Genzyme, a Sanofi company, and Isis Pharmaceuticals Inc. announced that new two-year data from a phase 3 long-term extension study of Kynamro (mipomersen sodium) were presented at the XVI International Symposium on Atherosclerosis in Sydney, Australia. In the study, patients treated with Kynamro for two years maintained robust reductions in LDL-C and all other Apo B containing atherogenic lipoproteins measured with a safety profile consistent with the phase 3 studies of Kynamro.
Data presented included 141 patients who enrolled in the study after having completed one of the three phase 3 studies: homozygous FH, severe hypercholesterolemia, or the heterozygous FH. These studies were six months long and required patients to be on stable maximally tolerated lipid-lowering therapy throughout the study. To date, 63 patients remain on or have completed treatment with 40 patients consenting to participate for another two years of treatment – a total of four years of treatment.
In this study, sustained reductions in LDL-C with a mean reduction of 28% in LDL-C at six months and at two years were observed in patients treated with Kynamro. Changes in liver fat were observed in some patients where the overall median change stabilized and then declined with continued treatment. The median change from baseline in% liver fat increased from 5% at 26 weeks, to 13% at 52 weeks, and returned to 5% at 104 weeks. Results represent those patients in the extension study at each assessment period: 60 patients at 26 weeks, 31 patients at 52 weeks, and 39 patients at 104 weeks. The median change reflects both patients who continued at full dose as well as those with dose adjustments and dose interruptions. Upon treatment discontinuation, changes in liver fat returned towards normal.
“These data show that robust LDL-C reductions are seen in patients treated for 2 years and more. Liver fat may increase in some patients but in this long term study the median fat fraction is seen to stabilize and decline with time as measured by MRI,” said study investigator Raul D. Santos, M.D., Ph.D., Director of the Lipid Clinic of the Heart institute, Instituto do Coração, Hospital das Clínicas, São Paulo, Brazil. “These results are encouraging and support the potential for effective and safe long-term use in patients with the most aggressive forms of FH.”
Genzyme and Isis have completed the four phase 3 studies that are included in the European submission and will be included in the U.S. submission. In these studies, the most commonly observed adverse events were injection site reactions and flu-like symptoms. The long-term data demonstrate a safety and efficacy profile consistent with phase 3 findings.
“These positive and clinically meaningful results represent a significant addition to the Kynamro clinical development program,” said Vice President and General Manager of Genzyme’s Cardiovascular Business, Paula Soteropoulos. “We look forward to continuing to work with regulatory authorities to bring this treatment to market for such a severe and life-threatening disease.”
Kynamro is the registered trade name submitted to health authorities for investigational agent mipomersen. Genzyme submitted for EU marketing approval of Kynamro for the treatment of patients with homozygous FH (HoFH) and severe heterozygous FH (Severe HeFH) in July 2011. Genzyme also expects to submit an NDA for U.S. approval for the HoFH indication by the end of March 2012.
Date: March 29, 2012
Filed Under: Drug Discovery