The FDA has approved Isis' (ISIS) Drug Kynamro (mipomersen sodium) for Homozygous Familial Hypercholesterolemia (HoFH). Genzyme, a Sanofi (NYSE:SNY) company, and Isis Pharmaceuticals announced the news on Wednesday January 30, 2013. The FDA approved Kynamro's 200 mg weekly subcutaneous injection 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).
The market is small? We know that. Yet we did not miss the fact that January 30, 2013, the day Kynamro's was granted approval, will be recorded in the textbooks of pharmaceutical sciences as the day the first systemically administered antisense therapeutic has been approved by the FDA. This approval is insinuation to a large market, very large as a matter of fact, considering the nature of the therapeutic molecules and the nature of the targets. The approval has officially confirmed the feasibility of creating therapeutic molecules out of Isis' chemically transformed antisense molecules. We also did not miss the fact that the successful development of an antisense molecule will really highlight the firm's pipeline that is full of products - all represent genetic disease that are intractable and life-threatening with unmet treatment needs.
Isis' success was anything but easy. The firm and its scientists had to struggle for around two decades to overcome the multitude of hurdles the antisense technology is known to face. The problems were, indeed, grave. They sounded unsolvable, which led chemists and molecular biologists to classify antisense among the most ambitious, yet, the most difficult to translate into safe and effective therapeutics. That is the main reason analysts believed and some would continue to propagate that the time, effort and money biotech firms have been spending on developing antisense drugs will be washed-out. The same scientists, however, recognized the tremendous value antisense therapeutics would gather if successfully produced.
The FDA approval of Isis' systemically used antisense drug confirmed that the time, effort and money it spent did not go in vain. The impossible was made possible and the firm was capable of bringing to patients an entirely new class of drugs capable of overcoming the limitations of conventional treatments. HoFH patients will soon have in hand a therapeutic called Kynamro, the first drug that works at the root-cause of their inherited disease. HoFH is a rare inherited condition that makes the body unable to dispose of the bad LDL cholesterol, causing abnormally high levels of circulating LDL cholesterol. In the United States, HoFH occurs in approximately one in one million individuals who are threatened with cardiovascular complications and death at an early age - as early as 30 years old.
Of course negative analysts will discourage buying ISIS with the pretext that the HoFH market is too small. For investors to know better, they must understand that the success of therapeutic antisense molecules is extremely helpful in creating more antisense successful molecules. All the products have the same molecules, but directed against various targets. The money, investors realize, resides in the firm's rich promising pipeline whose value should be revised in the light of Kynamro's approval, the difference is expected to be soon reflected on the stock price.
The FDA approval for Kynamro is supported by the largest clinical trial conducted to-date in the HoFH. The drug is metabolized without affecting the CYP450 pathways used in commonly prescribed drugs, and thus has potential for no drug-drug interactions. As a matter of fact, no clinically relevant pharmacokinetic interactions were reported between Kynamro and warfarin, or Kynamro and simvastatin or ezetimibe.
To read the complete text with the detailed clinical trials and safety precautions Click here.
What has Isis accomplished during the two decades in the antisense arena?
The firm must have come to an understanding that what makes a task difficult is the lack of knowledge of detailed knowledge about all the aspects of the task in hand. Isis spent the time, effort and money on understanding the molecular mechanisms related to antisense drugs. It exploited many of at least 12 antisense mechanisms at work once an antisense drug binds to its target RNA. The increased knowledge helped the choice of chemical modifications made to original molecules that have, indeed, enhanced the performance of its antisense therapeutics, overcoming, among others, the problems of rapid degradation and solubility of the antisense molecules and other large and small problems preventing safe and effective use of the antisense molecules as therapeutics.
Isis has cloned and characterized human RNase H and used that information to optimize the design of many of its antisense drugs. The work is still in progress by Isis in order to further advance its understanding of antisense mechanisms, including RNase H, in order to improve the pharmaceutical properties of its drugs.
Last in this article, but not last at Isis' laboratory is that two years ago, the firm identified an antisense drug, ISIS-SMNR, for spinal muscular atrophy (SMA) - a splicing disease and the leading genetic cause of infant mortality. The discovery of ISIS-SMNR resulted from a research collaboration with Cold Spring Harbor. In earlier published research, Isis and Cold Spring Harbor scientists demonstrated the feasibility of using Isis antisense technology to control splicing for the treatment of SMA.
In addition, Isis is contributing to exploiting what the scientific community has recently discovered, which comprises microRNAs and RNA interference (RNAi) involved in the regulation of natural protein production within the cell. The firm has collaborated with Alnylam (NASDAQ:ALNY) in creating a specialized firm, Rugulus, which is making great discoveries and creating new microRNA molecule therapeutics. Regulus is expected to turn public at any time now.
Bottom line, The antisense technology has improved and created effective drugs and is further improving to reach the level where it will control the market of chronic and life-threatening genetic diseases.
In addition to Isis and alnylam, Sarepta (NASDAQ:SRPT), which used to be known by the name AVI Pharmaceuticals, is developing its own proprietary far-reaching antisense molecule therapeutics. A few months ago, the firm unveiled results of its lead product eteplirsen for Duchene muscular dystrophy. The drug demonstrated a successful production of dystrophin, a rod-shaped cytoplasmic protein and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. Dystrophin deficiency has been definitively established as one of the root-causes muscle dystrophy. The stock price multiplied several folds. We love to hear such good news.
Disclosure: Long Isis.
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