FDA is Increasingly Approving Drugs Based on One Clinical Trial Only 
[Thursday, May 16, 2019]

It has been a common assumption that one must conduct two or more pivotal clinical trials to support the NDA or BLA for a new drug or biologic. But it is not true. About a third of NDA and BLA applications for new products approved by FDA in 2018 were based on one clinical trial only. A recent review discussed several trends in new drug development over the last 10 years that debunk several such commonly held myths about FDA approval. For example, small companies with seemingly limited resources hold on more than 70% of the new drugs in development and these companies took their products all the way to market approval. About half of all drug approvals by FDA were based on clinical trials conducted in a total of less than 500 patients; some drugs approved based on clinical trials only in 200 or less patients. There was also an NDA approval in 2018 based on data from one trial conducted entirely outside the US. Some findings were expected such as that about half of the drugs approved by FDA were for orphan indications, about a third of all drugs approved were first-in-class molecules, and that more than 70% of new drugs approved had one or more expedited approval designations. It was also confirmed that about half of the new drugs approved were for oncology and infectious diseases, and that accelerated approval and breakthrough therapy designations lead to faster approvals. These trends present a highly modernized regulatory environment where FDA is increasingly willing to bend conventions to support new treatments for diseases with few or no treatment options. It also presents an industry that is increasingly efficient at exploiting the various regulatory pathways to reduce the time to market. Also, this has helped smaller developers to not depend on big companies to acquire them and get their products to market but be able to do it on their own and even commercialize products, adding to the available exit options.  And these trends are here to stay. It is expected that clinical trial data requirements for product approvals with further decrease with the use of real world data along with clinical trial data, digital tools, new endpoints based on patient reported outcomes, target drug development, precision medicine, and better recruitment strategies. Overall the review paints a very positive picture for the FDA-industry liaison. The review provides several pointers about developing new treatments  highlighting the opportunities and challenges in developing new drugs and biologics. Although the review did not touch upon medical devices, the similar trends, in principle, have existed for devices as well with an increasingly flexible and agile FDA as has been seen for developers of devices based on software, AI, and innovative technologies.