New HoFH drug, KYNAMRO, approved by the FDA

On January 29th, 2013, Genzyme (a Sanofi company), and Isis Pharmaceuticals Inc. announced that after two years of patient clinical trials the US Food and Drug Administration has approved Kynamro ™ (generic name: mipomersen sodium) for the treatment of Homozygous Familial Hypercholesterolemia, the most severe form of FH. Kynamro is an injection to be administered once a week as an addition to other therapeutic methods such as cholesterol-lowing medications and diet regime. The drug enables the reduction of low-density lipoprotein-cholesterol (LDL or “bad” cholesterol), total cholesterol, non-high density lipoprotein cholesterol (non HDL-C) and apolipoprotein B.

In regards to the study results one of the participating researchers, Raul D. Santos, M.D., Ph.D., (Director of the Lipid Clinic of the Heart institute, Instituto do Coração, Hospital das Clínicas, São Paulo, Brazil ) notes, “These data show that robust LDL-C reductions are seen in patients treated for 2 years and more. Liver fat may increase in some patients but in this long term study the median fat fraction is seen to stabilize and decline with time as measured by MRI. These results are encouraging and support the potential for effective and safe long-term use in patients with the most aggressive forms of FH.

Homozygous FH (HoFH) is a very rare and aggressive form of FH, which affects roughly 1 in a million people worldwide. This genetic condition may occur if a child inherits the FH gene from both parents who also have some form of FH, and results in abnormally high levels of LDL-cholesterol from a young age and premature heart disease (individuals can have a heart attack as early as their teens if left untreated).

“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 of the Family Heart Foundation “The approval of KYNAMRO gives the HoFH community hope that HoFH can be effectively managed.”

The results from a clinical trial with 51 patients suffering from HoFH showed that levels of LDL-C (“bad” cholesterol) dropped by ~25% within the first 26 weeks of treatment with Kynamro. The most commonly experienced adverse effects in patients were flu-like symptoms, nausea, injection reactions and elevations in liver enzymes. The degree of long-term safety of the drug is described in its Boxed Warning (below), which alerts of potential liver damage. To assure safe use of Kynamro, the FDA has approved it with a Risk Evaluation and Mitigation Strategy (REMS), meaning that it requires prescription and pharmacy certification.

Important Safety information and Boxed Warning


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.


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 healthcare provider.

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 transaminases.
  • Patients with a known hypersensitivity to any component of this product.


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.

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