Pharma & Healthcare 4/15/2015 The FDA on Wednesday approved ivabradine (Corlanor), Amgen's new heart failure drug. The drug has been available for several years in Europe, where it is sold by Servier under the brand names of Corlentor and Procoralan. Ivabradine was approved for the reduction of hospitalization from worsening heart failure. It is indicated for use in stable heart failure patients who are in sinus rhythm, have a resting heart rate of at least 70 bpm, and who are also taking the highest tolerable dose of a beta blocker. Ivabradine slows the rate of the heart by inhibiting the so-called "funny" current within the heart's natural pacemaker, the sinoatrial node. The drug received an expedited review under the FDA's priority review program. Approval was based on results of the SHIFT trial, published in 2010, which studied 6,558 patients with heart failure who had a heart rate > 70 bpm. After a median 22 months of followup, the rate of cardiovascular death or hospital admission for worsening heart failure was 24% in the ivabradine group and 29% in the placebo group (HR 0.82, 95% CI 0.75–0.90, p<0.0001).The FDA said that that the most common side effects of the drug were bradycardia, hypertension, atrial fibrillation, and temporary vision disturbance (flashes of light). The FDA said that ivabradine can cause harm to fetuses and that women should not become pregnant while taking it.In Europe ivabradine has been approved for use for both heart failure and stable angina. In 2014results from a 19,000 patient stable angina trial,SIGNIFY, prompted the European Medicines Agency (EMA) to make several recommendations intended to lower the risk of heart problems linked to the drug. Although the overall results of SIGNIFY were neutral, troubling findings occurred in the very large subgroup (more than 12,000 patients) with symptomatic angina. The EMA review concluded that in these patients ivabradine, compared with placebo, had a small but significant increase in the risk of CV death and nonfatal MI (3.4% vs 2.9% yearly incidence rates) and a substantially higher risk of bradycardia (17.9% vs. 2.1%). The EMA said ivabradine was also associated with an increased risk for atrial fibrillation. SIGNIFY tested a higher dose of ivabradine, but the EMA concluded thatthe high dose "did not fully explain the findings."
Ivabradine 的相對療效: 實證為樞紐試驗 SHIFT (Systolic heart failure treatment with If inhibitor ivabradine Trial)，其結果在主要療效指標--降低心血管死亡率或因心臟衰竭惡化住院(複合性指標)比例的表現，ivabradine 組顯著優於安慰劑組。但 SHIFT 試驗中所 納入受試者條件與我國許可適應症並不完全相符，僅供參考。另，於廠商送審資料中所 提出之未公開發表數據，整體來說，對於使用β阻斷劑屬禁忌症的病人，ivabradine 治 療在主要療效指標與次要療效指標部分，均獲得具統計顯著之結果。
1. SHIFT 試驗：Ivabradine 比較安慰劑 為一項為期三年的隨機、雙盲、安慰劑對照、多國多中心臨床試驗，在同時服用其他治療心臟衰竭藥物的情況下，以 ivabradine 治療中重度慢性心臟衰竭以及左心室收縮功能障礙病人時的療效。主要療效指標為 ivabradine 降低心血管 死亡率或因心臟衰竭惡化住院(複合性指標)比例的表現。 共有 6505 位病人進入試驗隨機分派階段，其中 3241 位接受 ivabradine 治療。 受試者的追蹤期(中位數)為 22.9 個月，接受試驗藥物治療的時間(中位數)為 21.6 個月。 主要療效指標發生率 ivabradine 組顯著低於安慰劑組(24.5% vs. 28.7%)，對應 於 18%的相對風險降低(hazard ratio 0.82, 95% CI 0.75-0.90, P<0.0001)。
2. 在文獻搜尋過程中，查無與我國適應症完全相符之已發表文獻可供參考，廠商於送 審資料中所提出之部分數據(未公開發表)，基於保密原則，無法於此處詳實呈現。 整體來說，對於使用β阻斷劑屬禁忌症的病人，ivabradine 治療在主要療效指標與 次要療效指標部分，均獲得具統計顯著之結果。醫療倫理：查無醫療倫理相關之國內資料可供參考。成本效益：無本土決策情境之成本效果研究結果可供參考。
財務衝擊：在藥費財務影響方面，廠商預估 ivabradine 若納入健保給付，第 1~5 年之年度藥費約 460 萬元~1.28 億元。查驗中心認為建議者之分析架構及參數清楚合理，其分析結果可做為重要參考；且由於 ivabradine 屬於輔助治療(add-on therapy)，故其年度藥費也等同於年度藥費財務衝擊。若進一步考量使用 ivabradine 應可節省病人因心衰竭住院之醫療費用，廠商估計每年可節省心衰竭住院醫療費用 約 46 萬~1,300 萬元；查驗中心認為此處可能低估 ivabradine 節省之醫療費用。查 驗中心重新進行分析，預估 ivabradine 每年可節省心衰竭住院之醫療費用約 1,000 萬~2,900 萬元；合併計算 ivabradine 之年度藥費，查驗中心預估 ivabradine 每年造 成之整體財務衝擊約為 350 萬元~1.00 億元。
No comments:
Post a Comment