Genzyme and Isis Announce FDA Approval of KYNAMRO (mipomersen sodium) Injection for the Treatment of Homozygous Familial Hypercholesterolemia Paris, France and Carlsbad, California

Genzyme and Isis Announce FDA Approval of KYNAMRO

(mipomersen sodium) Injection for the Treatment of Homozygous Familial Hypercholesterolemia

Paris, France and Carlsbad, California, January 29, 2013 Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary

Genzyme, 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 do 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 Genzyme.

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 a weekly subcutaneous injection 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 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 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:

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:

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.

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 healthcare provider.

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:

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 3 trials.

See full prescribing information for more details about

Warnings & Precautions, complete list of Adverse Reactions and Boxed Warning.

About KYNAMRO (mipomersen sodium)

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 (NYSE: SNY).

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