Positive results from the phase 3 ODYSSEY ESCAPE trial evaluating Alirocumab ( Praluent ) injection in patients with an inherited form of high cholesterol known as heterozygous familial hypercholesterolemia ( HeFH ), whose cholesterol levels required chronic, weekly or bi-weekly apheresis therapy, were announced.
The trial met its primary endpoint, demonstrating that patients who added Alirocumab, a PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitor, to their existing treatment regimen significantly reduced the frequency of their apheresis therapy by 75%, compared to placebo ( p less than 0.0001 ).
Sixty-three percent of patients treated with Alirocumab no longer required apheresis, compared to zero percent of placebo patients.
Apheresis is a procedure where LDL cholesterol is removed from the blood, in a process similar to kidney dialysis, and it is invasive and burdensome to patients, given that it can take more than three hours. Treatment may also be inconvenient and cost up to $100,000 for each patient per year in the U.S. or up to €60,000 in Germany, where there are 200 centers and LDL apheresis is more frequently used. In the U.S. there are only approximately 60 apheresis centers and many patients must travel significant distances for the procedure.
Despite statins, a subset of patients with heterozygous familial hypercholesterolemia are unable to sufficiently reduce their LDL cholesterol, and require regular apheresis treatment.
The results have demonstrated that treatment with Alirocumab may help these patients decrease the frequency or even eliminate the need for apheresis.
The most common adverse events in the trial were fatigue ( 15% Alirocumab; 10% placebo ), nasopharyngitis ( 10% vs 10% ), diarrhea ( 10% vs 0% ), myalgia ( 10% vs 5% ), upper respiratory infection ( 7% vs 19% ), headache ( 7% vs 5% ), arthralgia ( 7% vs 10% ), and back pain ( 5% vs 10% ).
The completed phase 3 placebo-controlled ODYSSEY ESCAPE trial involved 62 patients from 14 treatment centers in the U.S. and Germany. These patients were receiving regular baseline apheresis therapy at fixed intervals of every week or every 2 weeks prior to randomization.
Patients were randomized to receive Alirocumab 150 mg ( n=41 ) subcutaneously every 2 weeks or placebo ( n=21 ), in addition to their existing treatment regimen.
The double-blind treatment period comprised two intervals: for the first 6 weeks, patients remained on their established apheresis schedule at baseline, and for the following 12 weeks, apheresis frequency was adjusted based on the patient's LDL cholesterol response to treatment.
ODYSSEY ESCAPE is part of the overarching phase 3 ODYSSEY program, which includes more than 25,000 patients. ( Xagena )
Source: Sanofi, 2016