The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency today recommended that mipomersen (Kynamro, Isis and Genzyme) not be approved for use in Europe. The novel antisense oligonucleotide works by inhibiting the synthesis of apo-B and is under development in the United States and Europe for the treatment of familial hypercholesterolemia.
CHMP agreed that mipomersen effectively lowered LDL cholesterol in people with homozygous and severe heterozygous familial hypercholesterolemia. The negative recommendation was based on the committee’s concerns about the safety of mipomersen. Here is the CHMP discussion of the safety issue:
However, the CHMP was concerned about the medicine’s safety. The Committee noted that a high proportion of patients stopped taking the medicine within two years, even in the restricted group of patients with homozygous familial hypercholesterolemia, mainly due to side effects such as flu-like symptoms, injections site reactions and liver toxicity. This was considered important because Kynamro is intended for long-term treatment in order to maintain the cholesterol-lowering effect. The CHMP was also concerned by liver test results in patients taking Kynamro showing a build-up of fat in the liver and increased enzyme levels, and was not convinced that the company had proposed sufficient measures to prevent the risk of irreversible liver damage. Moreover, the Committee was concerned that a greater proportion of patients taking Kynamro experienced serious cardiovascular events (problems with the heart and blood vessels) than patients taking placebo. This prevented the CHMP from concluding that Kynamro’s intended cardiovascular benefit, in terms of reducing cholesterol levels, outweighed its cardiovascular risk.
In October the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee gave a weak endorsement to mipomersen, voting 9-6 in favor of an approval recommendation. Comments during the panel meeting, however, clearly indicated that committee members were concerned about both the efficacy and safety of the drug.
Another new drug under development for lowering cholesterol in FH patients is lomitapide (Aegerion). The same FDA panel in October gave lomitapide a slightly stronger approval recommendation.
The CEO of Genzyme expressed disappointment with CHMP’s recommendation. “Patients with HoFH carry extreme, ongoing cardiovascular risk with significantly elevated LDL-C levels despite use of currently available therapies. This is a rare disease patient population, with a life-threatening condition, in need of new therapies. We will work closely with the CHMP during the re-examination process to address the Committee’s concerns, with the goal of making this important medication available to HoFH patients in Europe.”
Here is the Genzyme press release:
|Genzyme and Isis Provide Update on CHMP Opinion on KYNAMRO™ (mipomersen)|
|CAMBRIDGE, Mass. & CARLSBAD, Calif.–(BUSINESS WIRE)–Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), and Isis Pharmaceuticals Inc. (NASDAQ: ISIS), today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a negative opinion for its marketing authorization application (MAA) for KYNAMROTM (mipomersen) for the treatment of patients with Homozygous Familial Hypercholesterolaemia (HoFH). Genzyme plans to request a re-examination of the CHMP Opinion.
“We are disappointed by the Committee’s recommendation. Patients with HoFH carry extreme, ongoing cardiovascular risk with significantly elevated LDL-C levels despite use of currently available therapies,” said David Meeker, President and CEO, Genzyme. “This is a rare disease patient population, with a life-threatening condition, in need of new therapies. We will work closely with the CHMP during the re-examination process to address the Committee’s concerns, with the goal of making this important medication available to HoFH patients in Europe.”
“We believe that we have generated significant evidence in support of KYNAMRO,” said B. Lynne Parshall, Chief Operating Officer and CFO of Isis.“Patients are in need of new options and we will continue to work with our colleagues at Genzyme toward the marketing approval of KYNAMRO.”
An application for KYNAMRO is currently under review by the U.S. Food and Drug Administration (FDA). In October 2012, KYNAMRO received a positive vote by an FDA advisory panel that Genzyme had provided sufficient efficacy and safety data to support the marketing of KYNAMRO for the treatment of patients with Homozygous Familial Hypercholesterolaemia (HoFH).
About KYNAMRO (mipomersen)
KYNAMRO is a first-in-class apo-B synthesis inhibitor currently under regulatory review for patients with homozygous familial hypercholesterolaemia (HoFH) to further reduce LDL cholesterol (LDL-C) in patients already maintaining a stable regimen of maximally-tolerated lipid-lowering therapies, and who require additional significant lipid-lowering therapy. It is intended to reduce LDL-C by preventing the formation of atherogenic lipoproteins, the particles that carry cholesterol through the bloodstream. KYNAMRO acts by blocking the production of apolipoprotein B (apo B), the protein that provides the structural core for these atherogenic particles, including LDL and lipoprotein-a (Lp(a)).
About Familial Hypercholesterolaemia (FH)
FH is a genetic disease that results in elevated LDL-C levels and family patterns of increased risk of premature heart disease and heart disease-related death. FH patients have inherited abnormalities in liver cells that are responsible for clearing LDL particles from the blood. FH is autosomal dominant, which means that all first-degree relatives of FH patients have a 50 percent chance of having the disease as well, making early detection through family screening critically important.
The most severe FH patients have LDL-C levels that are two to four times higher than recommended levels, even when taking multiple cholesterol-lowering medications. These people, who are characterized as having severe FH, include: those who have inherited the disease from both parents (HoFH) and those who have inherited it from only one parent, and have a particularly severe form of the disease (Severe HeFH) defined as those people who are maximally treated and still have LDL-C greater than 200 mg/dL (5.1 mmol) with coronary heart disease or greater than 300 mg/dL (7.1 mmol) without coronary heart disease. People with HoFH may have aggressive heart disease beginning in childhood, and even with today’s therapies remain at significant risk of cardiovascular events. Learn more at www.FHJourneys.com.
About Genzyme, a Sanofi Company
Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases for over 30 years. We accomplish our goals through world-class research and with the compassion and commitment of our employees. With a focus on rare diseases and multiple sclerosis, we are dedicated to making a positive impact on the lives of the patients and families we serve. That goal guides and inspires us every day. Genzyme’s portfolio of transformative therapies, which are marketed in countries around the world, represents groundbreaking and life-saving advances in medicine. As a Sanofi company, Genzyme benefits from the reach and resources of one of the world’s largest pharmaceutical companies, with a shared commitment to improving the lives of patients. Learn more atwww.genzyme.com.
Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
About Isis Pharmaceuticals, Inc.
Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners. Isis’ broad pipeline consists of 25 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic and severe and rare/neurodegenerative diseases, and cancer. Isis’ partner, Genzyme, plans to commercialize Isis’ lead product, KYNAMRO, following regulatory approval. Isis’ patents provide strong and extensive protection for its drugs and technology. Additional information about Isis is available at www.isispharm.com.
Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.
Genzyme® is the registered trademark of Genzyme Corporation. All rights reserved.
KYNAMRO™ is the registered trademark of Genzyme Corporation submitted to health authorities for investigational agent mipomersen. All rights reserved.
Sanofi Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group’s ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2011. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.
Isis Forward Looking Statement
This press release includes forward-looking statements regarding Isis’ collaboration with Genzyme, a Sanofi company, and the development, activity, therapeutic benefit and safety of KYNAMRO™ in treating patients with high cholesterol. Any statement describing Isis’ goals, expectations, financial or other projections, intentions or beliefs, including the planned commercialization of KYNAMRO, 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 drugs. 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, 2011 and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.