It\snrurs
@ THnScnppsRssEARCH
10666 North Toney PinesRoad
LaJolk, CA 92037
Tebphone619.455.9100
EMBARGOEI)
by the American Academyof Neurology
until Thursday,May 5, L994,12:00noonEDT
X'or information:
Robin B. Goldsmith
(619)554-8134
# 050594
MEDIA ADVISORY: Drs. Beutler,Sipeand Rominewill be availablefor a pressbriefing
on Thursday,May 5, t994, 10:30a.m. in the News Room of the AmericanAcademyof
Neurology, Lanai Suite#148, SheratonWashingtonHotel, Washington,D.C. Press
briefing room tel. no.: (202) 328-5636.
CLADRIBINE FAVORABLY ALTERS TIIE CLINICAL COTJRSEOF'
PROGRESSIVE MI.JLTIPLE SCLEROSIS
Washington,D.C. May 5, 1994- A powerful anti-lymphocytedrug developedand tested
at The ScrippsResearchInstitutein La Jolla, Calif., hasbeendemonstrated
to favorably
influencethe courseof chronicprogressivemultiple sclerosis(MS) and showspromiseas a
therapy for the disorder.
(2-CdA), in the treaffnentof multiple
The use of Cladribine,or 2-chlorodeoxyadenosine
sclerosiswas consideredby the researchersafter extensiveexperiencewith the drug in the
successfultreatmentof lymphoid leukemias,particularlyhairy cell leukemia.In a large
study conductedat Scrippsin 1990, 146hairy cell leukemiapatientswere given a single
doseof z-CdA and 86% achieveda completeremission.
Multiple sclerosisaffectsapproximately300,000peoplein the United States.Of these,
aboutone-halfto one-thirdsuffer from chronicprogressivemultiple sclerosis,a severely
disablingdiseaseof the centralnervoussystemwhich involvesthe destructionof the
insulatingsheath,or myelin, that coversthe nervefibers. Musclecoordination,visual
sensationand other signalsare slowedor blocked.Patientswith the diseasesuffer from
MORB
Page2 -
cladribine FavorablyAlters clinical courseof progressive
Multiple Sclerosis
fatigue, difficulty walking, spasticity,muscleweakness,tremor, and impairedthinking and
reasoning.Somepatientsdevelopcompleteparalysis.
While no one is certainof the causeof MS, many scientistsbelievethat autoimmune
mechanismsplay a role, theorizingthat the white blood cells of the immunesystemattack
the myelin sheaththat insulatesthe nerves.Cladribine was testedin this study to determine
whetherselectivelymphocytedepletioncould slow or halt clinical diseaseprogressionand
allow patientsto improve.
Jack C. Sipe, M.D., Head of the Division of Neurologyat ScrippsClinic, presentedthe
results of the clinical trial today at the annualmeetingof the American Academy of
Neurology in Washington,D.C. The title of the presentationwas, "CladribineFavorably
Alters the Clinical Courseof ProgressiveMultiple Sclerosis." The resultsalsohavebeen
submittedto a major medicaljournal for publication.
Accordingto Dr. Sipe, "Immunosuppressive.therapy
haspreviouslybeenusedin patients
with multiple sclerosis,but noneof the prior treatmentsapproachin efficacythe results
that we have seenwith Cladribine.It hasshowna stabilizingeffect on the neurologicstatus
of the MS patientswho were studied. We are looking forward to obtaining results from a
multi-centertrial which is in the planningstages.
"
ErnestBeutler, M.D., Chairmanof the Departmentof Molecularand Experimental
Medicine and co-developerof 2-CdA, organizedand led the multidisciplinaryteamthat
performedthesestudies.He explains,"Thereis no questionthat Cladribinefavorably
influencesthe clinical courseof chronicprogressivemultiple sclerosis.It is an
immunosuppressivedrug with potential side effects and long-term toxicity that may as yet
MORE
Page3 -
cladribine Favorably Alters clinical course of progressive
Multiple Sclerosis
be unknown. Therefore,the advisabilityof using this drug in the treatmentof MS needsto
be establishedin large clinical trials which are now being planned."
This major studywas performedwith grantsof more than $3 million from the General
Clinical ResearchCenterof the NationalInstitutesof Health (NIH), the Neurologic
DiseaseInstinrrcof the NIH, the OrphanDrug Branchof the Food and Drug
Administration,and the Samand RoseSteinCharitableTrust Fund.
In 1990, Drs. Beutlerand Sipetreatedfour patientswith six monthly dosesof 2-CdA, with
clear evidenceof improvementboth clinically and as evidencedby increasedperformance
on a generallyacceptedneurologicrating scale.Encouragedby theseresults,they designed
the current studywith the collaborationof JamesA. Koziol, Ph.D., biostatisticianin the
Departmentof Molecularand ExperimentalMedicine;JohnS. Romine,M.D., Division of
Neurology; RobertMcMillan, M.D., Division of Hematologyand Oncology;and Jack
Zyroff, M.D., Division of Neuroradiology.
Forty-eightchronicprogressiveMS patientsparticipatedin a double-blinded,placebocontrolledstudyof the effectiveness
of z-CdA administeredby centralvenouscatheter.
Patientswere pairedby age, sex, durationand severityof the disease.Twenty-fourpatients
were randomizedto four monthly infusionsof 2-CdA while the other 24 were given saline
infusions.Becauseof the positiveresultsat one year, the formal studywas terminatedand
the placebogroup was treatedwith one-halfthe doseof z-CdA given to patientsduring the
first year of the study.
At monthly examinations,the patients'levelsof neurologicdisability were measuredby
standardrating scales.In addition,the spinalfluid was testedto measureimmuneactivity
MORE
Page4 -
cladribine Favorably Alters clinical course of progressive
Multiple Sclerosis
and the volume of brain lesionswas determinedby magneticresonanceimaginginitially
and at six, twelve, eighteenand twenty-fourmonths.
Cladribineadministrationwas associated
with a highly significantdifferencein neurologic
rating scores.The neurologicstatusof patientsgiven Cladribinewas slightly improvedor
stabilized;patientsgiven the placebocontinuedto manifesta declineof neurologicstatus.
Further, the total volumeof MS brain lesionsdecreased
in patientstreatedwith Cladribine.
In addition, therewas a significantdifferencein the spinalfluid findings of patients
receivingCladribineand thosereceivingthe placebo,suggestingdecreased
autoimmune
activity in responseto Cladribine.
Generally,the drug was well tolerated,but a few problemswere encounteredin the study,
including low plateletcountsin four patients.Also, one patientdevelopedbonemarrow
suppressionfrom which shecompletelyrecoveredwithin six months.One patientdied
from acutelyacquiredhepatitisB, an eventnot consideredby the scientiststo be relatedto
z-CdA.
A multi-centertrial soonwill be implementedunderthe leadershipof the Scrippsgroup.
This trial will makethe experimentaltreatrnentavailableto eligible patientsin various
parts of the country. Patientsare being screenedfor the studyand may call 1-800SCRIPPSfor more information.
###
Ernest Beutler, M.D., may be reachedat the Omni ShorehamHotel, room 315,
telz Q02) 234-0700,Tuesday,May 3, in the afternoon; Wednesday,is,[ay4;
and Thursday, May 5n in the morning.