Isis Pharmaceuticals, Inc. Form 10K - page 45

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If ourdrugdiscovery anddevelopment business fails to compete effectively, ourdrugs, includingKYNAMRO, ISIS-
APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx, will not contribute significant revenues.
Our competitors engage in all areas of drugdiscovery throughout theworld, are numerous, and include, amongothers,major
pharmaceutical companies and specializedbiopharmaceutical firms. Other companies engage indeveloping antisense technology. Our
competitorsmay succeed in developingdrugs that are:
 priced lower thanour drugs;
 safer thanour drugs;
 more effective thanour drugs; or
 more convenient touse thanour drugs.
These competitive developments couldmake our drugs, includingKYNAMRO, ISIS-APOCIIIRx, ISIS-SMNRx and ISIS-
TTRRx, obsolete or non-competitive.
Certain of our partners are pursuingother technologies or developingother drugs either on their ownor in collaborationwith
others, includingour competitors, to treat the same diseases our own collaborative programs target. Competitionmaynegatively
impact a partner’s focus on and commitment to our drugs and, as a result, coulddelayor otherwise negatively affect the
commercializationof our drugs, includingKYNAMRO, ISIS-APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx.
Manyof our competitors have substantially greater financial, technical andhuman resources thanwe do. In addition,manyof
these competitors have significantly greater experience thanwe do in conductingpreclinical testing andhuman clinical studies of new
pharmaceutical products and inobtainingFDA and other regulatory approvals of products for use inhealth care. Accordingly, our
competitorsmay succeed in obtaining regulatory approval for products earlier thanwe do. Marketing and sales capability is another
factor relevant to the competitive positionof our drugs, andwewill relyonour partners toprovide this capability.
RegardingKYNAMRO, some competitors are pursuing a development or commercialization strategy that competeswith our
strategy forKYNAMRO. Other companies are currentlydevelopingproducts that could competewithKYNAMRO. Products such as
microsomal triglyceride transfer protein inhibitors, orMTP inhibitors, andother lipid loweringdrugs other companies are developing
or commercializing couldpotentially competewithKYNAMRO. For example, AegerionPharmaceuticals, Inc. received approval
from the FDA and theEuropeanMedicinesAgency tomarket itsMTP inhibitor, lomitapide, as an adjunct to a low-fat diet andother
lipid-lowering treatments inpatientswithHoFH. Our revenues and financial positionwill suffer ifKYNAMRO cannot compete
effectively in themarketplace.
There are several pharmaceutical andbiotechnology companies engaged in the development or commercialization of
products against targets that are also targets of products inour development pipeline. For example, drugs like tafamadis, diflunisal,
andpatisiran could competewith ISIS-TTRRx, drugs like pradigastat andCAT-2003 could competewith ISIS-APOCIIIRx, and the
earlydevelopment programs designed to treat patientswithSMA could competewith ISIS-SMNRx.
KYNAMRO is, and, followingapproval anyof our other drugs, including ISIS-APOCIIIRx, ISIS-SMNRx and ISIS-TTRRx,
couldbe, subject to regulatory limitations.
TheFDA and foreign regulatory authorities have the authority to impose significant restrictions on an approveddrugproduct
through the product label and on advertising, promotional anddistribution activities. For example:
 KYNAMRO is approved in theUnitedStates as an adjunct to lipid-loweringmedications and diet to reduce low
density lipoprotein-cholesterol, apolipoproteinB, total cholesterol, andnon-highdensity lipoprotein-cholesterol in
patientswithHoFH;
 theKYNAMRO label contains aBoxedWarning citing a riskof hepatic toxicity; and
Following approval of a drug, we andour partnersmust complywith comprehensive government regulations regarding the
manufacture,marketing anddistributionof drugproducts. Even if approved, we or our partnersmaynot obtain the labeling claims
necessaryor desirable for successfully commercializing our drugproducts, includingKYNAMRO, ISIS-APOCIIIRx, ISIS-SMNRx and
ISIS-TTRRx.