drug application (NDA) dated December 19, 2002, received December 20,
`2002, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Cubicin™
`(daptomycin for injection) Intravenous Injection.
`
`We acknowledge receipt of your submissions dated January 23, February 4, March 12, 17 (2), 26, 27,
`and 31, April 7, 9, 11, 16, 21, and 22, May 8, 12, 14 (2), 15, 16, 19, 20, 28 (2), 29, and 30, June 16, 19,
`and 30, July 3, 15, 18, 23, and 30, August 5 (2), 7, and 8, September 3 (2), 10, 11, and 12, 2003.
`
`This new drug application provides for the use of Cubicin™ (daptomycin for injection) for the
`treatment of complicated skin and skin structure infections caused by susceptible strains of the
`following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant
`strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp.
`equisimilis and Enterococcus faecalis (vancomycin-susceptible strains only).
`
`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 agreed-upon labeling text.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert,
`immediate container and carton label). Marketing the product with FPL that is not identical to the
`approved labeling text may render the product misbranded and 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 this
`submission “FPL for approved NDA 21-572.” Approval of this submission by FDA is not required
`before the labeling is used.
`
`

`

`NDA 21-572
`Page 2
`
`We remind you of your postmarketing study commitment agreed to in your submission dated
`September 11, 2003. This commitment is listed below.
`
`COMMITMENT #1
`
`Description:
`
`Conduct a clinical study to assess the safety, efficacy, and
`pharmacokinetics of daptomycin in renal impairment patients (inclusive
`of patients with foot and decubitus ulcers complicated by diabetes) with
`complicated skin and skin structure infections. Enrollment into the study
`should be limited to patients with an estimated (via the Cockcroft and
`Gault equation using actual body weight) creatinine clearance ≤50
`mL/min and an attempt should be made to enroll an equal number of
`patients into the following categories: CLCR 30-50 mL/min, CLCR <30
`mL/min, hemodialysis patients, and CAPD patients.
`
`Protocol Submission:
`Study Start:
`Final Report:
`
`Within 3 months of this letter
`Within 6 months of this letter
`Within 24 months of this letter
`
`Submit clinical protocols to your IND for this product. Submit all study 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 postmarketing study commitments must be prominently labeled
`“Postmarketing Study Protocol”, “Postmarketing Study Final Report”, or “Postmarketing Study
`Correspondence.”
`
`As you pursue additional development of daptomycin, we strongly encourage you to investigate
`potential risk factors for development of muscle toxicity due to daptomycin. These could include
`effects of altered fluid/electrolyte and metabolic states (e.g., diabetes, thyroid disease, altered hormonal
`status).
`
`FDA's Pediatric Rule [at 21 CFR 314.55/21 CFR 601.27] was challenged in court. On October 17,
`2002, the court ruled that FDA did not have the authority to issue the Pediatric Rule and has barred
`FDA from enforcing it. Although the government decided not to pursue an appeal in the courts, it will
`work with Congress in an effort to enact legislation requiring pharmaceutical manufacturers to conduct
`appropriate pediatric clinical trials. In addition, third party interveners have decided to appeal the
`court's decision striking down the rule. Therefore, we encourage you to submit a pediatric plan that
`describes development of your product in the pediatric population where it may be used. Please be
`aware that whether or not this pediatric plan and subsequent submission of pediatric data will be
`required depends upon passage of legislation or the success of the third party appeal. In any event, we
`hope you will decide to submit a pediatric plan and conduct the appropriate pediatric studies to provide
`important information on the safe and effective use of this drug in the relevant pediatric populations.
`
`The pediatric exclusivity provisions of FDAMA as reauthorized by the Best Pharmaceuticals for
`Children Act are not affected by the court's ruling. Pediatric studies conducted under the terms of
`section 505A of the Federal Food, Drug, and Cosmetic Act may result in additional marketing
`exclusivity for certain products. You should refer to the Guidance for Industry on Qualifying for
`
`

`

`NDA 21-572
`Page 3
`
`Pediatric Exclusivity (available on our web site at www.fda.gov/cder/pediatric) for details. If you wish
`to qualify for pediatric exclusivity you should submit a "Proposed Pediatric Study Request". FDA
`generally does not consider studies submitted to an NDA before issuance of a Written Request as
`responsive to the Written Request. Applicants should obtain a Written Request before submitting
`pediatric studies to an NDA.
`
`In addition, submit three copies of the introductory promotional 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
`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, MD 20857
`
`Please submit one market package of the drug product when it is available.
`
`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, call LTJG Raquel Peat, Regulatory Health Project Manager, at (301) 827-
`2125.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Mark J. Goldberger, M.D., M.P.H.
`Director
`Office of Drug Evaluation IV, HFD-104
`Center for Drug Evaluation and Research
`
`Enclosure: package insert, immediate container, and carton label
`
`

`

`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Mark Goldberger
`9/12/03 05:27:16 PM
`
`