Isis Pharmaceuticals, Inc. Form 10K - page 46

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 KYNAMRO is available only through aRiskEvaluation andMitigationStrategy called theKYNAMROREMS.
In addition, when approved, theFDAor a foreign regulatory authoritymay condition approval on the performance of post-
approval clinical studies or patientmonitoring, which couldbe time consuming and expensive. If the results of suchpost-marketing
studies are not satisfactory, the FDAor a foreign regulatory authoritymaywithdrawmarketing authorizationormay condition
continuedmarketingon commitments fromus or our partners thatmaybe expensive and/or time consuming to fulfill.
Ifwe or others identify side effects after anyof our drugproducts are on themarket, or ifmanufacturingproblems occur
subsequent to regulatory approval, we or our partnersmay lose regulatory approval, orwe or our partnersmayneed to conduct
additional clinical studies and/or change the labelingof our drugproducts includingKYNAMRO, ISIS-APOCIIIRx, ISIS-SMNRx and
ISIS-TTRRx.
We dependon our collaborationwithGenzyme for the development and commercialization ofKYNAMRO.
We have entered into a collaborative arrangementwithGenzyme to develop and commercializeKYNAMRO.
We entered into this collaborationprimarily to:
 fund some of our development activities forKYNAMRO;
 seek andobtain regulatory approvals forKYNAMRO; and
 successfully commercializeKYNAMRO.
Ingeneral, we cannot control the amount and timingof resources thatGenzyme devotes toour collaboration. IfGenzyme
fails to further develop and commercializeKYNAMRO, or ifGenzyme’s efforts are not effective, our businessmaybe negatively
affected.We are relying onGenzyme to obtain additionalmarketing approvals for and successfully commercializeKYNAMRO. Our
collaborationwithGenzymemay not continue or result in the successful commercialization ofKYNAMRO. Genzyme can terminate
our collaboration at any time. IfGenzyme stopped developingor commercializingKYNAMRO, wewouldhave to seek additional
sources for funding andmay have todelayor reduce our development and commercializationprograms forKYNAMRO. IfGenzyme
does not successfully commercializeKYNAMRO, wemay receive limitedor no revenues forKYNAMRO. In addition, Sanofi’s
acquisitionofGenzyme coulddisruptGenzyme or distract it fromperforming its obligations under our collaboration.
IfGenzyme cannotmanufacture finisheddrugproduct forKYNAMRO or the post-launch supply of the activedrug substance
forKYNAMRO,KYNAMROmaynot achieve ormaintain commercial success.
We relyonGenzyme tomanufacture the finisheddrugproduct forKYNAMRO and the long term supplyofKYNAMRO
drug substance. Genzymemaynot be able to reliablymanufactureKYNAMROdrug substance anddrugproduct to support the long
term commercialization ofKYNAMRO. IfGenzyme cannot reliablymanufactureKYNAMROdrug substance anddrugproduct,
KYNAMROmay not achieve ormaintain commercial success, whichwill harmour ability to generate revenue.
Ifwe or ourpartners fail toobtain regulatoryapproval for ourdrugs, includingadditional approvals forKYNAMROor
initial approvals for ISIS-APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx, we or ourpartners cannot sell them in the applicable
markets.
We cannot guarantee that anyof our drugs, including ISIS-APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx, will be safe and
effective, orwill be approved for commercialization. In addition, we cannot guarantee thatKYNAMROwill be approved in
additionalmarkets outside theUnitedStates or for additional indications.We and our partnersmust conduct time-consuming,
extensive and costly clinical studies to show the safety and efficacy of eachof our drugs, includingKYNAMRO, ISIS-
APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx, before a drug canbe approved for sale.Wemust conduct these studies in compliancewith
FDA regulations andwith comparable regulations inother countries.
We andour partnersmaynot obtainnecessary regulatory approvals on a timelybasis, if at all, for anyof our drugs. It is
possible that other regulatory agencieswill not approveKYNAMROor any of our other drugs including, ISIS-APOCIIIRx, ISIS-
SMNRx and ISIS-TTRRx formarketing. If the FDAor another regulatory agencybelieves thatwe or our partners have not sufficiently
demonstrated the safety or efficacy of anyof our drugs, includingKYNAMRO, ISIS-APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx, the
agencywill not approve the specific drugorwill require additional studies, which canbe time consuming and expensive andwhich
will delay or harm commercialization of the drug. For example, inMarch2013 theCHMPof theEuropeanMedicinesAgency
maintained a negative opinion forGenzyme’smarketing authorization application forKYNAMRO as a treatment for patientswith
HoFH.