Trade Name:
`
`Generic Name:
`
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`APPLICATION NUMBER:
`
`205776Orig1s000
`
` Rasuvo 7.5 mg/0.15 mL, 10 mg/0.20 mL, 12.5 mg/0.25
`mL, 15 mg/0.30 mL, 17.5 mg/0.35 mL, 20 mg/0.40 mL,
`22.5 mg/0.45mL, 25 mg/0.50 mL, 27.5 mg/0.55 mL, and
`30 mg/0.60 mL.
`
`methotrexate injection
`
`Medac Pharma, Inc.
`
`July 10, 2014
`
`For the management of patients with severe, active
`rheumatoid arthritis (RA) and polyarticular juvenile
`idiopathic arthritis (pJIA), and for symptomatic control
`of severe, recalcitrant, disabling psoriasis in adults who
`are not adequately responsive to other forms of therapy.
`
`
`
`Sponsor:
`
`
`Approval Date:
`
`
`Indication:
`
`
`Medac Exhibit 2069
`Frontier Therapeutics v. Medac
`IPR2016-00649
`Page 00001
`
`

`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`205776Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology / Virology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`X
`
`X
`
`X
`X
`
`X
`X
`X
`
`X
`X
`X
`X
`X
`
`X
`X
`
`Page 00002
`
`

`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`205776Orig1s000
`APPROVAL LETTER
`
`
`
`
`
`
`
`Page 00003
`
`

`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 205776
`
`
`Medac Pharma, Inc.
`c/o B&H Consulting Services, Inc.
`50 Division Street, Suite 206
`Somerville, NJ 08876
`
`Attention: Stephanie Pierson, RAC
`
` Vice President
`
`Dear Ms. Pierson:
`
`Please refer to your New Drug Application (NDA) dated September 10, 2013, received
`September 10, 2013, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Rasuvo (methotrexate injection) 7.5 mg/0.15 mL, 10 mg/0.20 mL,
`12.5 mg/0.25 mL, 15 mg/0.30 mL, 17.5 mg/0.35 mL, 20 mg/0.40 mL, 22.5 mg/0.45mL,
`25 mg/0.50 mL, 27.5 mg/0.55 mL, and 30 mg/0.60 mL.
`
`We acknowledge receipt of your amendments dated December 20, 2013, and January 10, 15, 16,
`and 23, February 25 and 28, March 21, April 3, 4, 8, 17, and 30, May 6, 9, 16, 23, 28, and 29,
`and June 4, 12, 17, and July 3, 2014.
`
`This new drug application provides for the use of Rasuvo (methotrexate injection) for the
`management of patients with severe, active rheumatoid arthritis (RA) and polyarticular juvenile
`idiopathic arthritis (pJIA), and for symptomatic control of severe, recalcitrant, disabling psoriasis
`in adults who are not adequately responsive to other forms of therapy.
`
`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 enclosed agreed-upon labeling text.
`
`EXPIRATION DATING PERIOD
`
` A
`
` 17-month expiry dating period is granted for Rasuvo (methotrexate injection) when stored at
`controlled room temperature between 20°C and 25°C (68°F and 77°F) with excursions permitted
`from 15°C and 30°C (59°F and 86°F).
`
`
`
`Reference ID: 3540287
`
`Page 00004
`
`

`
`NDA 205776
`Page 2
`
`
`
`WAIVER OF HIGHLIGHTS SECTION
`
`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert, text for the
`patient package insert, text for instructions for use). Information on submitting SPL files using
`eLIST may be found in the guidance for industry SPL Standard for Content of Labeling
`Technical Qs and As, available at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE CONTAINER LABELS
`
`Submit final printed carton and immediate container labels that are identical to the enclosed
`carton and immediate container labels, as soon as they are available, but no more than 30 days
`after they are printed. Please submit these labels electronically according to the guidance for
`industry Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical
`Product Applications and Related Submissions Using the eCTD Specifications (June 2008).
`Alternatively, you may submit 12 paper copies, with 6 of the copies individually mounted on
`heavy-weight paper or similar material. For administrative purposes, designate this submission
`“Final Printed Carton and Container Labels for approved NDA 205776.” Approval of this
`submission by FDA is not required before the labeling is used.
`
`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`We are waiving the pediatric study requirement for ages 0 through 2 years for pJIA because the
`disease is extremely rare in this age group and studies would be impossible or highly impractical.
`
`Reference ID: 3540287
`
`Page 00005
`
`

`
`NDA 205776
`Page 3
`
`
`
`This product is appropriately labeled for use in pJIA patients ages 2 to 17 years. Therefore, no
`additional studies are needed in this pediatric group.
`
`We are waiving the pediatric study requirement for the psoriasis indication because there is
`evidence strongly suggesting that the benefit for this drug product does not outweigh the risk in
`all pediatric age groups.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. Form FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`
`
`Reference ID: 3540287
`
`Page 00006
`
`

`
`NDA 205776
`Page 4
`
`
`
`If you have any questions, call Sadaf Nabavian, Senior Regulatory Project Manager, at (301)
`796-2777.
`
`
`
`
`
`
`
`
`
`Reference ID: 3540287
`
`Enclosures:
`Content of Labeling
`Carton and Container Labeling
`
`Sincerely,
`
`{See appended electronic signature page}
`
`
`
`
`
`Tatiana Oussova, M.D., M.P.H.
`
`
`Deputy Director for Safety
`
`Division of Dermatology and Dental Products
`Office of Drug Evaluation III
`
`
`Center for Drug Evaluation and Research
`
`
`
`
`
`
`
`
`
`
`
`
`
`{See appended electronic signature page}
`
`Badrul A. Chowdhury, M.D., Ph.D.
`Director
`
`
`
`
`Division of Pulmonary, Allergy, and
`Rheumatology Products
`
`
`Office of Drug Evaluation II
`
`Center of Drug Evaluation and Research
`
`Page 00007
`
`

`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`TATIANA OUSSOVA
`07/10/2014
`
`SARAH K YIM
`07/10/2014
`Signing for Badrul Chowdhury, M.D., Ph.D.
`
`Reference ID: 3540287
`
`Page 00008