..... :·.Ji
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`·:·
`DECEMBER 1997 • VOL.32 • NO .12· ;
`
`A PEER-REVIEWED JOURNAL FOR MANAGED CARE AND HOSPITAL DECJSJON MAKERS
`
`.. fiN ·PffAliMACY -LI.BRARY
`
`• Perspectives on the
`new JNC VI·guidelines for
`the T:x of hypertension
`N.M. KAPLAN, MD
`
`• Focus on danaparoid:.
`For DVT prophylaxis
`with potential use. in mT
`MJ. CAMPBELL, BSc PHARM, PHARMD
`
`• Developing systematic,
`information-driven
`·
`disease management
`interventions: A model
`D. KilNNERLY, MD, PHD, C. HA:rw!G, MS, RPH, AND
`V.S. CRANI!, MBA, RPH
`.
`
`WASHINGTON UPDATE
`Final reform bill 'modernizes'
`FDA, permits dissemiriation of
`off-label and economic data.
`
`Index to volume 32
`
`Abstracts from current literature
`
`,..
`
`Page 1 of 3
`
` Exh. 1013
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`Mylan Ex. 1013
`IPR Petition - USP 6,335,031
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`1
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`j
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`f.l
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`1
`·.
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`FOCUS
`~
`Danapaioid: A heparlnoid for ovr
`1211
`prophylaxis with potential fot' USe tn m.'I'
`.
`.
`.MAlliA J. Ci..MPBI!LL, BS PH:ARM, PHARMD
`Danaparoid (Orgara:n), approved ln the
`Up.ited Sta.t.es for the prophyla:.ds. of deep
`venous thrombosis ln patients undergoing
`elective hip replacement .surgery, is under
`btudy or already approved in other countties
`fol' use in heparin-induced thrombocytopenia.
`This-Focus article considers danaparoid's use
`and formulary role in the United States for
`both .approved and unapproved indications.
`
`COVER ARTICLE
`
`Perspectives on the n~ JNC VI
`1224-
`~delines for the treatment of hypertension
`NoRMAN M. KA.l'LAN, MD
`The just-published sixth report of the Joint
`National Committee on Prevention, Detection,
`Evaluation, and 'freatment of High Blood
`Pressure (JNC vp is expected to be a widely
`used guidance for hypertension management.
`Dr. Kaplan-who served as chair of the
`section on treatment for JNC VI---reviews the
`report's drug therapy recommendations,
`noting changes from the JNC V report. The
`report's new rlsk-st:ratifica.tion guidance,
`·considerations for individualizing drug therapy,
`and advice on use of long-acting fonnulations
`.and combination therapy are presented.
`
`ORIGINAL ARTICLE
`
`Devclopingsystematic, ~. 1232
`dJsease management.Jnt.e.rventio:os: A model
`Dow.m Kl!NNmu.Y, MD, PHD, C!nus HA:rwlG, Ms; RPH, AND
`VICKI S, CRANi!, MBA., RPH
`This article presents a conceptual model
`for disease management development,
`hig:hllghting seven general steps !D ensure
`a comprehensive and properly ordered ·
`approach. The model is illustrated in a
`step-by-step case study of a population-based
`asthma management program aeveloped at
`. the authors' hospital system. I!i adc!ition to
`reporting the outcomes they've achieved .and
`ongoing program fn:J.provements, the. authors
`offer their insightS on ways to integrate
`dlsease management and P & T Committee
`functions,
`
`DEPARTMENTS
`
`FDA news and product notes
`• News on eight new molecular entities
`(Anzemet, Avapro, Corlopam, Gabitrll,
`GenESA, Infergen, Requl:p. Seroquel), .
`four new indications, and three drugs
`nearing .approval
`
`1196
`
`Con#nuedonpage1192
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`Printed ln the USA.
`
`FoRMULARY • VoL. S2 • DECEM!la!1997 1191
`
`Page 2 of 3
`
` Exh. 1013
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`

`
`This material may be protected by Copyright law (fitle·17 U.S. Code)
`
`On a scale of 1 Oow) to 10 (high),
`HMOs gave their P1;3Ms an overall
`score of 6.2, down from 6.3 in 1996.
`That follows a drop from 7.2 to 6.3
`the previous year.
`Especially noteworthy ls that just
`50% of HMOs gave their PBM an
`. overall rating of 7 or higher in 1997;
`· whereas 61% did in 1996.
`Moreover, HMOs rated PBMs
`lower on almost all of ti:le 21 specific
`PBM functions evaluated. Many of
`
`the highest~rated functions were o~
`erational or administrative in nature,
`such· as pharmacy network adminis(cid:173)
`tration (rated 8.3) and claims p1'o~
`cessmg (rated 7.1), whereas more
`clinical functions (disease manage(cid:173)
`ment, DUR, formulary management)
`fared less well. The figu;re (see pre(cid:173)
`viouS page) presents average ratings
`for selected PBM functions.
`In a separate survey of 561 HMOs
`conducted in early 1997, PBMI
`
`found that just 45 of them Cm<:>stly
`staff- and group-model plans) do
`not contract with a PBM for any ser(cid:173)
`vice. Of those· that do use PBMs,
`however, .only 1 'JOAl said they use. a
`PBM to manage their formulary.
`The results of the satisfaction .sur(cid:173)
`vey are pub.lished in PBMI's 1997
`Pharmacy Brmefit Manager Cus(cid:173)
`tomer Sat(.sjac#on Survey Report,
`which also includes findings on large
`employers' satisfaction with PBMs.
`
`New acetylcholliiesterase inhibitor shows promise, in largest Alzheimer's trial to ~te
`
`II The investigational brain-selec(cid:173)
`tive · acetylcholinestemse inhibitor
`ENA-713 improves cognition, global
`functioning, and activities of daily liv(cid:173)
`ing in patients with Alzheimer's dis(cid:173)
`ease, according to results iepo:rred at
`the 16th World Congress of Neurol(cid:173)
`ogy, held recendy in Buenos Aires.
`"The development of drugs like
`ENA-713 should help break down
`the nihilism that surrounds the pro(cid:173)
`gressive degenerative process of this
`disease," said Howard Feldman, MD,
`. clinical associate professor of neurol(cid:173)
`ogy, University of Btitisli Columbia,
`Vancouver, Cariada, and an investi~
`gator in trials involving the drug.
`The reported fmdings are based
`on 6-month follow-up in 2,096 pa(cid:173)
`tients with symptomatic mild to mod(cid:173)
`erate Alzheimer's disease who were
`rando:mized to treatment with high-·
`dose (6 to. 12 mg/day) or low-dose
`(1 to 4 mg/day) ENA-713 or placebo.
`The mean .age of study parti~i­
`pants was 73 years, and 94% had
`other illnesses requiring medication.
`All patients were participants in the
`3,300-patient ongoing Alzheimer's
`Disease with ENA-713 (ADENA) pro(cid:173)
`gram, the largest global trial of an
`Alzheimer's ·medication to date, and
`will be followed for up to 2 years. '
`Placebo recipients worsened on,
`the three primary efficacy measures,
`while patients assigned to ENA-713,
`particularly the high-dose group, ei(cid:173)
`ther improved or showed less de(cid:173)
`cline compared with placebo.
`
`1208
`
`FgRMUI.ARY • VOL. 32 • DECEMBER 1997'
`
`Placebo group scores worsened
`by 4.15 points on the cognitive scale
`of the Alzheimer's Disease .Assess(cid:173)
`ment Scale (ADAS-cog). By contrast,:
`ADAS-cog scores improved by 0.79
`points in patients receMng ENA-713.
`"An annual 7- to 8-point deteri~
`ration on the AD AS-cog scale. i&
`characteristic in mUd to moderate
`Alzheimer's disease," .Dr. Feldmari:
`said. "Thus, the nearly 5-point differ..
`ence in scores between the tr:eat(cid:173)
`ment and placebo groups indicates
`a clinically relevant postponement in
`deterioration of roughly 6 months."
`He added that this magnitude of
`effect on ADAS-cog scores is the
`largest that has been reported for an
`acetylcholinesteraSe 'inhibitor.
`Benefit was also observed on the
`Clinician's Interview-Based Impres(cid:173)
`sion of Change (CIBIC) measure,
`which provides a global assessment
`of the patient's condition. Placebo
`group· srores decreased py a mean
`of 0.48 points while scores for the
`high- and low-dos~ ENA~ 713 groups
`decreased by .0.13 and 0.16 points,
`respectively (both significandy lower
`than the decrease with placebo).
`Scores on the third efficacy mea(cid:173)
`sure, the caregiver-rated Progressive
`Deterioration Scale (PDS), were sig(cid:173)
`nificantly better in the high-dose
`ENAw713 group than in the placebo
`group at 6 months. ''This' finding is
`extremely important, because it con(cid:173)
`cerns the aspect of the patients' con(cid:173)
`dition that affects caregivers. most,"
`
`Dr. Feldman said. The PDS evalu(cid:173)
`ates quality-of-life changes.
`"These results mean that about
`30% of patients receiving BNA-713
`treatment will improve in terms of
`cognition, 'global functioning, and
`performance of routine activities, •·
`Dr. Feldman said. The. study also
`feund that benefits were greater in
`pati~ with more ·severe disease.
`The most common side effects
`seen with ENA:-713 in the trial were
`gastrointestinal in nature and were
`generally mild. and transient, rarely
`requiring treatment.
`Dr. Feldman noted that. studie&
`have recendy been launched to ex•
`plore the use of ENA-713 with avail(cid:173)
`able medications. frequendy used to
`treat patients with Alzheimer's dis(cid:173)
`ease, including antipsychotlcs, bM(cid:173)
`zodiazeplnes, and antidepressants ..
`Novartis Pharmaceuticals filed an
`NDA for ENA-713(under the proPfl(cid:173)
`etary name Exelon) in April for tti.e
`treatment of mild to moderate Alz(cid:173)
`heimer's -disease.
`Donepezll HCl ~Arlcept), also a
`second-generation acetylcholin(cid:173)
`esterase inhibitor, \vas recently a~
`proved for this indication. ENA-7:1!3
`is given twice dally, while donepezil
`is taken once a day. To date1. there
`have been no head-t~head compar(cid:173)
`isons of the two drugs; however,
`both have b.een shown to be signifi(cid:173)
`cantly safer and more .effective .. than
`the first-generation iil.cetylcholin(cid:173)
`esterase inhibitor tacrlne HCI. ·i
`
`... ,~ '
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`Page 3 of 3
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` Exh. 1013