读医学网

Genoa制药8月6日宣布，FDA已授予GP-101（吡非尼酮气雾剂，aerosol pirfenidone）治疗特发性肺纤维化（IPF）的孤儿药地位。

口服吡非尼酮（品牌名Esbriet）已被证明能够减缓IPF病情的恶化。然而不幸的是，需要非常大的口服剂量才能够实现有效的肺部药物浓度。尽管已确立了吡非尼酮的上限安全阈值（801mg TID，即：801毫克，每天3次），但通过口服给药所能递送的肺部剂量太低，而不能实现最佳的疗效。此外，口服吡非尼酮后的胃肠暴露及其血液水平的耐受性很差。由于这些原因，通过提高口服剂量来获得最佳IPF治疗效果是不可能实现的。此外，还有其他一些复杂的问题，如食物对药物的吸收、首过代谢、安全性所致的剂量减少、停药方案等，进一步降低了药物的肺部剂量以及维持治疗的中断。

为解决口服的缺点并使IPF疗效最大化，Genoa公司对吡非尼酮的配方进行了改造，开发了一种新颖的吸入性吡非尼酮（GP-101），能够产生吡非尼酮气雾剂并将其直接递送至肺部。通过这种方法，非常小剂量的吸入性吡非尼酮便可实现与口服吡非尼酮（Esbriet）相当的IPF疗效（5mg vs 801mg，剂量降低160倍）。鉴于如此小的吸入性剂量，口服吡非尼酮时存在的安全性和耐受性问题便迎刃而解，从而提高患者的依从性，并有望提高吸入性剂量实现优越的IPF疗效。除了作为一种疗效改善的Esbriet替代品，GP-101作为一种安全和良好耐受性的吸入性产品，有望与其他药物（如勃林格殷格翰的IPF新药nintedanib）联合用药。

特发性肺纤维化（IPF）是一种常见的特发弥漫性肺纤维化疾病,是慢性非肿瘤呼吸系统疾病中预后最差的一种疾病。其主要症状是进展性呼吸困难和肺功能不可逆损害。许多患者以渐进性呼吸急促,躯体残疾,急性恶化为发病特征,确诊数年内患者就可能会死亡,死亡率甚至高于许多癌症。很显然,改善呼吸质量,提高存活期是目前此病的主要治疗目标。（生物谷Bioon.com）

英文原文：

Genoa Pharmaceuticals Receives Orphan-Drug Designation for Pirfenidone in the Inhaled Treatment of Idiopathic Pulmonary Fibrosis (IPF)

San Diego, CA – August 5, 2014 – Genoa Pharmaceuticals, the leader in inhaled medicines for pulmonary fibrosis, today announced the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to Genoa for the use of pirfenidone in their lead program – inhaled GP-101 for the treatment of IPF.

Acquiring orphan status marks an important regulatory milestone in GP-101’s life cycle to treat people with this devastating disease,” said Mark Surber, Ph.D., Genoa’s President and Chief Executive Officer. We are pleased to continue the development of inhaled GP-101, with clinical trials beginning in early 2015.

Oral pirfenidone (Esbriet?) has shown promise to slow IPF disease progression. Unfortunately, a very large oral dose is required to achieve efficacious lung levels. Despite being established at the upper safety threshold (801 mg TID), the resulting oral-delivered lung dose is too low for optimal effect. Moreover, gastrointestinal exposure and large-associated blood levels remain poorly tolerated. For these reasons oral-dose escalation for optimal IPF efficacy is not possible. Complicating matters, dose-absorbing food, first-pass metabolism, and safety-driven dose-reduction and stoppage protocols further reduce lung dose and interrupt maintenance therapy.

To address oral shortcomings and maximize IPF efficacy, Genoa has reformulated pirfenidone for aerosol formation and inhaled, direct-lung delivery (GP-101). By this approach, ~160-fold less inhaled pirfenidone is predicted to deliver Esbriet-equivalent IPF efficacy (5 mg vs. 801 mg). With such a small inhaled dose, remaining safety and tolerability concerns may be eliminated, enabling improved patient compliance and an increased inhaled dose for superior IPF efficacy. In addition to serving as an improved-effect Esbriet replacement, a safe and well-tolerated inhaled product is expected to enable desired, but otherwise poorly-tolerated combination regimens (e.g., with Boehringer Ingelheim’s Nintedanib).

About Orphan Drug Designation

Orphan drug designation is a status assigned to a medicine intended for use in rare diseases. In the U.S., the Orphan Drug Designation program provides orphan status to medicines intended for the safe and effective treatment or prevention of rare diseases that affect fewer than 200,000 people. In the E.U., a medicine must meet similar criteria, affecting up to five in 10,000 people. Orphan designation for inhaled GP-101 will be pursued in the E.U. with clinical data. Orphan status provides sponsors with development and commercial incentives, including 7 and 10 years market exclusivity for these two regions, respectively.

About IPF

IPF is a fatal lung disease caused by both genetic and environmental factors resulting in progressive lung scarring and death due to respiratory failure and/or co-morbidities. Characterized by a dry cough, shortness of breath and decreased exercise capacity, this disease exhibits a post-diagnosis survival period of ~2-5 years, annually killing more people than breast cancer. As fibrosis is at present irreversible, an efficacious product will provide a well-tolerated stand-alone or combination maintenance therapy that protects healthy lung tissue against invading fibrosis or meaningfully slows disease progression.

About Genoa Pharmaceuticals

Genoa Pharmaceuticals, Inc. is committed to developing improved therapies for the treatment of IPF. Based in San Diego, Genoa’s lead program, GP-101 (aerosol pirfenidone) plans to enter clinical trials in early 2015.