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Pending FDA Events
Isis Pharma - Making Sense Of Antisense
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1/4/2012 8:57 AM ET

(RTTNews) - First conceived in 1978, the concept of antisense drugs for treating diseases has come a long way. Antisense drugs work by blocking the production of disease-causing proteins altogether, while traditional drug therapies work by interacting with the disease-causing proteins.

A pioneer in antisense drug development, Isis Pharmaceuticals Inc. (ISIS: News ) is all set to seek approval for systemic antisense lipid-lowering drug Mipomersen that will be marketed under the brand name Kynamro.

Mipomersen, which is a weekly injectable therapeutic, works by decreasing the production of apolipoprotein-B that is responsible for carrying cholesterol to tissues. The drug candidate was licensed to Genzyme in 2008, which is now a unit of French pharmaceutical giant Sanofi (SNY).

In phase III studies, Mipomersen has been evaluated in both homozygous and heterozygous familial hypercholesterolemia patients. Familial hypercholesterolemia is a genetic disease that results in elevated low-density lipoprotein, or LDL-C, often referred to as bad cholesterol levels, and is associated with high risk of premature heart disease and heart disease-related death.

Familial hypercholesterolemia includes homozygous familial hypercholesterolemia patients - those who have inherited the disease from both parents and heterozygous familial hypercholesterolemia patients - those who have inherited the disease from only one parent.

In a late-stage trial involving homozygous familial hypercholesterolemia patients, Mipomersen met the study's primary endpoint with 25 percent LDL-C reduction, and in heterozygous familial hypercholesterolemia patients, the drug candidate met the trial's primary endpoint with a 28 percent LDL-C reduction.

Last July, a marketing authorization application was submitted by Genzyme to the European Medicines Agency seeking approval for Mipomersen 200 mg weekly dose for the treatment of homozygous and severe heterozygous familial hypercholesterolemia.

A New Drug Application seeking approval of Kynamro for the treatment of homozygous familial hypercholesterolemia is expected to be submitted to the FDA in the first quarter of 2012. The regulatory agency has sought an additional 12 month clinical data before an approval is sought for Kynamro for severe heterozygous familial hypercholesterolemia in the U.S.

It is estimated that there are roughly 40,000 patients in Europe and the U.S. with homozygous familial hypercholesterolemia and severe heterozygous familial hypercholesterolemia.

Familial hypercholesterolemia is treated with statins like Mevacor, Pravachol, Zocor, Lescol, Lipitor, Crestor and cholesterol-lowering medicines like bile acid-sequestering resins, Ezetimibe, Fibrates and Nicotinic acid. However, the current drug therapies are not sufficient to lower LDL cholesterol levels to a safe range. Isis expects Mipomersen to be a breakthrough, potential blockbuster.



"Isis expects Mipomersen to be a breakthrough, potential blockbuster. "

ACES alerted us to the inportance of Mipomersen in Nov/2011 re Validation..for us in ANP..$$$$$