Isis Pharmaceuticals, Inc. Form 10K - page 7

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In January2013, theFDA approved theNDA forKYNAMRO for use inpatientswithHoFH.
In2012, Genzyme initiated aPhase 3 study titled ‘evaluating the saFety and atherOgeniC lipoprotein redUctionof
mipomerSen inFH, or FOCUSFH. InFOCUSFH, Genzyme is evaluatingKYNAMRO inpatientswith severe heterozygous FH.
SevereHeFHpatients are defined as FHpatientswhohaveLDL-C levels greater than200mg/dLwith coronary arterydisease ormore
than300mg/dLwithout coronary arterydisease despitemaintaining a regimen ofmaximally tolerated lipid-lowering therapy. In this
60-week, placebo-controlled, randomized, double-blind study, KYNAMRO is being administered eitherweekly as a 200mg injection
or three times aweek as a 70mg injection.
Severe&RareDiseaseFranchise
Our severe and rare disease franchise is the largest franchise inour pipeline. We believe that our antisense technology could
offer effective therapies for patientswith severe and rare diseases that are life-threateningor fatal and forwhich there are limited
treatment options. According to theNational Institutes ofHealth, orNIH, there are approximately5,000 to8,000 rare diseases,many
life-threateningor fatal. Unfortunately, patientswithmanyof these severe and rarediseases have few effective therapies available.
Sincemost severe and rare diseases are genetic or have a genetic component, parents oftenpass the disease to their children, creating a
legacy of the disease and resulting inprofound effects on the family.
We are discovering anddeveloping antisense drugs to treat severe and rare diseases forwhich there is a need for new
treatment options. Our partners, Biogen Idec, Roche andGSK, allowus to expandour drugdiscovery anddevelopment efforts
beyondwhatwewould choose todo internally. Due to the severenature of these diseases and the lackof available treatments, there is
anopportunity formore flexible and efficient development paths to themarket. Thismeans that, in some cases, the studies necessary
for us todemonstrate proof-of-conceptwith a particular drugmay also be the studies that complete ourmarketing registration
package, therebyprovidinguswith a relatively rapidpath tomarket for potential new treatments for devastating andoften fatal
diseases.
KYNAMRO (mipomersen sodium) injection — Our flagship product, KYNAMRO, is on themarket in theUnitedStates for
patientswithHoFH. Formore informationonKYNAMRO, see the previousKYNAMRO section, which is directly after our pipeline
table.
Alicaforsen — Under license toAtlanticPharmaceuticals Limited, alicaforsen is an antisense drug that targets intercellular
adhesionmolecule 1, or ICAM-1. ICAM-1 is over-expressed in awide varietyof inflammatorydisorders, including ulcerative colitis
and pouchitis. Ulcerative colitis, orUC, is an inflammatory bowel disease, or IBD, of the colon, a part of the large intestine, and
pouchitis is an inflammation of the surgically constructed internal pouch created inUCpatientswhohave had their diseased colons
removed.
In 2007, we licensed alicaforsen toAtlanticPharmaceuticals for pouchitis, UC andother inflammatory diseases. TheFDA
andEMAhave since granted alicaforsenOrphanDrugDesignation for the treatment of pouchitis in theUnitedStates andEurope,
respectively. Atlantic Pharmaceuticals currently supplies alicaforsen in response tophysicians’ requests under international Named
Patient Supply regulations for patientswithpouchitis andother indications. We are eligible to receive royalties onproduct sales,
including product sales under theNamedPatient Supply fromAtlanticPharmaceuticals. AtlanticPharmaceuticals is currently
pursuingopportunities to fund further development of alicaforsen.
ISIS-TTRRx — ISIS-TTR Rx is an antisense drugwe designed to treat TTR amyloidosis, a severe and rare genetic disease in
which the patient inherits amutant gene that produces amisfolded formof TTR, whichprogressively accumulates in tissues. In
patientswithTTR amyloidosis, both themutant andnormal forms of TTR canbuildup as fibrils in tissues, such as the heart,
peripheral nerves, and the gastrointestinal tract. The presence of TTR fibrils interfereswith the normal functions of these tissues, and
as theTTR protein fibrils enlargemore tissue damage occurs and the diseaseworsens.
There are two common types of TTR amyloidosis, familial amyloid cardiomyopathy, or FAC, which affectsmore than
40,000patientsworldwide, and familial amyloidpolyneuropathy, or FAP, which affectsmore than10,000patientsworldwide.
PatientswithFAC haveTTRbuild up in the heartmuscle and succumb toheart failure approximately five to six years after symptom
onset. PatientswithFAPhaveTTRbuildup inperipheral nerve tissue leading to the loss of nerve function andwasting.
We designed ISIS-TTR Rx to inhibit the productionof all forms of TTR, and tooffer an alternative approach to treat all types
of TTR-related amyloidosis. ISIS-TTRRx is the first drug to enter development under our preferredpartner alliancewithGSK.We
have earned$24million fromGSK as ISIS-TTRRx has advanced indevelopment and are eligible to earn an additional $46million in
pre-licensingmilestone payments to support thePhase 3 studyof ISIS-TTRRx. In addition, we are eligible to earn regulatory and sales
milestone payments fromGSK should ISIS-TTRRx achieve registration andmeet certain sales thresholds.We are also eligible to
receive double-digit royalties on sales of ISIS-TTRRx.