CAMBRIDGE, Mass. and CARLSBAD, Calif., Aug. 6 Genzyme Corp. (Nasdaq: GENZ) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS)today announced that they have begun a phase 3 study of mipomersen in patientswith heterozygous familial hypercholesterolemia (heFH), a genetic disorderthat causes exceptionally high levels of LDL cholesterol. It is the first offour new trials the companies plan to initiate by the end of this year, andthe second late-stage study of mipomersen, a novel lipid-lowering drug thatutilizes antisense technology.
The companies also announced that the United States Patent and TrademarkOffice granted the patent entitled "Antisense Modulation of Apolipoprotein B(apoB) Expression," U.S. Patent No. 7,407,943. The patent broadly covers theuse of antisense compounds targeting the apoB messenger RNA except a ribozyme.
"We are making excellent progress in implementing our comprehensivedevelopment plan for mipomersen," stated John P. Butler, president ofGenzyme's renal, endocrine and cardiovascular business units. "The start ofthe heFH study puts us on track to meet our goal of beginning four newmipomersen studies this year. In addition, the recent patent issuanceincreases the overall value of mipomersen, which we believe has enormouspotential to help patients."
The new trial will evaluate the safety and efficacy of mipomersen inpatients who have heFH and coronary artery disease. It is a randomized,double-blind, placebo-controlled study taking place at approximately 30 sitesin the U.S. and Canada, with an anticipated total enrollment of around 100patients. Patients on a stable dose of other lipid-lowering agents are beingrandomized 2:1 to receive a 200 mg dose of mipomersen or placebo weekly for 26weeks. The primary endpoint will be percent reduction in LDL cholesterol, anddata are expected to be available in 2010. The trial will add to the body ofclinical data on mipomersen and the overall product profile.
"This is an exciting moment for mipomersen, combining the initiation ofthe phase 3 trial in heFH with a very broad patent allowance that expands thepatent coverage for the apoB franchise," said Stanley Crooke, chairman andchief executive officer of Isis. "This comprehensive patent covers methods ofinhibiting apoB by targeting anywhere on the messenger RNA including the siteto which mipomersen binds, and all therapeutic uses that might result fromlowering apoB."
Mipomersen Development Plan
The initial indication sought for mipomersen will be for patients withhomozygous FH, and enrollment in a phase 3 trial in this patient population isexpected to be completed by the end of this year. Data are expected to beavailable in mid-2009 and a U.S. filing for this indication is anticipatedduring the second half of 2010.
Genzyme and Isis plan to begin three additional trials evaluatingmipomersen's safety and efficacy in reducing LDL cholesterol in high-riskpatients during the second half of 2008. These trials will include: one forapheresis-eligible patients, and two for high-risk, high cholesterol patients.All three have anticipated trial designs that include a 2:1 randomizationratio of a 200 mg dose of mipomersen or placebo weekly for 26 weeks.
These trials will continue to build the body of clinical evidence aroundmipomersen's value in managing very high risk patients. Data from the trialswill also inform the design of the morbidity and mortality outcome study forpotential expansion of mipomersen's label to include a broader group ofat-risk, high cholesterol patients on maximally tolerated, currently availabletherapies.
Following the finalization in June of the mipomersen license andcollaboration agreement between Genzyme and Isis, the mipomersen IND and allregulatory authority has been transferred to Genzyme. Now that thistransition has taken place, the companies are looking forward to