尼达尼布和吡非尼酮获准用于肺纤维化治疗

美国食品药品管理局（FDA）10月15日批准两种新的口服药物用于特发性肺纤维化治疗，分别为勃林格殷格翰的尼达尼布（nintedanib，商品名：Ofev）和罗氏的吡非尼酮（pirfenidone，商品名：Esbriet）。

据FDA称，在III期试验中，这两种药物与安慰剂相比，均可显著延缓患者用力肺活量（FVC）下降。FDA授予这两种新药快速通道、优先审评、孤儿药以及突破性药物认定资格，并均提前获批。据生产商称，这两种药物在2周内均将上市。

吡非尼酮已在欧洲和加拿大上市。罗氏称，该公司计划出台“一套全方位患者支持项目，旨在有助于药品可及、经济资助和持续教育。”

对于尼达尼布，勃林格殷格翰计划出台“一套综合患者支持项目，以提供广泛的经济和护理支持服务，”称其为“开放门户（Open Doors）”。在试验中，尼达尼布与安慰剂相比最常见严重不良反应为支气管炎（1.2% vs. 0.8%）和心梗（1.5% vs. 0.4%）。肺炎（0.7% vs. 0.6%）、肺癌（0.3% vs. 0%）和心梗（0.3% vs. 0.2%）是最常见致命性不良事件。

尼达尼布最常见副作用包括腹泻、恶心、腹痛、呕吐、肝酶升高、食欲下降、头痛、体重下降和高血压。FDA称，不推荐该药物用于中至重度肝病患者或孕妇，该药物属于孕妇用药分级D类，育龄女性至少在停药3个月内采取避孕措施。

吡非尼酮与安慰剂相比，最常见严重不良事件为肝酶升高（3.7% vs. 0.8%）、对光敏感或皮疹（9.0% vs. 1.0%）以及胃肠道副作用（导致中断治疗患者比例分别为2.2%和1.0%）。

吡非尼酮最常见副作用为恶心、皮症、腹痛、上呼吸道感染、腹泻、乏力、头疼、消化不良、头晕、呕吐、食欲下降、胃食管返流、鼻窦炎、失眠、体重下降和关节痛。

FDA警告重度肝病、终末期肾病或需要透析的患者不要服用吡非尼酮。吡非尼酮服用者还应进行监测且避免阳光暴露。

罗氏称，吡非尼酮临床试验共纳入1,247例特发性肺纤维化患者。在纳入555例患者的一项试验中，吡非尼酮用药患者1年后FVC下降至少10%的比例为17%的，而安慰剂为32%。

勃林格殷格翰称，尼达尼布试验共纳入1,231患者。在纳入513例患者的一项试验中，1年后年FVC下降相对减少52%（-115 vs. -240）。

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 By: M. ALEXANDER OTTO, Internal Medicine News Digital Network

The Food and Drug Administration on Oct. 15 approved two new oral medications for idiopathic pulmonary fibrosis, BoehringerIngelheim’s nintedanib (Ofev) and Roche’s pirfenidone (Esbriet).

The drugs significantly slowed the decline of forced vital capacity (FVC), compared with placebo, in phase III testing. They did not significantly reduce mortality. The FDA granted both agents fast track, priority review, orphan product, and breakthrough designations. Both were also approved ahead of schedule, according to the agency. Each of the drugs should be available for patients within the next 2 weeks, according to their manufacturers.

For pirfenidone, already on the market in Europe and Canada, Roche said it plans “a comprehensive patient support program designed to help with access, financial support, and ongoing education.”

For nintedanib, BoehringerIngelheim plans “a comprehensive patient support program that will provide a broad range of financial and nursing support services,” called “Open Doors.” In testing, the most frequent serious adverse reactions with nintedanib, versus placebo, were bronchitis (1.2% versus 0.8%) and myocardial infarction (1.5% versus 0.4%). Pneumonia (0.7% versus 0.6%), lung cancer (0.3% versus 0%), and MI (0.3% versus 0.2%) were the most common fatal adverse events.

The most common side effects of nintedanib were diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight loss, and high blood pressure. Nintedanib is not recommended for patients who have moderate to severe liver problems or are pregnancy class D. Women of childbearing potential should use contraception for at least 3 months after stopping the drug, according to the FDA.

For pirfenidone, the most serious adverse events versus placebo were liver enzyme elevations (3.7% versus 0.8%), sensitivity to light or rash (9.0% versus 1.0%), and gastrointestinal side effects that caused 2.2 % of patients to discontinue treatment compared with 1.0% of those who received placebo.

The most common side effects of pirfenidone were nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, loss of appetite, gastroesophageal reflux, sinusitis, insomnia, decreased weight, and arthralgia.

The FDA warned about use of pirfenidone in patients with severe liver problems or end-stage kidney disease, or in those who require dialysis. Patients taking pirfenidone also must monitor and guard against sun exposure.

Clinical trials of pirfenidone included 1,247 idiopathic pulmonary fibrosis patients. In one with 555 patients, 17% of pirfenidone patients had an FVC decline of at least 10% after a year, compared with 32% who received placebo, Roche said.

Trials of nintedanib included 1,231 patients. One with 513 showed a relative reduction in annual FVC decline of 52% (–115 versus –240 mL for placebo) at 1 year, BoehringerIngelheim noted.