",~'"g"KV'C£S."~,
`
`( E DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`""~4,-:
`~." t-
`
`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
`
`NDA 21-677
`NDA 21-462/S-001
`
`Eli Lily and Company
`Attention: John Worzalla
`Research Scientist, U.S. Regulatory Affairs
`Lilly Corporate Center
`Indianapolis, IN 46285
`
`Dear Mr. Worzalla:
`
`
`Please refer to your new drug application (NDA) dated November 3, 2003, received November 4,
`2004, submitted under section 505(b) ofthe Federal Food, Drug, and Cosmetic Act for AlimtaCI
`(pemetrexed for injection).
`
`We acknowledge receipt of
`
`
`your submissions dated December 4, 10 and 23, 2003; March 3, i 5, 30,
`and 31; April 14 and 23; May 13 and 20; June 22, 29, and 30; July 12 and 13; and August 3,5,13, and
`16,2004. Finally, we acknowledge your August 12,2004 supplement to NDA 21-462, which provides
`for updating the labeling in the "parent NDA."
`
`This new drug application provides for the use of AlimtaCI (pemetrexed for injection) as a single-agent
`for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after prior
`chemotherapy.
`
`We completed our review of
`
`
`the application and relevant supplement are approved effective on the date of
`
`this application, 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 and required patient labeling. Accordingly,
`this letter. Marketing of
`the referenced
`
`this drug product and related activities must adhere to the substance and procedures of
`
`accelerated approval regulations.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert
`and patient package insert). 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
`ofthe FPL as soon as it is available but no more than 30 days after it is printed. Individually mount 15
`ofthe copies on heavy-weight paper or similar materiaL. For administrative purposes, designate this
`submission "FPL for approved NDA 21-677 and supplement NDA 21-462/8-001." Approvalofthis
`submission by FDA is not required before rhe labeling is used. .
`
`

`

`NDA 21-677/NDA 21-462/S-001
`Page 2
`
`
`adequate and well-controlled studies to verify and describe clinical benefit. We remind you of
`
`
`Products approved under the accelerated approval regulations, 21 CFR 314.510, require further
`your
`
`post marketing study commitments specified in your submission dated August 3, 2004. These
`
`commitments, along with any completion dates agreed upon, are listed below.
`
`
`1. H3E-MC-JMDB: Multicenter, Randomized Phase II Trial of AUMT A lI and Cisplatin
`Versus GEMZARII and Cisplatin in Patients with Locally Advanced or Metastatic Non-
`Small Cell Lung Cancer
`
`Status: Recently began enrollng. There are approximately 3/1700 patients enrolled.
`Last patient visit: June 2008
`
`Final study report: November 2008
`
`
`2. H3E-MC-JMEN: Multicenter, Randomized Phase II Study of
`
`
`Maintenance Therapy with
`Single-Agent Alimta versus Best Supportive Care after Treatment with Gemcitabine plus
`Carboplatin in Chemonaive Patients with Advanced Non-Small Cell Lung Cancer
`Status: Protocol is presently under special protocol assessment at DODP with Protocol
`approval planned for December 2004.
`
`Planned number of
`
`
`patients enrolled: 660
`
`First patient visit: March 2005
`
`Last patient visit: May 2008
`
`Pinal study report: November 2008
`
`
`Submit final study reports to NDA 21-462 as a supplemental application. For administrative purposes,
`be clearly designated
`
`all submissions relating to these postmarketing study commitments must
`
`
`"Subpart H Postmarketing Study Commitments."
`
`administration, and new dosing regimens are required to contain an assessment of
`
`
`All applications for new active ingredients, new dosage forms, new indications, new routes of
`the safety and
`the product in pediatric patients unless this requirement is waived or deferred. We are
`waiving the pediatric study requirement for this application.
`
`effectiveness of
`
`
`In addition, we note your following postmarketing study commitments, specified in your submission
`the accelerated approvaL. This commitment is listed
`
`dated August 3,2004, that are not a condition of
`
`
`below.
`
`H3E-MC-JMGX: Multicenter, Randomized Phase II Trial of Alimta 500 mg/m2 versus 900
`mg/m2 in Patients with Locally Advanced or Metastatic (Stage II or Stage IV) Non-Small Cell
`Lung Cancer Who Have Been Previously Treated With Chemotherapy
`
`Status: Actively enrolling with approximately 22/1 000 patients enrolled globally.
`Last patient visit: December 2006
`Final study report: May 2007
`
`

`

`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
`
`8/19/04 11:15:40 AM
`
`
`