Isis Reports Phase 2 Data on ISIS-APOCIII Rx Showing Significant Reductions in Triglycerides and APOC-III in Patients with High

Isis Reports Phase 2 Data on ISIS-APOCIII Rx Showing Significant Reductions in
  Triglycerides and APOC-III in Patients with High Triglycerides and Type 2

Improvements in glucose control and insulin sensitivity also observed

Conference call webcast and slide presentation Monday, June 24, 8:30 a.m. ET

PR Newswire

CARLSBAD, Calif., June 23, 2013

CARLSBAD, Calif., June 23, 2013 /PRNewswire/ --Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced that data from the Phase 2 study of ISIS-APOCIII[Rx]
in patients with high triglycerides and type 2 diabetes were presented today
at the American Diabetes Association Scientific Sessions in Chicago. In this
study, patients treated with ISIS-APOCIII[Rx] experienced an 88 percent
reduction in apolipoprotein C-III (apoC-III), a 72 percent reduction in
triglyceride levels, a 40 percent increase in high-density lipoprotein
cholesterol (HDL-C), the 'good' cholesterol, and improvements in other
atherogenic lipid parameters. In addition, patients dosed with
ISIS-APOCIII[Rx] showed consistent trends toward enhanced insulin sensitivity
with improvements in multiple measures of glucose control.Isis is also
evaluating ISIS-APOCIII[Rx] in a separate Phase 2 study in patients with
moderate to severe high triglycerides and plans to report data from this study
this summer.

"Patients with high levels of triglycerides are at a significant risk for
cardiovascular disease and stroke.Because high triglyceride levels are also
associated with obesity and insulin insensitivity, reducing apoC-III and
triglycerides in high-risk patients, like type 2 diabetic patients, may lead
to improved insulin sensitivity and improvement of metabolic syndrome," said
Joseph L. Witztum, M.D., professor of medicine, University of California, San
Diego."The data presented today on ISIS-APOCIII[Rx] are very encouraging and
unique in that there is a significant and substantial reduction in both
apoC-III and triglyceride levels with a significant increase in HDL and
improvements across the board in the overall lipid parameters, including
non-HDL-C. In addition, unlike many available triglyceride-lowering therapies,
including diet, ISIS-APOCIII[Rx] did not raise LDL-C in these patients. There
is no other drug in development that demonstrates the potential for such a
broad therapeutic profile. The dramatic effect of ISIS-APOCIII[Rx] on all of
these parameters could translate into significant benefit to many patients,
including patients with high triglycerides and type 2 diabetes."

The Phase 2 study of ISIS-APOCIII[Rx] was a blinded, randomized,
placebo-controlled 13-week study designed to assess the safety and activity of
ISIS-APOCIII[Rx] in patients with high triglycerides levels (between 200 and
500 mg/dL) and type 2 diabetes. After only 13 weeks of dosing, robust and
prolonged, statistically significant mean reductions of 88 percent from
baseline in apoC-III levels (p<0.03) and 72 percent from baseline in fasting
plasma triglyceride levels (p<0.03) were observed. All treated patients
achieved triglyceride levels of less than 100 mg/dL by four weeks of dosing,
and the average triglyceride level was 71 mg/dL at the end of treatment.
Furthermore, patients treated with ISIS-APOCIII[Rx] demonstrated a rapid,
prolonged and statistically significant mean increase in HDL-C of 40 percent
from baseline (p<0.03) with improvements in overall lipid parameters,
including non-HDL-C and VLDL-C, and no increase in LDL-C.

In addition, consistent improvements in HbA1c and other measures of glucose
control, including serum fructosamine and glycated albumin, were observed in
patients dosed with ISIS-APOCIII[Rx].The effects of ISIS-APOCIII[Rx] observed
on measures of glucose control were in addition to those achieved with each
patient's existing therapeutic regimen of metformin. Improvements in
indicators of insulin sensitivity were also observed in patients suggesting
that inhibition of apoC-III could improve insulin sensitivity in patients with
high triglycerides and type 2 diabetes. ISIS-APOCIII[Rx] demonstrated a good
safety profile in the study and was well tolerated in all subjects with no
discontinuations, no clinically meaningful elevations in liver enzymes, no
flu-like symptoms, no significant adverse events, and a low incidence of mild
injection site reactions which were infrequent and typically resolved within a
day or two.

"Our focus is to bring ISIS-APOCIII[Rx] to the market for patients with severe
hypertriglyceridemia. These are patients who cannot reduce their
triglycerides to safe levels with currently available medicines. We plan to
report data from our ongoing Phase 2 program in very high triglyceride
patients later this summer evaluating ISIS-APOCIII[Rx] in combination with
fibrates and as a monotherapy," said Richard Geary, Ph.D., senior vice
president of clinical development at Isis. "In the study we are reporting
today, we observed rapid and prolonged reductions of apoC-III, triglycerides
and other lipid parameters, as well as improvements in glucose control and
insulin sensitivity. These data suggest that ISIS-APOCIII[Rx] could provide
therapeutic benefit to patients with high triglycerides who are insulin
insensitive, including patients who are obese or have type 2 diabetes. In
addition, the positive effect of ISIS-APOCIII[Rx] on all atherogenic lipid
parameters measured and the observed increase in HDL, significantly enhances
the potential profile of the drug."

In this study, 11 patients were randomized 2:1 to receive a 300 mg dose of
ISIS-APOCIII[Rx] or placebo via weekly subcutaneous injections for 13 weeks.
Patients entering the study had a mean apoC-III level of 14.3 mg/dL, a mean
triglyceride level of 259 mg/dL and a mean HDL level of 43.4 mg/dL.

ISIS-APOCIII[Rx] is an antisense drug that targets apoC-III, a gene produced
in the liver that plays a central role in the regulation of serum
triglycerides. Humans who do not produce apoC-III have lower levels of
triglycerides and lower instances of cardiovascular disease. In clinical
studies, patients with lower levels of apoC-III and triglycerides exhibit
lower cardiovascular event rates. Humans with elevated levels of ApoC-III have
increased dyslipidemia associated with multiple metabolic abnormalities, such
as insulin resistance and/or metabolic syndrome. In addition, the prevalence
of type 2 diabetes is increased in patients with elevated triglycerides.

Conference Call
At 8:30 a.m. Eastern Time tomorrow, June 24, 2013, Isis will conduct a live
webcast and slide presentation conference call to discuss the positive Phase 2
data presented today at the American Diabetes Association. Interested parties
may listen to the call by dialing 866-652-5200, or access the webcast with or
without audio at A webcast replay will be available for a
limited time at the same address.

Isis is exploiting its leadership position in antisense technology to discover
and develop novel drugs for its product pipeline and for its partners. Isis'
broad pipeline consists of 28 drugs to treat a wide variety of diseases with
an emphasis on cardiovascular, metabolic, severe and rare diseases, and
cancer. Isis' partner, Genzyme, is commercializing Isis' lead product,
KYNAMRO™, in the United States for the treatment of patients with HoFH.
Genzyme is also pursuing marketing approval of KYNAMRO in other markets.
Isis' patents provide strong and extensive protection for its drugs and
technology. Additional information about Isis is available at

This press release includes forward-looking statements regarding the
discovery, development, and potential of drugs for cardiovascular diseases,
and the development, activity, therapeutic potential and safety of
ISIS-APOCIII[Rx]. Any statement describing Isis' goals, expectations,
financial or other projections, intentions or beliefs, including the
commercial potential of KYNAMRO, is a forward-looking statement and should be
considered an at-risk statement. Such statements are subject to certain risks
and uncertainties, particularly those inherent in the process of discovering,
developing and commercializing drugs that are safe and effective for use as
human therapeutics, and in the endeavor of building a business around such
drugs. Isis' forward-looking statements also involve assumptions that, if
they never materialize or prove correct, could cause its results to differ
materially from those expressed or implied by such forward-looking
statements. Although Isis' forward-looking statements reflect the good faith
judgment of its management, these statements are based only on facts and
factors currently known by Isis. As a result, you are cautioned not to rely
on these forward-looking statements. These and other risks concerning Isis'
programs are described in additional detail in Isis' annual report on Form
10-K for the year ended December 31, 2012 and its most recent quarterly report
on Form 10-Q, which are on file with the SEC. Copies of these and other
documents are available from the Company.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.
KYNAMRO™ is a trademark of Genzyme Corporation.

SOURCE Isis Pharmaceuticals, Inc.

Contact: D. Wade Walke, Ph.D., Executive Director, Corporate Communications
and Investor Relations, +1-760-603-2741, Amy Blackley, Ph.D., Associate
Director, Corporate Communications, +1-760-603-2772
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