Isis Pharmaceuticals, Inc.
) recently announced the initiation of a phase I study on an
antisense candidate targeting apolipoprotein(a), ISIS-APOA, for
treating patients suffering from atherosclerosis .
We note that apolipoprotein(a) helps in the formation of plaque
in arteries through its attachment to an LDL-C particle in a
complex known as lipoprotein(a) or Lp(a). Elevated levels of
Lp(a) are associated with an increased risk of cardiovascular
events such as atherosclerosis, coronary heart disease, heart
attack and stroke.
ISIS-APOA aims to bring down Lp(a) levels by inhibiting
The blind, placebo-controlled, dose-escalation phase I study will
enroll approximately 56 healthy volunteers and assess safety,
tolerability and pharmacokinetics of ISIS-APOA (both single and
Earlier this month, Isis Pharma published encouraging data in the
journal Circulation Research related to antisense technology. It
was found that antisense targeting of apolipoprotein C-III
(apoC-III) showed significant decline in apoC-III and
triglycerides. Both apoC-III and triglycerides, are risk factors
associated with cardiovascular diseases.
We are impressed by the development of antisense technology and
believe that the number of potential therapeutic applications is
enormous. Antisense drugs may have significant potential to treat
a number of diseases where small molecules and biologic compounds
Although still in its early stage, antisense technology with
mechanisms such as small interfering RNA (siRNA), RNA
interference (RNAi), alternate splicing, and microRNA (mRNA) have
the potential to change how diseases are treated.
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We note that Isis Pharma's lead product, Kynamro (mipomersen
sodium), received FDA approval in Jan 2013 for the treatment of
familial hypercholesterolemia (FH). Isis Pharma's partner
) is marketing the product in the US. Sanofi is also looking to
get the drug approved in the rest of the world including Europe.
Isis Pharma currently carries a Zacks Rank #3 (Hold). Meanwhile,
stocks such as
Osiris Therapeutics, Inc.
) carry a Zacks Rank #1 (Strong Buy) and are worth