治験薬はスタチンと共に作用しコレステロールを低下させる（Presentation #2123）

ODYSSEY COMBO II：Alirocumabはエゼチミブのコレステロール低下作用を上回る

ODYSSEY COMBO II: Alirocumab outshines ezetimibe for lowering cholesterol

心血管疾患（CVD）リスクの高い高コレステロール患者において治験薬alirocumabを標準的なスタチン療法に併用することにより、エゼチミブよりもコレステロールレベルが有意に改善したとのODYSSEY COMBO IIトライアルの結果が2014年European Society of Cardiology Congressホットラインセッションで発表された。AlirocumabはPCSK9（前駆蛋白質転換酵素サブチリシン/ケキシン9）阻害薬―標準的なコレステロール降下薬と相乗的に作用すると考えられている新しいクラスの薬剤―である。スタディには高コレステロール血症および他の心血管疾患リスクを有し、既に1日の最大用量のスタチンを内服しており忍容性のある患者720人（62歳前後）を対象とした。彼らはalirocumabの皮下注射（1回75～150mgを2週間おき）を受ける群（479人）またはエゼチミブ錠（1日10mg）を104週間投与される群（241人）にランダムに割り付けられた。エゼチミブと比較し、alirocumabは24週までおよび52週までにLDL-Cレベルを有意に低下させた（それぞれ50.6%対20.7%、 p<0.0001；49.5%対18.3%、p<0.001）。同様に、alirocumab治療患者の77%が24週までにLDL-C値 1.81 mmol/L [70 mg/dL]以下を達成したのに対し、エゼチミブ治療群では45.6%であった（p<0.0001）。

The investigational drug alirocumab significantly improved cholesterol levels compared to ezetimibe, when added to regular statin therapy in patients with high cholesterol and elevated risk of cardiovascular disease (CVD), according to the ODYSSEY COMBO II trial, presented as a Hot Line at ESC Congress 2014.

"The findings suggest that adding alirocumab to established statin regimens may provide an important new option to achieve needed reductions in low-density lipoprotein cholesterol (LDL-C) levels in high risk patients," said the study's principal investigator, Christopher Cannon, M.D., from the Harvard Clinical Research Institute in Boston, Massachusetts, USA.

Alirocumab is a PCSK9 (proprotein convertase subtilisin / kexin type 9) inhibitor - a new class of drug that is believed to work synergistically with traditional cholesterol-lowering therapies, he explained.

The study included 720 patients (aged approximately 62 years) with high cholesterol or other risks of cardiovascular disease, and who were already receiving a maximally tolerated daily statin dose.

The patients were randomized to receive either alirocumab (n=479) by subcutaneous injection (75-150 mg once every 2 weeks) or ezetimibe (n=241) as a pill (10 mg daily) for a period of 104 weeks.

All subjects were also assigned to a placebo treatment, either a pill (in the active alirocumab group) or an injection (in the active ezetimibe group) in order to maintain blinding.

The study showed that, compared to ezetimibe, alirocumab lowered LDL-C levels significantly more by week 24 (50.6% vs. 20.7%, P<0.0001) and by week 52 (49.5% versus 18.3% respectively at 52 weeks (P<0.001).

Similarly 77% of alirocumab-treated patients achieved LDL-C levels of 1.81 mmol/L [70 mg/dL] or lower by week 24 compared to 45.6% of ezetimibe-treated patients (P<0.0001).

Treatment-emergent adverse events (TEAEs) occurred in 71.2% of alirocumab patients and 67.2% of ezetimibe patients, leading to discontinuation in 7.5% and 5.4% respectively.

"This trial evaluated a 75 mg initial dose of alirocumab, which could be increased to 150 mg if needed," noted Dr. Cannon. "However, more than three-quarters of patients were able to reach target LDL-C levels at the initial dose without the need to up-titrate."

The study was funded by Sanofi and Regeneron.

Dr. Cannon has received grants from Accumetrics, Arisaph, Astra Zeneca, Boehringer-Ingelheim, and Janssen; grants and consulting fees from GlaxoSmithKline, Merck, and Takeda; and consulting fees from BMS, CSL Behring, Essentialis, Lipimedix, Pfizer, Regeneron and Sanofi.