Genzyme Corp. and Isis Pharmaceuticals, Inc. have announced a major strategic alliance in which Genzyme will develop and commercialise Mipomersen, Isis' lipid-lowering treatment for high risk cardiovascular patients, that utilises novel antisense technology.
As part of the strategic relationship, Genzyme will also have preferred access to future Isis drugs for CNS and certain rare diseases.
Genzyme will pay Isis $150 million to purchase five million shares of Isis common stock for $30 per share upon Hart-Scott-Rodino clearance. Upon completion of final contracts, Genzyme will pay Isis a $175 million up-front Mipomersen license fee. In addition to this initial $325 million, Isis has the potential to receive significant milestone payments for Mipomersen, which is currently in Phase 3 trials. Once the product is launched, the two companies will share profits.
"This alliance is an excellent strategic fit for Genzyme's business model and culture," said Henri A Termeer, Genzyme's chairman and chief executive officer. "Mipomersen is an innovative approach to addressing a real unmet medical need, and we believe it could prove to be the most effective lipid-lowering agent for high risk patients for whom conventional therapies are not sufficient. This potential blockbuster is a very Genzyme-like product. It provides significant benefit over the standard of care, targets a well-defined and severely ill patient population, and offers meaningful revenue and earnings potential."
"We feel that Genzyme is the perfect partner for Isis and for Mipomersen," said Stanley Crooke, chairman, president and chief executive officer of Isis. "We have been very pleased with the quality and depth of interest in this flagship drug in our cardiovascular pipeline, and as we evaluated the licensing terms from various parties, we felt that Genzyme would value Mipomersen appropriately as a pipeline-transforming product. This commitment to Mipomersen, along with Genzyme's strength in drug development and marketing, made this relationship strategically compelling."
Isis will transition development responsibility for Mipomersen to Genzyme over the next two years. In addition to the up-front payment, 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 50/50 when annual worldwide revenues reach $2 billion or more. The profit share begins with a 70/30 Genzyme / Isis split and reaches 50 / 50 on a sliding scale as annual revenues ramp up to $2 billion.
"Genzyme is reconfirming its 2008 and five-year earnings guidance, and we will manage the financial impact of this agreement within our previously stated goal of 20 percent compound annual growth in non-GAAP earnings per share through 2011," noted Mr Termeer.
"We believe the profit sharing transaction we have structured with Genzyme is uniquely beneficial to Isis," added Dr Crooke. "It allows us to benefit in the short term and over time through upfront licensing fees and milestones, while retaining substantial economic participation in the commercialisation of the drug. We look forward to working with Genzyme on Mipomersen as well as potentially on drugs for CNS and certain rare diseases."
Closure of the transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act.
Mipomersen, formerly ISIS 301012, is a lipid-lowering drug targeting apolipoprotein B-100. Currently in phase 3 development, Mipomersen has been shown in phase 2 trials to reduce cholesterol and other atherogenic lipids more than 40 per cent beyond reductions achieved with current standard lipid-lowering drugs, enabling more patients to achieve lipid targets.
These trials have shown that the treatment is well-tolerated, has a strong 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 significant cardiovascular risk who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins. The drug has strong, broad patent protection.
Mipomersen's initial indication will be for patients with familial hypercholesterolemia (FH), with an anticipated filing in 2009. 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.
Familial hypercholesterolemia 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 (CHD) by age 60 years is 60-85 per cent among men and 30-50 per cent among women, with a mean age of onset of approximately 47 years.