Aegerion has stated that it is charging in excess of $300,000 for lomitapide per patient per year, which is
higher than KYNAMRO. Our partner, Genzyme, a Sanofi Company, has extensive experience in bringing
medicines to patients with severe and rare diseases. In the United States, Genzyme intends to capitalize on its
existing sales and marketing infrastructure within specialized medical communities. In addition, with an existing
global commercial infrastructure in the cardiovascular community, we believe that Sanofi and its global presence
will aid in the expansion of KYNAMRO into markets throughout the world.
ISIS-TTR
Rx
In February 2013, we began a Phase 3 study evaluating ISIS-TTR
Rx
in patients with FAP, a severe and rare
disease. Patients with FAP have very limited therapeutic options and liver transplantation is the most common
treatment used to reduce the production of the plaque-causing protein. Liver transplantation is a very complicated
and expensive medical procedure performed only in major medical centers. Patients who receive a liver
transplant are often required to take immunosuppressive drugs for the rest of their lives. In addition, due to the
previous accumulation of plaques in nerve and heart muscle, normal TTR protein from a normal liver can still
aggregate and progress the disease.
We believe that of the drugs that are in development or on the market, ISIS-TTR
Rx
’s closest competitor is
patisiran, an intravenously administered RNAi molecule being developed byAlnylam. Patisiran is also designed
to inhibit the production of TTR protein by reducing TTRmRNA. As such, patisiran and ISIS-TTR
Rx
are
designed to employ similar mechanisms of action to reduce the disease-causing TTR protein accumulation. In
early clinical studies, both drugs produced similar TTRmRNA reduction in treated subjects. In November 2013,
Alnylam startedAPOLLO, a Phase 3 program in patients with FAP. We believe that because we initiated the
Phase 3 study for ISIS-TTR
Rx
approximately ten months earlier than theAPOLLO study, ISIS-TTR
Rx
will be the
first RNA-targeted drug on the market. If Alnylam’s drug candidate is successful in clinical studies and receives
marketing approval, it could compete with ISIS-TTR
Rx
. Tafamadis, an oral drug approved and launched in
Europe, Japan andArgentina and approved inMexico under the brand name Vyndaqel, is another competitor to
ISIS-TTR
Rx
. InMay 2012, the FDA rejected tafamadis for use in the United States stating that the Phase 3 study
data did not show that tafamadis is effective in directly slowing the progression of FAP. We believe that based on
the mechanism of our drug and our preclinical data, that ISIS-TTR
Rx
could have a significantly better therapeutic
profile than tafamadis and other drugs that are earlier in development. Another oral drug, diflunisal, has been
shown to stabilize the TTR tetramer structure and could also offer benefit to patients with TTR amyloidosis.
Diflunisal is an oral generic drug that is available in the United States and Europe for use as a non-steroidal
anti-inflammatory drug. Diflunisal was tested in a Phase 3 study in patients with FAP. In this study more than
half of the patients discontinued treatment and although a clinically meaningful change in disease progression
was measured, all patients continued to progress in their disease. If diflunisal is successful in receiving marketing
approval for TTR amyloidosis, or if prescribed to TTR patients, it could compete with ISIS-TTR
Rx
.
ISIS-APOCIII
Rx
We have completed a broad Phase 2 program on our novel triglyceride-lowering drug, ISIS-APOCIII
Rx
, and
we initiated a Phase 3 program on this drug in the third quarter of 2014. Based on our Phase 2 data, we believe
that ISIS-APOCIII
Rx
will work equally well as a single agent or in combination with other triglyceride-lowering
drugs on the market. As such, we do not intend to displace any existing therapy with ISIS-APOCIII
Rx
.
We believe that of the drugs that are in development or on the market, ISIS-APOCIII
Rx
’s closest competitor
is the gene therapy treatment Glybera, which is only marketed in Europe. As of December 31, 2014, Glybera had
not been approved by the FDA. Glybera was approved by the European Commission in October 2012 as a
treatment for adult patients diagnosed with familial lipoprotein lipase deficiency, or LPLD, confirmed by genetic
testing, and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. Glybera is being
marketed by Chiesi, a partner of UniQure. The European Commission approval was supported by three
interventional clinical studies in 27 patients with LPLD. Glybera was well tolerated in these studies, with no
relevant safety issues observed. Results of these studies indicated that a single dose administration of Glybera
resulted in long-term biological activity of the LPL protein. Chiesi announced that they are seeking a retail price
of EUR 53,000 ($65,625) per vial, or about EUR 1.1 million ($1.4 million) per year for Glybera for a patient
weighing 62.5kg. This makes Glybera the most expensive rare disease drug in the world. If approved in Europe,
ISIS-APOCIII
Rx
could compete with Glybera in the European Union and if Glybera is successful in obtaining
marketing approval in the United States, it could compete with ISIS-APOCIII
Rx
in the United States. Another
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