The trial currently screening patients will evaluate the safety and efficacy of mipomersen in patients with severe hypercholesterolemia who are on a maximally tolerated lipid-lowering regimen (previously referred to as apheresis-eligible patients). This phase 3 study includes patients who are not on LDL cholesterol apheresis but who have such severely elevated LDL-C levels that they are eligible for the procedure, and will enroll up to 75 patients.
In addition, the companies recently initiated a phase 3 trial in hypercholesterolemic patients on maximally tolerated dosages of statins who are at high risk for coronary heart disease. This study will enroll up to 180 patients. The companies have also begun a new phase 2 study in high-risk, high-cholesterol patients who are intolerant to statins, which will enroll up to 30 patients.
All three new trials are double-blind, placebo-controlled studies in which patients will be randomized 2:1 to receive a 200 mg dose of mipomersen or placebo weekly for 26 weeks, with percent change in LDL-C as the primary endpoint.
The companies in August began a phase 3 trial of mipomersen in patients with heterozygous familial hypercholesterolemia (heFH), a genetic disorder that causes severely elevated LDL-C levels.
"With the start of these studies, we will have begun four new mipomersen trials since we formed our collaboration with Isis," stated John P. Butler, president of Genzyme's renal, endocrine, and cardiovascular business units. "We are very excited about the progress we are making on our development plan to learn more about mipomersen's use in lipid management for patients with the highest unmet medical need."
"Together with our partners at Genzyme we have made great strides in moving mipomersen forward, creating the momentum to take us into 2009 and beyond. Data from these new studies should greatly enhance our understanding of the safety and efficacy of mipomersen as we move it toward an NDA," said Stanley T. Crooke, Chairman and CEO of Isis Pharmaceuticals. "We continue to believe that the Genzyme/Isis team is ideal to bring this exciting new drug to patients in need."
The initial indication sought for mipomersen will be for patients with homozygous FH, and enrollment in a phase 3 trial in this patient population is complete. Top-line data are expected to be available in mid-2009, and the submission of a U.S. marketing application for this indication is anticipated during the second half of 2010. Genzyme continues to engage in discussions with regulatory authorities outside the U.S. regarding the development path for mipomersen.
Data from the four new studies of mipomersen will continue to build the body of clinical evidence around the treatmentâs value in managing high-risk, high-cholesterol patients. Data are expected to be available before the companies begin an outcome study of mipomersen, and will help inform that trialâs design. The study, anticipated to begin in mid-2010, is intended to support potential expansion of mipomersen's label to include a broader group of at-risk, high cholesterol patients.
Mipomersen is a first-in-class apo-B synthesis inhibitor currently in phase 3 development. It is intended to reduce LDL-C by preventing the formation of atherogenic lipoproteins. In phase 2 studies, mipomersen, a weekly injectable therapeutic, was observed to reduce LDL-C beyond reductions achieved with standard lipid-lowering drugs, enabling more patients to achieve LDL-C targets. It was also observed to reduce triglycerides, lipoprotein(a), and serum apo-B, all generally accepted risk factors for cardiovascular disease. In 2008 Genzyme and Isis completed a licensing agreement that provides Genzyme with exclusive worldwide rights to mipomersen, which was discovered and initially developed by Isis.
One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 10,000 employees in locations spanning the globe and 2007 revenues of $3.8 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.
With many established products and services helping patients in nearly 90 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.
Genzyme's press releases and other company information are available at www.genzyme.com.
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. Isis is a joint owner of Regulus Therapeutics Inc., a joint venture focused on the discovery, development and commercialization of microRNA therapeutics. Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing. As an innovator in RNA-based drug discovery and development, Isis is the owner or exclusive licensee of over 1,600 issued patents worldwide. Additional information about Isis is available at www.isispharm.com.