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Failure to receivemarketing approval for our drugs, includingKYNAMROoutside theUnitedStates or initial approvals for
ISIS-APOCIII
Rx
, ISIS-SMN
Rx
and ISIS-TTR
Rx
, or delays in these approvals couldprevent or delay commercial introductionof the
drug, and, as a result, couldnegatively impact our ability to generate revenue fromproduct sales.
If the results of clinical testing indicate that anyof ourdrugs are not suitable for commercial usewemayneed toabandon one
ormore of our drugdevelopment programs.
Drugdiscovery anddevelopment has inherent risks and the historical failure rate for drugs is high. Antisense drugs are a
relatively new approach to therapeutics. Ifwe cannot demonstrate that our drugs are safe and effective for human use, wemay need to
abandonone ormore of our drugdevelopment programs. There are ongoing clinical studies forKYNAMRO and sales topatients,
adverse events fromwhich couldnegatively impact our pendingor plannedmarketing approval applications and commercializationof
KYNAMRO.
In the past, we have invested in clinical studies of drugs that have notmet the primary clinical endpoints in their Phase 3
studies. Similar results couldoccur in any additional clinical studies forKYNAMRO and in clinical studies for our other drugs,
including ISIS-APOCIII
Rx
, ISIS-SMN
Rx
and ISIS-TTR
Rx
. If anyof our drugs in clinical studies, includingKYNAMRO, ISIS-
APOCIII
Rx
, ISIS-SMN
Rx
and ISIS-TTR
Rx
, does not show sufficient efficacy in patientswith the targeted indication, it couldnegatively
impact our development and commercializationgoals for the drug andour stockprice could decline.
Even if our drugs are successful inpreclinical andhuman clinical studies, thedrugsmaynot be successful in late-stage clinical
studies.
Successful results inpreclinical or initial human clinical studies, including thePhase 3 results forKYNAMRO and thePhase
2 results for some of our other drugs indevelopment,may not predict the results of subsequent clinical studies, including subsequent
studies ofKYNAMRO and thePhase 3 studies for ISIS-APOCIII
Rx
, ISIS-SMN
Rx
and ISIS-TTR
Rx
. There are a number of factors that
could cause a clinical study to fail or be delayed, including:
the clinical studymayproduce negative or inconclusive results;
regulatorsmay require thatwe hold, suspendor terminate clinical research for noncompliancewith regulatory
requirements;
we, our partners, the FDAor foreign regulatory authorities could suspendor terminate a clinical studydue to adverse
side effects of a drugon subjects in the trial;
wemaydecide, or regulatorsmay require us, to conduct additional preclinical testing or clinical studies;
enrollment in our clinical studiesmaybe slower thanwe anticipate;
the cost of our clinical studiesmaybe greater thanwe anticipate; and
the supply or quality of our drugs or othermaterials necessary to conduct our clinical studiesmay be insufficient,
inadequate or delayed.
Any failure or delay in the clinical studies, including any further studies under the development program forKYNAMRO and
thePhase 3 studies for ISIS-APOCIII
Rx
, ISIS-SMN
Rx
and ISIS-TTR
Rx
, could reduce the commercial potential or viabilityof our drugs.
Ifwe cannotmanufacture ourdrugs or contractwitha thirdparty tomanufacture ourdrugs at costs that allowus to charge
competitiveprices tobuyers, we cannotmarket ourproducts profitably.
To successfully commercialize anyof our drugs, we or our partnerwouldneed to establish large-scale commercial
manufacturing capabilities either onour ownor through a thirdpartymanufacturer. In addition, as our drugdevelopment pipeline
increases andmatures, wewill have a greater need for clinical trial and commercialmanufacturing capacity.We have limited
experiencemanufacturingpharmaceutical products of the chemical class representedbyour drugs, calledoligonucleotides, on a
commercial scale for the systemic administrationof a drug. There are a small number of suppliers for certain capital equipment and
rawmaterials thatwe use tomanufacture our drugs, and some of these supplierswill need to increase their scale of production tomeet
our projectedneeds for commercialmanufacturing. Further, wemust continue to improve ourmanufacturingprocesses to allowus to
reduce our drug costs. Wemay not be able tomanufacture our drugs at a cost or inquantities necessary tomake commercially
successful products.
