|
Isis Pharmaceuticals, Inc. announced additional results from its ongoing Phase 2 open-label extension study of mipomersen in patients with familial hypercholesterolemia (FH)
CARLSBAD, CA, USA | April 14, 2008 | Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced additional results from its ongoing Phase 2 open-label extension (OLE) study of mipomersen in patients with familial hypercholesterolemia (FH). In FH patients exposed to mipomersen for as long as 16 months, the safety profile of the drug continues to be encouraging. Reductions in LDL-cholesterol were also maintained in patients who had responded to treatment in their initial study and continued on treatment.
In this OLE study, patients with FH who were initially enrolled in one of two Phase 2 efficacy studies of mipomersen were allowed to enter the OLE study. All patients in the study were being treated with maximum-tolerated lipid-lowering therapy before and during the study. Most patients received 200 mg/week of mipomersen in addition to maximum-tolerated lipid-lowering therapy. The median duration of continuous exposure in these patients was 38 weeks. The maximum continuous exposure was 64 weeks.
All patients in the study had the opportunity to self-administer mipomersen. Although the study was not designed to measure efficacy, the activity of mipomersen was clearly demonstrated and appeared to be well maintained with longer-term dosing.
With respect to safety, the drug was well tolerated in longer-term treatment. There were no new types of adverse events observed and rates of adverse events decreased during the OLE study from those in the initial efficacy studies.
The following additional observations were made in these patients:
-- Mild injection site reactions remain the most common side effect observation.
-- Injection site reactions did not worsen with longer-term dosing and were not more prevalent in patients who self-administered mipomersen.
-- The incidence and severity of ALT elevations was less in the OLE study than in the initial studies.
-- The maximal ALT seen in this study was 172 U/L.
-- No patient experienced an elevation of transaminase (ALT) associated with increased bilirubin (Hy's Law). There were no bilirubins greater than the upper limit of normal (ULN) observed in any subject.
-- Several patients who experienced increased ALTs either in the OLE study or in the initial studies continued to receive mipomersen and experienced decline in ALTs. No patient who experienced increased ALTs greater than three times the ULN in their initial trial had increased ALT values when they were retreated with mipomersen in the OLE study.
"This open-label extension study suggests that mipomersen can be administered with a satisfactory safety profile and continued LDL reductions for prolonged periods of time in patients with familial hypercholesterolemia being treated with maximal doses of statins and other lipid lowering agents," said Evan Stein, M.D., Ph.D., Director, Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio.
ABOUT MIPOMERSEN
On January 7, 2008, Isis announced the licensing of mipomersen to Genzyme as the preferred partner to continue development, commercialize and market the drug. Isis will transition development responsibility for mipomersen to Genzyme over the next year. In addition to the up-front payment ($150 million for Isis stock at $30 per share and $175 million mipomersen license fee), Isis also has the opportunity to receive from Genzyme up to $825 million in development and regulatory milestone payments plus up to $750 million in commercial milestone payments. Genzyme and Isis will share mipomersen profits. The profit share begins with a 70/30 Genzyme/Isis split and increases linearly to 50/50 when revenue reaches $2 billion.
Mipomersen is a second-generation antisense drug that reduces the production of apoB-100, a protein critical to the synthesis and transport of "bad" cholesterol. Cholesterol can be carried in the bloodstream in a variety of forms, with high-density lipoprotein, or HDL-cholesterol, being the good form, and low-density lipoproteins, or LDL-cholesterol, and very low-density lipoproteins, or VLDL-cholesterol, being bad forms directly involved in heart disease. Collectively lowering LDL-cholesterol, VLDL-cholesterol, and other bad forms of cholesterol are a key component in the prevention and management of cardiovascular disease.
Currently in Phase 3 development, mipomersen has been shown in Phase 2 trials to reduce cholesterol and other atherogenic lipids more than 40 percent beyond reductions achieved with standard lipid-lowering drugs, enabling more patients to achieve LDL-cholesterol targets. These trials have shown that treatment with mipomersen is well-tolerated, and that mipomersen has an attractive safety profile, and works equally well in the presence and absence of other lipid-lowering therapies including statins. A weekly injectable therapeutic, mipomersen is being developed primarily for patients at high cardiovascular risk who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins.
Mipomersen's initial indication will be for patients with FH. There are approximately 1.5 million people in the United States and Europe with FH, an inherited disorder that causes exceptionally high levels of LDL-cholesterol. After appropriate clinical development, the next indication pursued for mipomersen will be for other patients with high cholesterol at high risk of cardiovascular events.
ABOUT FAMILIAL HYPERCHOLESTEROLEMIA (FH)
FH patients have high blood concentrations of LDL-cholesterol due to a genetic disorder which prevents proper metabolism of LDL-cholesterol. These patients experience a markedly increased risk of premature cardiovascular diseases (CVD) and CVD-related death. FH can be present in two forms: homozygous (hoFH), where the same defective gene is inherited from both parents, or heterozygous (heFH), where the defective gene is inherited from only one parent so that some function is preserved. The homozygous form is a very rare condition estimated to affect approximately one in a million people. Children with hoFH are at high risk for early coronary events and sudden death as young as age one. HeFH is more common, with a prevalence of approximately one in 500, and patients with heFH also experience elevated LDL-cholesterol and are at high risk for early coronary events. For undiagnosed or untreated heFH, the cumulative risk of a coronary heart disease by age 60 years is 60-85 percent among men and 30-50 percent among women, with a mean age of onset of approximately 47 years.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 19 drugs in development. Isis' drug development programs are focused on treating cardiovascular and metabolic diseases. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Ibis Biosciences, Inc., Isis' majority-owned subsidiary, is developing and commercializing the Ibis T5000(TM) Biosensor System, a revolutionary system to identify infectious organisms. Isis is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development and commercialization of microRNA therapeutics. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,500 issued patents worldwide. Additional information about Isis is available at http://www.isispharm.com.
SOURCE: Isis Pharmaceuticals, Inc. |
