Mipomersen Phase 3 Study in HoFH Patients Featured in The Lancet
CAMBRIDGE, Mass. & CARLSBAD, Calif.--(BUSINESS WIRE)--Mar 15, 2010 - Genzyme Corp. (NASDAQ: GENZ) and Isis Pharmaceuticals Inc. (NASDAQ: ISIS) today announced that data from a phase 3 study of mipomersen in patients with homozygous familial hypercholesterolemia (hoFH) were published in The Lancet. This study met its primary endpoint, resulting in an average LDL-C reduction of greater than 100 mg/dL in this very high-risk patient population.
“Currently available treatments do not provide adequate lipid lowering for hoFH patients, leaving them at extraordinarily high risk for cardiovascular events,” said Professor Frederick J. Raal, M.D., Ph.D., Director of the Carbohydrate and Lipid Metabolism Research Unit at the University of the Witwatersrand in South Africa, and the study's primary investigator. “Mipomersen has the potential to set a new standard of care for this difficult-to-treat disease.”
The trial, one of the largest conducted to date in this rare patient population, was designed to test the efficacy and safety of adding mipomersen to substantial lipid-lowering therapy. Patients treated with mipomersen had a 25 percent LDL-C reduction in an intent-to-treat analysis. In addition to meeting its primary endpoint, the trial also met each of its secondary and tertiary endpoints, which included statistically significant reductions in apolipoprotein-B, total cholesterol, non-HDL cholesterol, Lp(a), VLDL-C and triglycerides.
Familial hypercholesterolemia (FH) is a genetic disorder that results in elevated LDL cholesterol levels. FH patients experience a markedly increased risk of premature cardiovascular disease (CVD) and CVD-related death. There are two forms of FH: homozygous, estimated to affect approximately one in a million people worldwide; and heterozygous, a more common form of the disorder with a prevalence of approximately one in 500. In patients with hoFH, the first cardiovascular events can occur in childhood or adolescence. Without lipid-lowering therapy, hoFH patients rarely live beyond age 30.
Although all but one of the 51 patients in the phase 3 study were being treated with lipid-lowering therapy, their average LDL-C at baseline was greater than 400 mg/dL. The LDL-C reductions observed in the study were in addition to those achieved with the patients' existing therapeutic regimens.
“These results are exciting news for hoFH patients, who are in great need of new treatment options,” said Mary McGowan, M.D., of the Concord Hospital Cholesterol Treatment Center, Concord, NH, and a board member of the National Lipid Association. “Mipomersen could make a major difference for these patients.”
The trial was a randomized, double-blind, placebo-controlled study that enrolled hoFH patients aged 12 and older; seven patients were aged 12 to 17. Patients were randomized 2:1 to receive a 200 mg dose of mipomersen or placebo via weekly subcutaneous injections for 26 weeks. The study was conducted at 10 sites in seven countries in North America, Europe, Asia, South America and Africa.
Consistent with previous studies evaluating mipomersen, among the most commonly observed adverse events were injection site reactions, flu-like symptoms and elevations in liver transaminases. Of the 34 patients treated with mipomersen, 28 completed the study. One patient discontinued due to elevations in liver transaminases.
Results of this study were presented by Professor Raal at the annual American Heart Association meeting in November 2009. Study investigator Dr. William Cromwell, Chief of the Division of Atherosclerosis and Lipoprotein Disorders at the Presbyterian Cardiovascular Institute in Charlotte, North Carolina, also presented at AHA on the effects of mipomersen on Lp(a) within the trial.
Mipomersen is a first-in-class apo-B synthesis inhibitor currently in late-stage development. It is intended to reduce LDL-C by preventing the formation of atherogenic lipids. It acts by decreasing the production of apo-B, which provides the structural core for all atherogenic lipids, including LDL-C, which carry cholesterol through the bloodstream.
Genzyme's initial U.S. and E.U. regulatory filings for mipomersen will seek marketing approval for the treatment of patients with hoFH. In the first half of 2011, Genzyme expects to file for U.S. and E.U. approval of the treatment and to have made progress toward filing in other major international markets.
These two filings may also include patients with severe hypercholesterolemia. A phase 3 study of mipomersen in this patient population is fully enrolled and data are expected in mid-2010. The companies have also completed enrollment in a phase 3 trial involving patients at high risk for coronary heart disease, and data are anticipated in mid-2010.
Genzyme and Isis last month reported that a phase 3 study of mipomersen in heterozygous familial hypercholesterolemia (heFH) met its primary endpoint with a 28 percent reduction in LDL-cholesterol after 26 weeks of treatment, compared with an increase of 5 percent for placebo. The trial also met each of its secondary endpoints. Data will be submitted for presentation at a future medical meeting.
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 12,000 employees in locations spanning the globe and 2009 revenues of $4.5 billion.
With many established products and services helping patients in approximately 100 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 and by calling Genzyme's investor information line at 1-800-905-4369 within the United States or 1-678-999-4572 outside the United States.
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 22 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer. Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases. Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company 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.
Genzyme Safe Harbor Statement
This press release contains forward-looking statements regarding Genzyme's future business plans and strategies including, without limitation, statements about the expected timing of the mipomersen development plan, clinical trial results and regulatory filings; and the potential uses and benefits of mipomersen. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those forecasted. These risks and uncertainties include, among others: the actual timing of the completion of the analysis of the clinical study results; Genzyme's ability to accurately understand and predict the outcome and impact of its clinical studies related to mipomersen; Genzyme's ability to continue to support its clinical and other development efforts related to mipomersen; the actual efficacy and safety of mipomersen; the outcome of discussions with regulatory authorities regarding clinical studies of mipomersen; and the risks and uncertainties described in Genzyme's SEC reports filed under the Securities Exchange Act of 1934, including the factors discussed under the caption "Risk Factors" in Genzyme's Annual Report on Form 10-K for the year ended December 31, 2009. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release and Genzyme undertakes no obligation to update or revise the statements.
Genzyme® is a registered trademark of Genzyme Corporation. All rights reserved.
Isis Safe Harbor Statement
This press release includes forward-looking statements regarding Isis' collaboration with Genzyme Corporation, its financial and business development activities, and the development, activity, therapeutic potential and safety of mipomersen in treating patients with high cholesterol. Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such products. Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2009, which is on file with the SEC. Copies of these and other documents are available from the Company.
Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals, Inc. Regulus Therapeutics is a trademark of Regulus Therapeutics Inc.
Erin Emlock, 617-768-6923 (Media)
Patrick Flanigan, 617-768-6563 (Investors)
Amy Blackley, Ph.D., 760-603-2772 (Media)
Kristina Lemonidis, 760-603-2490 (Investors)
Posted: March 2010