|[January 29, 2013]
Genzyme and Isis Announce FDA Approval of KYNAMRO™ (mipomersen sodium) Injection for the Treatment of Homozygous Familial Hypercholesterolemia
CAMBRIDGE, Mass. & CARLSBAD, Calif. --(Business Wire)--
Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), and Isis
Pharmaceuticals Inc. (NASDAQ: ISIS), today announced that the U.S. Food
and Drug Administration (FDA) has approved its New Drug Application
(NDA) for KYNAMROTM (mipomersen sodium) injection. KYNAMRO,
given as a 200 mg weekly subcutaneous injection, has been approved as 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).
"Today's FDA approval of KYNAMRO is great news for patients with HoFH
who are in need of additional treatment options for this rare, and often
under-diagnosed disease," said Genzyme President and CEO, David
Meeker, M.D. "As the leader in treatments for rare diseases, we are
pleased to bring our expertise to HoFH patients living with this serious
condition to better help them manage their disease."
HoFH is a rare inherited condition that makes the body unable to remove
LDL cholesterol, often called the "bad" cholesterol, from the blood,
causing abnormally high levels of circulating LDL cholesterol. In the
United States, HoFH, an orphan indication, occurs in approximately one
in one million individuals. For those with HoFH, heart attacks and death
often occur before age 30.
"People living with Homozygous FH may not appear to be sick, but they
live with the burden of this rare disease every day," said Katherine
Wilemon, President and Founder the FH Foundation "The approval of
KYNAMRO gives the HoFH community hope that HoFH can be effectively
The FDA approval triggers a $25 million milestone payment to Isis from
"KYNAMRO is the first systemic antisense drug to reach the market and
is the culmination of two decades of work to create a new, more
efficient drug technology platform. As evidenced by our robust pipeline,
our antisense drug discovery technology is applicable to many
different diseases, including the treatment of a chronic and rare
disease, like HoFH," said Stanley T. Crooke, M.D., Ph.D., Chairman
of the Board and CEO of Isis. "We look forward to continuing to work
with Genzyme toward a successful commercial launch of KYNAMRO and global
expansion into other markets."
The FDA approval for KYNAMRO is supported by the largest clinical trial
conducted to-date in the HoFH patient population. The randomized,
double-blind, placebo-controlled, multi-center trial enrolled 51
patients age 12 to 53 years, including 7 patients age 12 to 16 years,
who were maintaining a regimen of maximally-tolerated lipid lowering
medications. Treatment with KYNAMRO further reduced LDL-C levels by an
average of 113 mg/dL, or 25%, from a treated baseline of 439 mg/dL, and
further reduced all measured endpoints for atherogenic particles. In
March 2010, these data were published in The Lancet by Professor
Raal, University of the Witwatersrand in South Africa.
Safety data for KYNAMRO are based on pooled results from four Phase 3,
randomized, double-blind, placebo-controlled trials with a total of 390
patients of which 261 patients received weekly subcutaneous injections
of 200 mg of KYNAMRO and 129 patients received placebo for a median
treatment duration of 25 weeks. Eighteen percent of patients on KYNAMRO
and 2% of patients on placebo discontinued treatment due to adverse
reactions. The most common adverse reactions in patients treated with
KYNAMRO that led to treatment discontinuation and occurred at a rate
greater than placebo were: injection site reactions (5.0%), alanine
aminotransferase (ALT) increased (3.4%), flu-like symptoms (2.7%),
aspartate aminotransferase (AST) increased (2.3%), and liver function
test abnormal (1.5%).
KYNAMRO is an antisense drug and is metabolized without affecting the
CYP450 pathways used in commonly prescribed drugs, and thus has
potential for no drug-drug interactions. No clinically relevant
pharmacokinetic interactions were reported between KYNAMRO and warfarin,
or between KYNAMRO and simvastatin or ezetimibe.
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
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
As part of its commitment to HoFH patients, Genzyme has developed
KYNAMRO CornerstoneSM, an HoFH and KYNAMRO support program
for healthcare providers, patients, and their families. KYNAMRO
Cornerstone services include:
Dedicated KYNAMRO Cornerstone Case Managers.
Product & disease education for providers, patients, and families.
In-person injection training, if requested.
Reimbursement support, including out-of-pocket financial support, for
patients who qualify.
Coordination of KYNAMRO shipment and delivery.
KYNAMRO Cornerstone Case Managers are available live Monday-Friday from
9 am to 6 pm Eastern time. For more information about KYNAMRO
Cornerstone, or about these support services call 1-877-KYNAMRO
(877-596-2676). For additional information, please visit www.KYNAMRO.com.
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 =3 x 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.
OTHER WARNINGS AND PRECAUTIONS
Patients are advised to read the KYNAMRO medication guide before
starting treatment with KYNAMRO, and each time they receive a refill.
There may be new information. This information does not take the place
of talking to a doctor about a medical condition or treatment.
KYNAMRO may cause serious side effects, including liver problems. A
doctor should be informed of any liver problems, including liver
problems while taking other medicines, or if a patient has any of these
symptoms of liver problems while taking KYNAMRO: nausea, vomiting,
fever, loss of appetite, being (or feeling) more tired than usual,
yellowing of eyes or skin, dark urine, itching, or stomach pain.
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.
KYNAMRO should be used during pregnancy only if clearly needed. Females
who become pregnant during KYNAMRO therapy should notify their
Safety and effectiveness have not been established in pediatric patients.
KYNAMRO is not recommended in patients with severe renal impairment,
clinically significant proteinuria, or on renal dialysis.
The safety and effectiveness of KYNAMRO as an adjunct to LDL apheresis
have not been established; therefore, the use of KYNAMRO as an adjunct
to LDL apheresis is not recommended.
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
Patients with a known hypersensitivity to any component of this
COMMON SIDE EFFECTS
In clinical trials the most commonly-reported adverse reactions were
injection site reactions occurring in 84% of patients receiving KYNAMRO
versus 33% of placebo treated patients. The most common injection site
reactions were erythema (59%), pain (56%), hematoma (32%), pruritus
(29%), swelling (18%) and discoloration (17%). Injection site reactions
did not occur with every injection but resulted in discontinuation of
therapy in 5% of patients in pooled phase 3 trials.
Flu-like symptoms, defined as any one of the following: influenza-like
illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue and
occurring within 2 days of injection, have been reported more frequently
in patients receiving KYNAMRO (30%) versus placebo (16%) in the pooled
Phase 3 trials. Flu-like symptoms did not occur with all injections but
resulted in discontinuation of therapy in 3% of patients in pooled phase
See full prescribing information for more
details about Warnings & Precautions, complete list of Adverse Reactions
and Boxed Warning.
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.
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: it is believed to
occur in only one out of every one million persons. 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 6,000 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, such as greater than 500 mg/dL without treatment,
or 300 mg/dL after taking cholesterol-lowering medication. 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 Sanofi Company
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 Sanofi company, Genzyme benefits from the reach and resources of
one of the world's largest pharmaceutical companies, with a shared
commitment to improving the lives of patients. Learn more at www.genzyme.com.
Sanofi, a global and diversified healthcare leader, discovers, develops
and distributes therapeutic solutions focused on patients' needs. Sanofi
has core strengths in the field of healthcare with seven growth
platforms: diabetes solutions, human vaccines, innovative drugs,
consumer healthcare, emerging markets, animal health and the new
Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York
About Isis Pharmaceuticals, Inc.
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, including Europe. Isis' patents
provide strong and extensive protection for its drugs and technology.
Additional information about Isis is available at www.isispharm.com.
Isis Pharmaceuticals® is a registered trademark of Isis
Genzyme®, KYNAMRO™ and KYNAMRO CornerstoneSM are
registered trademarks of Genzyme Corporation. All rights reserved.
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
forward-looking information and statements are subject to various risks
and uncertainties, many of which are difficult to predict and generally
beyond the control of Sanofi, that could cause actual results and
developments to differ materially from those expressed in, or implied or
projected by, the forward-looking information and statements. These
risks and uncertainties include among other things, the uncertainties
inherent in research and development, future clinical data and analysis,
including post marketing, decisions by regulatory authorities, such as
the FDA or the EMA (News - Alert), regarding whether and when to approve any drug,
device or biological application that may be filed for any such product
candidates as well as their decisions regarding labelling and other
matters that could affect the availability or commercial potential of
such product candidates, the absence of guarantee that the product
candidates if approved will be commercially successful, the future
approval and commercial success of therapeutic alternatives, the Group's
ability to benefit from external growth opportunities, trends in
exchange rates and prevailing interest rates, the impact of cost
containment policies and subsequent changes thereto, the average number
of shares outstanding as well as those discussed or identified in the
public filings with the SEC (News - Alert) and the AMF made by Sanofi, including those
listed under "Risk Factors" and "Cautionary Statement Regarding
Forward-Looking Statements" in Sanofi's annual report on Form 20-F for
the year ended December 31, 2011. Other than as required by applicable
law, Sanofi does not undertake any obligation to update or revise any
forward-looking information or statements.
Isis Forward Looking Statement
This press release includes forward-looking statements regarding
Isis' collaboration with Genzyme, a Sanofi company, and 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, including the planned commercialization 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, 2011 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.
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