Press Releases
Genzyme and Isis Present KYNAMRO® Clinical Data at the American Heart Association
CAMBRIDGE, Mass. &
Genzyme, a
“This analysis is very encouraging as the rate of MACE declined sevenfold
after two years of treatment with KYNAMRO in patients with homozygous and
heterozygous familial hypercholesterolemia (FH),” said Dr.
This retrospective analysis included 104 patients who enrolled in the long-term extension study of KYNAMRO after having completed one of the KYNAMRO phase 3 blinded, randomized, placebo-controlled 6-month trials in patients with homozygous and heterozygous FH. All patients who completed at least two years of treatment with KYNAMRO were included in the analysis. The rate of MACE in patients treated with KYNAMRO for two years were adjudicated by an independent committee and compared to the rate of MACE in the same patients based on their medical history prior to treatment with KYNAMRO.
In this analysis, MACE were identified in 62% of patients during two years prior to KYNAMRO treatment, and 9% of patients during a mean of 24.4 months after initiation of treatment with KYNAMRO. MACE were defined as myocardial infarction (MI), stroke, unstable angina (UA) and revascularization procedures (PCI/CABG).
Event |
Number of MACE in |
Number of MACE in | ||||
MI | 39 | 2 | ||||
PCI/CABG | 99 | 6 | ||||
UA | 5 | 4 | ||||
Stroke | 3 | 0 | ||||
Total | 146 | 12 | ||||
MACE rate
(per 1000 patient-months) p<0.0001 |
25.7* | 3.6* | ||||
The marked reduction in MACE coincided with the absolute mean reductions in LDL cholesterol levels (-49 to -113 mg/dL) reported for the phase 3 FH clinical trials.
"Patients with homozygous FH have extreme cholesterol levels and are at
significant risk for cardiovascular events. KYNAMRO is approved for use in these
patients in the U.S. to reduce LDL-cholesterol, apoB, total cholesterol and
non-HDL cholesterol as an adjunct to lipid lowering medication and diet. The
data presented today are encouraging and add to the broad lipid lowering profile
observed in these patients,” said Dr.
KYNAMRO contains a Boxed Warning citing the risk of hepatic toxicity. Patients taking KYNAMRO should have liver enzyme testing before starting the drug and periodically thereafter. See below for Important Safety Information about KYNAMRO.
The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.
Because of the risk of hepatotoxicity, KYNAMRO is available only through a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. The goals of the KYNAMRO REMS are:
- To educate prescribers about the risk of hepatotoxicity associated with the use of KYNAMRO, and the need to monitor patients during treatment with KYNAMRO as per product labeling.
- To restrict access to therapy with KYNAMRO to patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia (HoFH).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF HEPATOTOXICITY
KYNAMRO can cause elevations in transaminases. In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT).
KYNAMRO also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of KYNAMRO if the ALT or AST are ≥3x ULN. Discontinue KYNAMRO for clinically significant liver toxicity.
Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS.
CONTRAINDICATIONS
KYNAMRO is contraindicated in the following conditions:
- Moderate or severe hepatic impairment (Child-Pugh B or C) or active liver disease, including unexplained persistent elevations of serum transaminases.
- Patients with a known hypersensitivity to any component of this product.
WARNINGS AND PRECAUTIONS
KYNAMRO can cause elevations in transaminases and hepatic steatosis.
Prior to initiation of treatment with KYNAMRO, measure a full liver panel to include ALT, AST, total bilirubin, and alkaline phosphatase. If the baseline liver-related tests are abnormal, consider initiating KYNAMRO after an appropriate work-up and the baseline abnormalities are explained or resolved.
During the first year, conduct liver-related tests monthly (ALT and AST, at a minimum).
After the first year, conduct these tests at least every 3 months. Discontinue KYNAMRO for persistent or clinically significant elevations.
If transaminase elevations are accompanied by clinical symptoms of liver injury (e.g., nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin ≥2x ULN, or active liver disease, discontinue treatment with KYNAMRO and identify the probable cause.
Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. It is recommended that patients taking KYNAMRO should consume no more than one alcoholic drink per day.
Caution should be exercised when KYNAMRO is used with other medications known to have potential for hepatotoxicity, for example isotretinoin, amiodarone, acetaminophen (>4 g/day for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen. The effect of concomitant administration of KYNAMRO with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
KYNAMRO has not been studied concomitantly with other LDL-lowering agents that can also increase hepatic fat. Therefore, the combined use of such agents is not recommended.
Injection site reactions have been reported in 84% of patients receiving KYNAMRO therapy. These local reactions typically consist of one or more of the following: erythema, pain, tenderness, pruritus and local swelling. To minimize the potential for injection site reactions, proper technique for subcutaneous administration should be followed. Injection site reactions do not occur with all injections but resulted in discontinuation of therapy in 5% of patients in pooled Phase 3 trials.
Flu-like symptoms have been reported in 30% of patients receiving KYNAMRO therapy and include one or more of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue. Flu-like symptoms, which typically occur within 2 days after an injection, do not occur with all injections but resulted in discontinuation of therapy in 3% of patients in pooled Phase 3 trials.
USE IN SPECIFIC POPULATIONS
Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. KYNAMRO should be used during pregnancy only if clearly needed.
Nursing Mothers: It is not known whether KYNAMRO is excreted in human milk. Because many drugs are excreted in human milk a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
Females of Reproductive Potential: KYNAMRO may cause fetal harm. Females who become pregnant during KYNAMRO therapy should notify their healthcare provider. Females of reproductive potential should use effective contraception during KYNAMRO therapy.
Renal Impairment: The safety and efficacy of KYNAMRO treatment in patients with known renal impairment or in patients undergoing renal dialysis have not been established. Due to the lack of clinical data and KYNAMRO’s renal safety profile, KYNAMRO is not recommended in patients with severe renal impairment, clinically significant proteinuria, or on renal dialysis.
ADVERSE REACTIONS
In clinical trials the most commonly-reported adverse reactions were injection site reactions (84%), flu-like symptoms (30%), nausea (14%), headache (12%), and elevations in serum transaminases, specifically ALT (10%).
See full Prescribing Information and Medication Guide, including Boxed Warning, for more details.
About KYNAMRO® (mipomersen sodium) injection
KYNAMRO is indicated
as a first-in-class, oligonucleotide inhibitor, of apolipoprotein B-100
synthesis. KYNAMRO is an adjunct to lipid-lowering medications and diet to
reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B),
total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C)
in patients with homozygous familial hypercholesterolemia (HoFH). KYNAMRO
reduces LDL-C by preventing the formation of atherogenic lipoproteins, the
particles that carry cholesterol through the bloodstream. KYNAMRO acts by
blocking the production of apo B, the protein that provides the structural core
for these atherogenic particles, including LDL. For more information, please
visit www.kynamro.com.
About Homozygous Familial Hypercholesterolemia (HoFH)
HoFH is a
rare genetic disease characterized by extreme cholesterol levels. People with
HoFH have inherited mutations that limit the body’s ability to clear
cholesterol. HoFH is extremely rare. As with other rare diseases, the true
prevalence of HoFH may be underestimated because of inadequate data and
under-diagnosis. Today, it is estimated that HoFH affects about 44,000 people
globally. Medical literature includes different criteria for marking an HoFH
diagnosis. HoFH may be diagnosed by clinical or genetic parameters, and may be
considered in cases of unusually high LDL-C. Because HoFH is genetic, it is
important that all family members of people with HoFH know their cholesterol
levels, regardless of their age.
About Genzyme, a
Genzyme has pioneered
the development and delivery of transformative therapies for patients affected
by rare and debilitating diseases for over 30 years. We accomplish our goals
through world-class research and with the compassion and commitment of our
employees. With a focus on rare diseases and multiple sclerosis, we are
dedicated to making a positive impact on the lives of the patients and families
we serve. That goal guides and inspires us every day. Genzyme’s portfolio of
transformative therapies, which are marketed in countries around the world,
represents groundbreaking and life-saving advances in medicine. As a
About
About
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 34 drugs to
treat a wide variety of diseases with an emphasis on cardiovascular, metabolic,
severe and rare diseases, including neurological disorders, and cancer. Isis’
partner, Genzyme, is commercializing Isis’ lead product, KYNAMRO®, in
Genzyme® and KYNAMRO® are registered trademarks of
Sanofi Forward Looking Statements
This press release
contains forward-looking statements as defined in the Private Securities
Litigation Reform Act of 1995, as amended. Forward-looking statements are
statements that are not historical facts. These statements include projections
and estimates and their underlying assumptions, statements regarding plans,
objectives, intentions and expectations with respect to future financial
results, events, operations, services, product development and potential, and
statements regarding future performance. Forward-looking statements are
generally identified by the words “expects”, “anticipates”, “believes”,
“intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s
management believes that the expectations reflected in such forward-looking
statements are reasonable, investors are cautioned that forwardlooking
information and statements are subject to various risks and uncertainties, many
of which are difficult to predict and generally beyond the control of
Isis Forward Looking Statement
This press release
includes forward-looking statements regarding the development, activity,
therapeutic benefit, safety and commercial potential of KYNAMRO in treating
patients with homozygous FH. Any statement describing
Isis’ goals, expectations, financial or other projections, intentions or beliefs
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
In this press release, unless the context requires otherwise, “Isis,”
“Company,” “we,” “our,” and “us” refers to
Source: Genzyme
Genzyme Media Relations
Lori Gorski, 617-768-9344
lori.gorski@genzyme.com
or
Isis
Media Relations
Amy Blackley, Ph.D., 760-603-2772
ABlackley@isisph.com
or
Isis
Investor Relations
D. Wade Walke, Ph.D., 760-603-2741
WWalke@isisph.com