New Orphan Drug Kynamro Approved For Inherited Cholesterol Disorder

Editor's Choice
Main Category: Cholesterol
Also Included In: Cardiovascular / Cardiology;  Regulatory Affairs / Drug Approvals
Article Date: 30 Jan 2013 - 1:00 PST


Kynamro (mipomersen sodium) injection has been approved by the FDA to treat people who are genetically predisposed to have high levels of LDL cholesterol - what lay people refer to as "bad cholesterol". Kynamro was approved to be taken together with lipid-lowering drugs and diet for patients with HoFH (homozygous familial hypercholesterolemia).

According to the FDA (Food and Drug Administration), adding Kynamro to cholesterol-lowering medications, helps reduce LDL-C (low-density lipoprotein-cholesterol), total cholesterol, non HDL-C (non-high density lipoprotein-cholesterol), and apolipoprotein B.

HoFH is a very rare inherited condition which affects approximately 1 in every one million Americans. The body cannot remove LDL-C from the blood, resulting in excessively high levels of circulating LDL-C.

People with HoFH commonly have heart attacks and die before reaching thirty years of age.

Kynamro is an orphan drug approval

An orphan drug approval means the medication was developed to treat an illness, disorder or condition which affects no more than 200,000 people in the country. In December 2012, Juxtapid (lomitapide) was approved by the FDA to reduce LDL-C, apolipoprotein B, total cholesterol, and non HDL-C in HoFH patients.

Eric Colman, M.D., deputy director of the Division of Metabolism and Endocrinology Products at the FDA's Center for Drug Evaluation and Research, said:

"Kynamro, an injection given once a week, works with other lipid-lowering medications and diet to impair the creation of the lipid particles that ultimately give rise to LDL-C."

When deciding on whether to approve Kynamro, FDA scientists looked at safety and efficacy data from a clinical trial involving 51 patients with HoFH. LDL-C levels fell, on average, by 25% during the first 26 weeks of therapy which included Kynamro.

Patients taking Kynamro run a serious risk of liver toxicity, because the drug is linked to liver enzyme abnormalities and a build-up of fat in the liver, which could eventually lead to progressive liver disease. The drug's packaging carries a Boxed Warning advising doctors and patients of this risk.

In an online communiqué, the FDA wrote "The FDA approved Kynamro with a Risk Evaluation and Mitigation Strategy (REMS) with elements to assure safe use, including prescriber and pharmacy certification, and documentation of safe-use conditions, which requires a prescription authorization form for each new prescription."

The most commonly reported side effects related to Kynamro usage during the clinical trial included flu-like symptoms, nausea, headache, injection site reactions, and elevations in liver enzymes (serum transaminases).

The FDA says it requires four post-marketing studies for Kynamro:

• A long-term registry of patients with HoFH to determine the long-term safety of Kynamro


• A study to assess for the presence of antibodies to ds-DNA in patients treated with Kynamro


• The development of a sensitive assay that binds double-stranded (ds) DNA


• An enhanced pharmacovigilance program to monitor reports of malignancy, immune-mediated reactions, and hepatic abnormalities in patients treated with Kynamro

Kynamro in manufactured and marketed in the USA by the Genzyme Corporation (a Sanofi company), Cambridge, Massachusetts.

Genzyme President and CEO, David Meeker, M.D., said:

"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. 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."

Katherine Wilemon, who is President and Founder of the FH Foundation explained that patients with HoFH might not look sick, but they live with the burden of this very rare disease every day of their lives. This FDA approval of Kynamro gives HoFH patients hope that their condition may be effectively managed, she added.

According to a Genzyme communiqué "The FDA approval triggers a $25 million milestone payment to Isis Pharmaceuticals Inc. from Genzyme."

Kynamro is an antisense drug. It is metabolized with no effect on the CYP450 pathways that commonly prescribed medications use, meaning it has potential for no drug-drug interactions. There were no "relevant" pharmacokinetic interactions reported between Kynamro and ezetimibe or simvastatin, or Kynamro and warfarin.

Written by Joseph Nordqvist


Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

• Additional
• References
• Citations