Food and Drug Administration, Office of Orphan Products Development, Silver Spring, MD 20993-0002, USA.
Pediatrics. 2010 Jul;126(1):101-6. doi: 10.1542/peds.2009-3246. Epub 2010 Jun 21.
The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs).
Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined.
We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003).
For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.
1983 年美国孤儿药法案建立了一个流程，通过该流程，有前途的疗法被指定为孤儿产品，并且在随后的安全性和疗效数据令人满意的情况下，获得营销批准和财政激励。我们考察了代谢性遗传病（IEM）药物开发方面的成就。
利用食品和药物管理局的数据来确定 IEM 的孤儿产品指定和批准，并总结过去 26 年的趋势。从提交新药研究申请到获得营销批准的各个临床开发时间（CDT）也被确定。
我们研究了 1983 年至 2008 年期间的 1956 个孤儿产品指定，发现其中 93 个（4.8%）用于 IEM。其中，24 个（25.8%）获得了营销批准。这一批准比例明显（P =.036）高于非 IEM 孤儿产品（17%）。在 IEM 产品中，复杂分子的疾病获得了最多的指定和批准（分别为 61 个和 11 个）。在亚组中，溶酶体贮积症获得了最多的指定和批准（分别为 43 个和 9 个），而除脂肪酸氧化障碍外的线粒体疾病获得了 7 个指定却没有获得批准。然后，我们检查了已批准的 IEM 产品的 CDT，发现中位数为 6.4 年（范围：2.6-25.1 年）。生物制品的 CDT 明显短于药物（平均值：4.6 与 11.0 年；P =.003）。
26 年来，孤儿药法案为 IEM 带来了新的治疗方法。为什么一些 IEM 促使了成功的药物开发，而另一些则没有，这仍然是个谜；然而，没有治疗方法的 IEM 患者的需求是确定无疑的。
