Clinical Trials

Date: 2016-08-29

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the ESC Congress 2016 in Rome

Company: Sanofi (France) Regeneron Pharmaceuticals (USA - NY)

Product: Praluent® (alirocumab - SAR236553/REGN727)

Action mechanism:

• monoclonal antibody/RNAi/PCSK9 inhibitor. Alirocumab is a subcutaneously administered, fully-human antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) in clinical development. By inhibiting PCSK9, a determinant of circulating LDL-cholesterol levels in the blood, REGN727 increases the number of free LDL receptors which can bind to circulating LDL and clear it from the bloodstream. REGN727 was created using Regeneron's pioneering VelocImmune® technology and is being developed by Regeneron in collaboration with Sanofi.

Disease: heterozygous familial hypercholesterolemia (HeFH)

Therapeutic area: Cardiovascular diseases - Genetic diseases - Rare diseases

Country: Germany, USA

Trial details:

• This trial is a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effect of alirocumab in comparison with placebo on the frequency of LDL apheresis treatments in patients with HeFH undergoing LDL apheresis therapy. 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 Praluent 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. (NCT02326220)

Latest news:

• • On August 29, 2016, Sanofi and Regeneron Pharmaceuticals announced detailed positive results from ODYSSEY ESCAPE, a Phase 3 trial which evaluated Praluent® (alirocumab) Injection in patients with heterozygous familial hypercholesterolemia (HeFH) who require regular weekly or bi-weekly apheresis treatment. The trial demonstrated that adding Praluent® to existing therapy reduced LDL cholesterol by approximately 50 percent from baseline (compared to 2 percent increase for placebo). Praluent® significantly reduced the need for apheresis treatment by 75 percent compared to placebo (p<0.0001), the primary endpoint of the study. Results will be presented at a Hot Line session at the ESC Congress 2016 in Rome, Italy. Apheresis is a procedure similar to kidney dialysis where bad (LDL) cholesterol is removed from the blood, and is usually reserved for high-risk patients with very high cholesterol unable to achieve their cholesterol-lowering goals on any other therapy. Despite being treated with apheresis and entering ODYSSEY ESCAPE with very high LDL cholesterol levels (4.7 millimoles/liter [mmol/L] or 181 milligrams/deciliter [mg/dL]), nearly two-thirds (63 percent) of patients treated with Praluent® no longer required apheresis therapy after six weeks of receiving Praluent®. At this same time point, the average LDL cholesterol level among the Praluent®-treated group was 2.3 mmol/L (90 mg/dL), compared to 4.8 mmol/L (185 mg/dL) in the placebo group. European guidelines recommend LDL cholesterol target levels between 1.8-3.0 mmol/L (70-115 mg/dL), depending on cardiovascular risk. Other key results from ODYSSEY ESCAPE, which will be concurrently published in the European Heart Journal, include: Ninety-three percent of patients treated with Praluent experienced at least a 50 percent reduction in their apheresis procedures (p<0.0001). Throughout the trial, patients treated with Praluent experienced significant reductions in their LDL cholesterol starting at week 6 (55 percent greater reduction compared to placebo), and lasting until the trial ended, at week 18 (46 percent greater reduction compared to placebo) (p<0.0001). A similar proportion of patients experienced adverse events (AEs) in both the Praluent and placebo groups (76 percent both groups). The most common AEs (occurring in at least 5 percent of the Praluent group) were: fatigue (15 percent Praluent; 10 percent placebo), nasopharyngitis (10 percent Praluent; 10 percent placebo), diarrhea (10 percent Praluent; 0 percent placebo), myalgia (10 percent Praluent; 5 percent placebo), upper respiratory infection (7 percent Praluent; 19 percent placebo), headache (7 percent Praluent; 5 percent placebo), arthralgia (7 percent Praluent; 10 percent placebo), and back pain (5 percent Praluent; 10 percent placebo).
• • On March 23, 2016, Regeneron Pharmaceuticals and Sanofi announced positive results from the Phase 3 ODYSSEY ESCAPE trial evaluating Praluent® (alirocumab) Injection in patients with heterozygous familial hypercholesterolemia (HeFH), whose cholesterol levels required chronic, weekly or bi-weekly apheresis therapy. The trial met its primary endpoint, demonstrating that patients who added Praluent® to their existing treatment regimen significantly reduced the frequency of their apheresis therapy by 75 percent, compared to placebo (p less than 0.0001). Sixty-three percent of patients treated with Praluent no longer required apheresis, compared to zero percent of placebo patients. Apheresis is a procedure where bad (LDL) cholesterol is removed from the blood, in a process similar to kidney dialysis. The most common adverse events in the trial were fatigue (15 percent Praluent; 10 percent placebo), nasopharyngitis (10 percent Praluent; 10 percent placebo), diarrhea (10 percent Praluent; 0 percent placebo), myalgia (10 percent Praluent; 5 percent placebo), upper respiratory infection (7 percent Praluent; 19 percent placebo), headache (7 percent Praluent; 5 percent placebo), arthralgia (7 percent Praluent; 10 percent placebo), and back pain (5 percent Praluent; 10 percent placebo). Detailed data will be presented at future medical congresses.

Is general: Yes