15:25
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`• •
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`NO. 100
`
`DIVISION OF ONCOLOGY nRUG PRODUCTS
`Center for Drug EvaluatioD and Research, IIFD-ISO
`Parklawn Building
`5600 Fishers Lane, RoclM1le, MD 20857
`
`To:
`
`John WOl2allaf LILLY
`
`From: Alvis Dunson, Project Manager
`
`Fax:
`
`317276-1652
`
`Phone: 317276-5052
`
`Pax:
`
`301-594-0498
`
`P'-- 301-594-5767
`
`Pagea: 2 Oncluding this page)
`
`Date: December 21,1999
`
`Re:
`
`INO 40.0G1/serial nos. 191and 195
`o Urgent ~or Review
`
`0 Pie ••• Comment 0 Pleue Reply
`
`o Please Recycle
`
`TInS DOCUMENT [S INTENDED ONLY FOR TIlE us.e. OF 11-JE PARTY TO WHOM IT IS ADDRESSED AND MAY
`CONTAIN INFORMATJON mAT 1S PRIVILEGED, CONFIDENTIAL AND PROTECTED FROM DISCLOSURE UNDER
`APPUCABLE LAW. )f you are not the addressee, or a person autl10rized to del iver the document to the addressee, you are hereby
`notified that any review, disclosure, dissemination or other action based on the content of the communication is not authorized. If
`you have received this document in error, please immediately 1lotify uS by telephone and return it to llS at the above address by mail.
`Thank you .
`
`• Co",ments&
`
`Please refer to your submissions dated November 8 and December 3, 1999, for LY231S14 {MTA}.
`
`We have reviewed this submission and have the following comments.
`
`At this point in the review, the Medical Officer does not support adding vitamins to your ongoing
`pivotal, randomized trial in mesothelioma. Thus, the pivotal trial in malignant mesothelioma (H3E(cid:173)
`MC-JMCH) should not be altered at this stage. A few reasons follow.
`
`First, no statistical plan has been submitted to guide how the data is to be evaluated andJor compared
`to the prior accumulated data. Second, at the June 25, 1999, you committed to completing the 280
`patient trial even if the results are positive at the interim analysis; adding vitamins to the trial at this
`time appears to be a deviation from that commitment. Third. the infonnation provided in the Annual
`Report (serial #191) about the toxicities in the trial (pages 45-46) does not appear to support the
`addition of vitamins. You may want to design a randomized trial of MTA +/- vitamins in
`mesothelioma. lfyou believe that vitamin administration will be an important aspect of the MTA
`
`DEC 21 1999 15:08
`
`301 594 0498
`
`PAGE. 01
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`CONFIDENTIAL
`ELAP00013308
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`TX 1463
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`Lilly Ex. 2104
`Sandoz v. Lilly IPR2016-00318
`
`

`
`12/21/99 .
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`15:25
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`N
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`NU.1UU
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`“U4
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`IND 40,051
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`2
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`December 21 , 1999
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`i
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`label, this may be an important trial that can provide convincing evidence with regard to efficacy and
`safety of MTA with and without vitamins.
`Ifyou have any questions please call me at (301) 594-5767.
`
`Thank yo
`
`nflwq
`
`vis unson
`
`DEC 21 1999 15328
`
`321 S94 6498
`
`PFIGE.B2
`
`CONFIDENTIAL
`ELAP00013309
`
`Lilly Ex. 2104
`Sandoz V. Lilly IPR20l6-00318
`
`Lilly Ex. 2104
`Sandoz v. Lilly IPR2016-00318