CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
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`
`
`APPLICATION NUMBER:
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`209472Orig1s000
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`
`OTHER ACTION LETTERS
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`
`
`
`
`
`
`

`

`NDA 209472
`
`
`
`
`
`
` TENTATIVE APPROVAL
`
`
`
`Eagle Pharmaceuticals, Inc.
`
`Attention: Janis A. Picurro
`
`Senior Vice President, Regulatory Affairs
`
`50 Tice Boulevard
`
`Suite 315
`
`Woodcliff Lake, NJ 07677
`
`
`
`Dear Ms. Picurro:
`
`
`
`Please refer to your new drug application (NDA) submitted and received on
`
`December 30, 2016, and your amendments, submitted pursuant to section 505(b)(2) of
`
`the Federal Food, Drug, and Cosmetic Act for Pemfexy (pemetrexed injection)
`
`
`25 mg/mL.
`
`
`We acknowledge receipt of your amendment dated August 9, 2019, which constituted a
`
`complete response to our October 26, 2017, action letter.
`
`
`This NDA provides for the use of Pemfexy:
`
`
`•
`
`
`
`in combination with cisplatin for the initial treatment of patients with locally
`advanced or metastatic, non-squamous, non-small cell lung cancer (NSCLC);
`
`as a single agent for the maintenance treatment of patients with locally advanced
`or metastatic non-squamous NSCLC whose disease has not progressed after
`four cycles of platinum-based first-line chemotherapy;
`
`
`as a single agent for the treatment of patients with recurrent, metastatic
`non-squamous NSCLC after prior chemotherapy; and
`
`•
`
`
`•
`
`
`•
`
`Reference ID: 4504211
`
`in combination with cisplatin for the initial treatment of patients with malignant
`
`pleural mesothelioma whose disease is unresectable or who are otherwise not
`candidates for curative surgery
`
`
`We have completed our review of this application, as amended. It is tentatively
`approved under 21 CFR 314.105 for use as recommended in the agreed-upon enclosed
`labeling (text for the Prescribing Information, Patient Package Insert, and Carton and
`Container labeling). This determination is based upon information available to the
`Agency at this time, [i.e., information in your application and the status of current good
`manufacturing practices (cGMPs) of the facilities used in the manufacture and testing of
`
`

`

`NDA 209472
`Page 2
`
`
`the drug product]. This determination is subject to change on the basis of any new
`information that may come to our attention.
`
`Final approval of your application is subject to expiration of a period of patent protection
`and/or exclusivity. Therefore, final approval of your application under section 505(c)(3)
`of the Act [21 U.S.C. 355(c)(3)] may not be granted before the period has expired.
`
`A listed drug(s) upon which your application relies is subject to a period of patent
`protection and your application contains a certification(s) to one or more patents under
`section 505(b)(2)(A)(iv) of the FD&C Act stating that the patent(s) is/are invalid,
`unenforceable, or will not be infringed by your manufacture, use, or sale of, this drug
`product under this application (“paragraph IV certification”).
`
`Section 505(c)(3)(C) of the FD&C Act provides that approval of a new drug application
`submitted pursuant to section 505(b)(2) of the FD&C Act that includes a paragraph IV
`certification shall be made effective immediately, unless an action is brought for
`infringement of one or more of the patents that were the subject of a paragraph IV
`certification. If such a patent infringement action is brought prior to the expiration of
`45 days from the later of the date the notice provided under section 505(b)(3) is
`received by the patent owner or approved application holder, your application is subject
`to a 30-month stay of approval, unless other conditions are met. You notified us that you
`complied with the requirements of section 505(b)(3) of the FD&C Act.
`
`In addition, you have notified the Agency that the patent owner and/or approved
`application holder has initiated a patent infringement suit against you with respect to
`patent 7,772,209 in the District Court of Delaware (Civil Action No. 17-cv-1293).
`
`Therefore, final approval cannot be granted until:
`
`
`(1)
`
`(2)
`
`a. expiration of the 30-month period provided for in section 505(c)(3)(C)
`beginning on the later of the date of receipt by any owner of the listed
`patent or application holder of the notice required under section 505(b)(3),
`unless the court has extended or reduced the period because of the failure
`of either party to reasonably cooperate in expediting the action, or
`
`b. the date the court decides that the patent(s) is/are invalid or not infringed
`as described in section 505(c)(3)(C)(i), (ii), (iii,) or (iv) of the FD&C Act, or,
`
`c. the listed patent(s) has/have expired, and
`
`we are assured there is no new information that would affect whether final
`approval should be granted.
`
`
`To obtain final approval of this application, submit an amendment two or six months
`prior to the: (1) expiration of the patent or (2) date you believe that your NDA will be
`eligible for final approval, as appropriate. In your cover letter, clearly identify your
`
` amendment as “REQUEST FOR FINAL APPROVAL”. This amendment should provide
`the legal/regulatory basis for your request for final approval and should include a copy
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4504211
`
`

`

`NDA 209472
`Page 3
`
`
`of any relevant court order or judgment settlement, or licensing agreement, as
`appropriate. In addition to a safety update, the amendment should also identify
`changes, if any, in the conditions under which your product was tentatively approved,
`i.e., updated labeling; chemistry, manufacturing, and controls data; and risk evaluation
`and mitigation strategy (REMS). If there are no changes, clearly state so in your cover
`letter. Any changes require our review before final approval and the goal date for our
`review will be set accordingly.
`
`Until we issue a final approval letter, this NDA is not approved.
`
`Please note that this drug product may not be marketed in the United States without
`final agency approval under section 505 of the FD&C Act. The introduction or delivery
`for introduction into interstate commerce of this drug product before the final approval
`date is prohibited under section 501 of the FD&C Act and 21 U.S.C. 331(d)..
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`new active ingredients (which includes new salts and new fixed combinations), 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 in pediatric patients unless this requirement is waived, deferred,
`or inapplicable.
`
`We note that if this application is ultimately approved, you will need to meet these
`requirements.
`
`METHODS VALIDATION
`
`
`We have not completed validation of the regulatory methods. However, we expect your
`continued cooperation to resolve any problems that may be identified.
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4504211
`
`

`

`NDA 209472
`Page 4
`
`
` If you have any questions, call Autumn Zack-Taylor, M.S., Regulatory Health Project
`
`
`
`Manager, at (240) 402‐5913, or in her absence, Meredith Libeg, Senior Regulatory
`
`Health Project Manager, at (301) 796-1721.
`
`
`
`Sincerely,
`
` {See appended electronic signature page}
`
`
`
`Jeffery Summers, M.D.
`Deputy Director of Safety
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`
`
`
`
`
`
`ENCLOSURE(S):
` Content of Labeling
`
`o Prescribing Information
`
`o Patient Package Insert
`
`
` Carton and Container Labeling
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4504211
`
`34 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`JEFFERY L SUMMERS
`10/09/2019 05:11:18 PM
`
`Reference ID: 4504211
`
`

`

`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`
`
`
`Food and Drug Administration
`
`Silver Spring MD 20993
`
`
`
`
`
`
`NDA 209472
`
`TENTATIVE APPROVAL
`
`
`Eagle Pharmaceuticals, Inc.
`
`Attention: Adrian Hepner, M.D., Ph.D.
`Chief Medical Officer
`50 Tice Boulevard, Suite 315
`Woodcliff Lake, NJ 07677
`
`
`Dear Dr. Hepner:
`
`
`Please refer to your New Drug Application (NDA) submitted and received December 30, 2016,
`and your amendments, submitted under section 505(b)/pursuant to section 505(b)(2) of the
`Federal Food, Drug, and Cosmetic Act for Pemfexy (pemetrexed injection) 25 mg/mL.
`
`This NDA provides for the use of Pemfexy (pemetrexed injection) 25 mg/mL for the treatment
`of patients with
`
`
`
`
`locally advanced or metastatic nonsquamous non-small cell lung cancer in combination
`with cisplatin;
`locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease
`has not progressed after four cycles of platinum-based first-line chemotherapy, as
`maintenance treatment;
` metastatic nonsquamous non-small cell lung cancer after prior
`
` chemotherapy as a single agent; and
`malignant pleural mesothelioma whose disease is unresectable or who are otherwise not
`
` candidates for curative surgery in combination with cisplatin.
`
`
`
`
`
`
`
`
`
`
`
`
`We have completed our review of this application, as amended. It is tentatively approved under
`21 CFR 314.105 for use as recommended in the agreed-upon enclosed labeling (text for the
`package insert, patient package insert, and carton and immediate container labels). This
`determination is based upon information available to the Agency at this time, [i.e., information in
`your application and the status of current good manufacturing practices (cGMPs) of the facilities
`used in the manufacture and testing of the drug product]. This determination is subject to change
`on the basis of any new information that may come to our attention.
`
`The listed drug upon which your application relies is subject to a period of patent protection and
`therefore final approval of your application under section 505(c)(3) of the Act [21 U.S.C.
`355(c)(3)] may not be made effective until the period has expired.
`
`
`Reference ID: 4172768
`
`(b) (4)
`
`

`

`NDA 209472
`Page 2
`
`
`Your application contains certifications to each of the patents under section 505(b)(2)(A)(iv) of
`the Act stating that the patents are invalid, unenforceable, or will not be infringed by your
`manufacture, use, or sale of, this drug product under this application (“Paragraph IV
`certifications”).
`
`
`Section 505(c)(3)(C) of the Act provides that approval of a new drug application submitted
`pursuant to section 505(b)(2) of the Act shall be made effective immediately, unless an action is
`brought for infringement of one or more of the patents that were the subject of the paragraph IV
`certifications. This action must be taken prior to the expiration of forty-five days from the date
`the notice provided under section 505(b)(3) is received by the patent owner/approved application
`holder. You notified us that you complied with the requirements of section 505(b)(3) of the Act.
`
`In addition, you have notified the Agency that the patent owner and/or approved application
`holder has initiated a patent infringement suit against you with respect to patent 7,772,209 in the
`District Court of Delaware (Civil Action No. 17-cv-1293). Therefore, final approval cannot be
`granted until:
`1. a. expiration of the 30-month period provided for in Section 505(c)(3)(C) beginning
`
`on the date of receipt of the 45-day notice required under Section 505(b)(3),
`unless the court has extended or reduced the period because of the failure of either
`party to reasonably cooperate in expediting the action, or
`b. the date the court decides that the patent is invalid or not infringed as described in
`section 505(c)(3)(C)(i), (ii), (iii,) or (iv) of the Act, or,
`c. the listed patent has expired, and
`we are assured there is no new information that would affect whether final
`approval should be granted.
`
`
`To obtain final approval of this application, submit an amendment two or six months prior to the:
`1.) expiration of the patent or 2.) date you believe that your NDA will be eligible for final
`approval, as appropriate. In your cover letter, clearly identify your amendment as “REQUEST
`FOR FINAL APPROVAL”. This amendment should provide the legal/regulatory basis for
`your request for final approval and should include a copy of any relevant court order or judgment
`settlement, or licensing agreement, as appropriate. In addition to a safety update, the amendment
`should also identify changes, if any, in the conditions under which your product was tentatively
`approved, i.e., updated labeling; chemistry, manufacturing, and controls data; and risk evaluation
`and mitigation strategy (REMS). Before submitting your amendment, we also recommend you
`review the updated prescribing information for another approved product as an example [e.g.,
`Alimta (pemetrexed for injection) for intravenous use]. If there are no changes in your
`amendment, clearly state so in your cover letter. Any changes require our review before final
`approval and the goal date for our review will be set accordingly.
`
`Until we issue a final approval letter, this NDA is not deemed approved.
`
`
`
`2.
`
`
`
`
`
`Reference ID: 4172768
`
`

`

`NDA 209472
`Page 3
`
`
`Please note that this drug product may not be marketed in the United States without final agency
`approval under Section 505 of the Act. The introduction or delivery for introduction into
`interstate commerce of this drug product before the final approval date is prohibited under
`Section 501 of the Act and 21 U.S.C. 331(d).
`
`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 in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`We note that if this application is ultimately approved, you will need to meet these requirements.
`
`METHODS VALIDATION
`
`We have not completed validation of the regulatory methods. However, we expect your
`continued cooperation to resolve any problems that may be identified.
`
`If you have any questions, call Autumn Zack-Taylor, M.S., Regulatory Health Project Manager,
`at (240) 402‑5913.
`
`
`
`ENCLOSURE(S):
`Content of Labeling
`Carton and Container Labeling
`
`Reference ID: 4172768
`
`
`
`Sincerely,
`
` {See appended electronic signature page}
`
`Joseph Gootenberg, M.D.
`Deputy Division Director
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`42 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JOSEPH E GOOTENBERG
`10/26/2017
`
`Reference ID: 4172768
`
`