http://exhibits.library.stonybrook.edu/mfp/files/original/885a1d25d8fc77628f422b0df0318b61.pdf 88544f1743440479de73cc5abfb1407f PDF Text Text ~»—.a—v 'r-F' . v v.7.” r'»7-WW‘*rn-- .w -H e--mm-mmmwvh—_ n“. 7w..- m..- ___,,._.__._..- -...._._.,._-_._._.,.ww.._r_ . "n.7,, “he, . fl” .v 7V -., a . September . , H Dr. Fred A. Clark, m,,..._.wfl.,q,..s..,w.n ,..__._.,, ,.....y-,- 2i, l97l Jr. A. H. Robins Co. l407 Cummings Drive Richmond, Virginia Dear Fred, as, , have read the andimin (fenfluraminei, I ,vnmnmu’m questions: summary portion of the submission on l6—6l8 (vol. 4.l) with the following NDA .m.‘ is the presentation clear and does .» awn-av air") ‘W‘WJN , "arm-v ~ Wav- 'w "-Y—W-w-va m. ww ~,.. v " Il'm"u1nv\"45’ u rum-- nr-r-—~ claims of the the the 'labelling' section present the data clearly and concisely, sufficient the convince the examiner that the claims for a new drug as 'safe' and 'effectlve' can be substantiated; Are there additbonal studies that should be considered 7 impression is that the summary is written poorly; that redundancy, leaving an impression of 'padding'; and some important issues regarding anorexigenlcs are omitted (persistence of effects, tolerance, dependence, and similarity or dissimilarity to dextroamphetamlne clinically). The summary is complete and sufficient in demonstrating that extensive pharmacologlc, metabolic, toxicologic, and clinical studies were done. Indeed, the amount of data and number of studies are impressive. Yet, i can easily imagine the text Inducing doubts. Some criticisms to be found there is in the My much details are: the same tables inflate/‘9’"?! v: njaqw- whole 1 ,0, it substantiate Does _ 1125's.».- NDA; data is presented in a variety of ways; do not present the salient issues clearly; sections appear as testimonials, diminishing the merit of the data base; and, ,. (a ”W :r. ,rwmfla-a-yv um- words some language is obtuse, leading the examiner to focus rather than ideas. on V �w .. w...” 1.... .. in. Vl‘M' V3:H\*.V( wvmwvu“~' .17.... ... .N..- "mu—v ..—.‘W v»...vnv..v“_..-,W .. .... .... -_,~—-—-.-w—-._.._.m , .. “9......“ .....w v.” -w- ‘wvnwa. .— .- .7 w... -. -2There are two types of data that seem to be treated less adequately than one could wish. One issue in the use of the anorexlgenlcs is the extent to which they inhibit appetite, reduce food intake (or increase metabolism) to yield a gradual loss in weight, and to do so safely. The criticism of dextroamphetamine is the short time it is effective (7tolerance), its abuse potential (?dependence), and the occasional toxicity expressed as insomnia, irritability and tremor. (The same can be said about other stimulating anorexigenics.) i find the comparison of fenfluramine and dextroamphetamine incomplete. The tables on pp. 28—33 are impressive but they lack clinical data. Perhaps the two drugs should be contrasted as to stimulation, secondary effects, abuse potential (has this been demonstrated or tested 7), and dependence. Such a comparison could emphasize the unique properties of fenfluramlne, make the labelling claims distinctive, and allow for approval as separate from the anxiety occasioned by dextroamphetamlne abuse. issue is duration of effect. A principal criticism of dextroamphetamine is a limited period of efficacy. These data doeaot allow for a decision as to whether continued use of fenfluramlne is associated with tolerance, or whether weight loss is sustained. Are increasing doses necessary to sustain weight loss 7 The second v-yw-rw-r ("wuv ‘7...“ n-c clear, With regard to the labelling and useful as far as it goes. cited above, although these answers labelling. section, find It is deficient i may not be it adequate, in the issues necessary for opportunity to discuss the conclusions of the committee meeting on anorexigenlcs with Elmer Garner and Donald F. Klein. Both indicated that the agreement in the committee i FDA had an limited; that no anorexlgenic was really 'proven'; and none sustained wieght loss. l enquired about the questions of tolerance and dependence, and these seemed the principal anxiety in approving new compounds. "Do we really need another drug to be abused ?" l suggested fenfluramine may be significantly different than dextroamphetamine, and Dr. Gardner seemed attentive and interested. He said the FDA was about to allow an NBA for another anorexigenic, and he expressed the opinion that there was little reason to hold up an approval for fenfluramine. was My separately. specific comments are attached. The volume is returned leaving for Europe and will return October 7. l have dictated and typed these notes rather hastily, knowing you wished a reply as eoon as practical. My thanks for the opportunity to read these data, and i trust the submission will not fail. if i can be of help at the FDA, l have no hesitation to meet with them. i am Sincerely yours, Max Fink, M.D. Professor of Psychiatry , 7,. .. , “.7 .7.” we...“ , . � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence to: Clark, F.A. 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