Competition
Our Business in General
For many of their applications, our drugs will compete with existing therapies for market share. In addition,
there are a number of companies pursuing the development of oligonucleotide-based technology and the
development of pharmaceuticals utilizing this technology. These companies include specialized pharmaceutical
firms and large pharmaceutical companies acting either independently or together with biopharmaceutical
companies.
Our products under development address numerous markets. The diseases our drugs target for which we
have or may receive regulatory approval will determine our competition. For some of our products, an important
factor in competition may be the timing of market introduction of competitive products. Accordingly, the relative
speed with which we can develop products, complete the clinical trials and approval processes and supply
commercial quantities of the products to the market are important competitive factors. We expect to compete
among products approved for sale based on a variety of factors, including, among other things, product efficacy,
safety, reliability, availability, price, reimbursement and patent position.
KYNAMRO
In January 2013, the FDAapproved the marketing application for KYNAMRO in the United States for
patients with HoFH. Genzyme has also obtained marketing approval in other countries, includingMexico,
Argentina, South Korea and Peru, and is pursuing marketing approval for KYNAMRO in other countries.
Apheresis and maximally tolerated lipid-lowering therapies, including statins, have been the standard of care for
homozygous FH patients. Apheresis is a two to four hour process administered two to four times a month that
mechanically separates LDL-C from the blood. Because apheresis is an invasive, time-consuming procedure
conducted only in specialty centers, it can be difficult for patients to receive this treatment.
We believe that of the drugs that are in development or on the market, KYNAMRO’s closest competitor is
lomitapide. Lomitapide is a small molecule drug that Aegerion Pharmaceuticals developed and is
commercializing to limit secretion of cholesterol and triglycerides from the intestines and the liver. The FDAand
EMAhave approved lomitapide as an oral, once-a-day treatment for patients with HoFH. The FDAapproval for
lomitapide is supported by a Phase 3 study in 29 patients with HoFH. Aegerion states that the most common
adverse reactions in the Phase 3 study were gastrointestinal, reported by 27 of 29 patients, or 93%. In earlier
studies evaluating lomitapide, patients discontinued use of lomitapide at a high rate due to gastrointestinal
adverse events, such as diarrhea, nausea and vomiting. In addition, some patients experienced elevations in liver
enzymes and increased mean levels of fat in the liver, or hepatic fat, both of whichAegerion states it observed in
its Phase 3 clinical trial of lomitapide. Like KYNAMRO, lomitapide is available only through a REMS program
that restricts the access of lomitapide to only patients with a clinical or laboratory diagnosis consistent with
HoFH and both the KYNAMRO and lomitapide labels contain a BoxedWarning citing the risk of liver toxicity.
In our clinical experience with KYNAMRO, we have seen substantial reductions in LDL-C and reductions
in other atherogenic lipids linked to cardiovascular disease. In our Phase 3 studies that evaluated KYNAMRO in
more than 250 patients, the most common adverse events patients observed were injection site reactions and
flu-like symptoms. We also observed elevations in liver transaminases and moderate median increases in liver fat
that appeared to be associated with greater reductions in apoB. Patients administer KYNAMRO by injection once
weekly at home with a prefilled syringe while patients take lomitapide orally once daily. To avoid gastrointestinal
events, patients on lomitapide are required to maintain a low fat diet of less than 20% fat and patients are
gradually titrated to a maximally tolerated dose. In the lomitapide label, concurrent use of lomitapide and
common medications for HoFH patients who have cardiovascular disease, including simvastatin and warfarin,
need to be closely monitored due to drug-drug interactions with potentially harmful outcomes. KYNAMRO has
no restrictions with these medications or diet restrictions, which may be advantageous for HoFH patients who are
on a broad range of therapies due to the severity of their disease. KYNAMRO sales could be affected if
KYNAMRO’s product profile is not advantageous when compared to an oral drug, as some patients may prefer
the oral drug over KYNAMRO. Factors affecting a product’s profile may include, efficacy, side effects, pricing
and reimbursement.
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