The FDAand foreign regulatory authorities have the authority to impose significant restrictions on an
approved drug product through the product label and on advertising, promotional and distribution activities. For
example:
•
KYNAMRO is approved in the United States as an adjunct to lipid-lowering medications and diet to
reduce low density lipoprotein-cholesterol, apolipoprotein B, total cholesterol, and non-high density
lipoprotein-cholesterol in patients with HoFH;
•
the KYNAMRO label contains a BoxedWarning citing a risk of hepatic toxicity; and
•
KYNAMRO is available only through a Risk Evaluation andMitigation Strategy called the
KYNAMROREMS.
In addition, when approved, the FDAor a foreign regulatory authority may condition approval on the
performance of post-approval clinical studies or patient monitoring, which could be time consuming and
expensive. If the results of such post-marketing studies are not satisfactory, the FDAor a foreign regulatory
authority may withdrawmarketing authorization or may condition continued marketing on commitments from us
or our partners that may be expensive and/or time consuming to fulfill.
If we or others identify side effects after any of our drug products are on the market, or if manufacturing
problems occur subsequent to regulatory approval, we or our partners may lose regulatory approval, or we or our
partners may need to conduct additional clinical studies and/or change the labeling of our drug products
including KYNAMRO, ISIS-APOCIII
Rx
, ISIS-SMN
Rx
and ISIS-TTR
Rx
.
We depend on our collaboration withGenzyme for the development and commercialization of
KYNAMRO.
We have entered into a collaborative arrangement with Genzyme to develop and commercialize
KYNAMRO.
We entered into this collaboration primarily to:
•
fund some of our development activities for KYNAMRO;
•
seek and obtain regulatory approvals for KYNAMRO; and
•
successfully commercialize KYNAMRO.
In general, we cannot control the amount and timing of resources that Genzyme devotes to our
collaboration. If Genzyme fails to further develop and commercialize KYNAMRO, or if Genzyme’s efforts are
not effective, our business may be negatively affected. We are relying on Genzyme to obtain additional
marketing approvals for and successfully commercialize KYNAMRO. Our collaboration with Genzyme may not
continue or result in the successful commercialization of KYNAMRO. Genzyme can terminate our collaboration
at any time. If Genzyme stopped developing or commercializing KYNAMRO, we would have to seek additional
sources for funding and may have to delay or reduce our development and commercialization programs for
KYNAMRO. If Genzyme does not successfully commercialize KYNAMRO, we may receive limited or no
revenues for KYNAMRO. In addition, Sanofi’s acquisition of Genzyme could disrupt Genzyme or distract it
from performing its obligations under our collaboration.
If Genzyme cannot manufacture finished drug product for KYNAMRO or the post-launch supply of the
active drug substance for KYNAMRO, KYNAMROmay not achieve ormaintain commercial success.
We rely on Genzyme to manufacture the finished drug product for KYNAMRO and the long term supply of
KYNAMRO drug substance. Genzyme may not be able to reliably manufacture KYNAMRO drug substance and
drug product to support the long term commercialization of KYNAMRO. If Genzyme cannot reliably
manufacture KYNAMRO drug substance and drug product, KYNAMROmay not achieve or maintain
commercial success, which will harm our ability to generate revenue.
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