200 mg of KYNAMRO and 129 patients received placebo for a median treatment duration of 25 weeks. Eighteen
percent of patients on KYNAMRO and two percent of patients on placebo discontinued treatment due to adverse
reactions. The most common adverse reactions in patients treated with KYNAMRO that led to treatment
discontinuation and occurred at a rate greater than placebo were: injection site reactions of five percent, alanine
aminotransferase increase of 3.4 percent, flu-like symptoms of 2.7 percent, aspartate aminotransferase increase of
2.3 percent and abnormal liver function test of 1.5 percent.
In January 2013, the FDAapproved the NewDrugApplication, or NDA, for KYNAMRO for use in patients
with HoFH.
In 2012, Genzyme initiated a Phase 3 study titled ‘‘evaluating the saFety and atherOgeniC lipoprotein
redUction of mipomerSen in FH’’, or FOCUS FH. In FOCUS FH, Genzyme is evaluating KYNAMRO in
patients with severe heterozygous FH. Severe HeFH patients are defined as FH patients who have LDL-C levels
greater than 200 mg/dLwith coronary artery disease or more than 300 mg/dLwithout coronary artery disease
despite maintaining a regimen of maximally tolerated lipid-lowering therapy. In this 60-week, placebo-controlled,
randomized, double-blind study, KYNAMRO is being administered either weekly as a 200 mg injection or three
times a week as a 70 mg injection. Genzyme has completed enrollment in this study and plans to have data in
the middle of 2015.
Severe &Rare Disease Franchise
Our severe and rare disease franchise is the largest franchise in our pipeline. We believe that our antisense
technology could offer effective therapies for patients with severe and rare diseases and neurological disorders
that are life-threatening or fatal and for which there are limited treatment options. According to the National
Institutes of Health, or NIH, there are approximately 5,000 to 8,000 rare diseases, many life-threatening or fatal.
Unfortunately, patients with many of these severe and rare diseases have few effective therapies available. Since
most severe and rare diseases are genetic or have a genetic component, parents often pass the disease to their
children, creating a legacy of the disease and resulting in profound effects on the family. ISIS-SMN
Rx
, the most
advanced neurological drug in our pipeline, is now in two Phase 3 studies for the treatment of infants and
children with SMA.
We are discovering and developing antisense drugs to treat severe and rare and neurological diseases for
which there is a need for new treatment options. We have established strategic alliances in drug development
areas that are high risk or in which our partners have significant expertise and resources to allow us to expand
our drug discovery and development efforts beyond what we would choose to do internally. For example, our
strategic partnerships with Biogen Idec and Roche have supported advancing five drugs for the treatment of
neuromuscular or neurological diseases in our pipeline.
Due to the severe nature of these diseases and the lack of available treatments, there is an opportunity for
more flexible and efficient development paths to the market. This means that, in some cases, the studies
necessary for us to demonstrate proof-of-concept with a particular drug may also be the studies that complete our
marketing registration package, thereby providing us with a relatively rapid path to market for potential new
treatments for devastating and often fatal diseases.
KYNAMRO (mipomersen sodium) injection
—
Our flagship product, KYNAMRO, is on the market in the
United States for patients with HoFH. For more information on KYNAMRO, see the previous KYNAMRO
section, which is directly after our pipeline table.
Alicaforsen
—
Atlantic Pharmaceuticals Limited is developing and selling alicaforsen through a named
patient program. Anamed patient program allows Atlantic to sell alicaforsen in response to physicians’ requests
under international named patient supply regulations for patients with pouchitis and other indications. Alicaforsen
is an antisense drug designed to target the intercellular adhesion molecule 1, or ICAM-1. ICAM-1 is
over-expressed in a wide variety of inflammatory disorders, including ulcerative colitis and pouchitis. Ulcerative
colitis, or UC, 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 in UC patients who have had their
diseased colons removed.
In 2007, we licensed alicaforsen toAtlantic Pharmaceuticals for pouchitis, UC and other inflammatory
diseases. The FDAand EuropeanMedicines Agency, or EMA, have since granted alicaforsen Orphan Drug
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