Keeping up with its workload and approving novel drugs is not enough to ensure that a steady stream of truly innovative medicines reaches patients; FDA recognizes that it should do more to help in the early phases of drug development that have the highest failure rates.

Over the years FDA has repeatedly pointed out that it can only review what comes to it – that the drop in novel drug approvals has more to do with the number of applications coming in than any change in leniency by agency reviewers. Though annual approval numbers are up for the past few years, at the beginning of the slump in the early-mid 2000s, FDA officials argued that the low numbers were the result of waning pipelines, not agency blockage Also see "NDA Filing Slowdown Continues; FDA Has Received 16 NMEs In FY 2002" - Pink Sheet, 16 September, 2002..

In recent years, and as the fifth round of the Prescription Drug User Fee Act was being negotiated, CDER Director Janet Woodcock has pointed out that FDA review is also the most predictable segment of drug development. The failure rate at FDA is 22%, while attrition in earlier stages is much higher: 38% in Phase I, 68% for Phase II and 45% for Phase III, according to data presented by FDA in 2011 Also see "FDA Still Most Predictable Part of Drug Development, Despite Bumps, Woodcock Says" - Pink Sheet, 1 June, 2011..

In its FY 2012 Innovative Drug Approvals report, released Dec. 5, the agency acknowledges that in addition to its marketing authorization and post-market surveillance functions, “it must also help sustain biomedical innovation in the U.S.”

Though the premarket review phase draws the most attention, it is not the biggest hurdle in getting a new drug to market, and greater impact can be had by focusing on earlier stages of drug development.

“Increases in research and development expenditures are not being matched by increased discovery of innovative drugs,” the report states. “Serious public health needs, such as autism and Alzheimer’s disease, are not yet being met by new drug innovation, despite years of research and investment. An environment that supports pharmaceutical innovation depends not just on efficient FDA review, but on improving the efficiency and success of the earlier stages of drug development.”

FDA believes its contributions to that through improvements in regulatory science, which it describes as the development of scientific tools that can bridge the gap between cutting-edge discoveries and real-world diagnostics, treatments and cures – though industry wants to be involved as well Also see "Industry Seeks Bigger Role In Tackling Regulatory Science" - Pink Sheet, 31 October, 2011..

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The agency’s efforts to increase use of genetic data and qualified biomarkers is an example, as are a number of projects “internally and through collaborations with industry, academic, other regulatory agencies, consumers, researchers and others to help increase the efficiency and success of earlier phases of drug development” (see sidebar).

Innovation By The Numbers

FDA notes that the 35 innovative drug approvals in FY 2012 – matching the number for FY 2011 – were “notable for their efficiency and timeliness,” in part due to existing programs to facilitate development and review. That too was an echo of FY 2011 Also see "FDA Initiatives To Expedite Reviews Pay Off In FY’11 Approvals" - Pink Sheet, 1 November, 2011..

“All but one of the 35 novel drugs (97%) met PDUFA target dates, surpassing the PDUFA goal of reviewing and acting on 90% of NMEs by their target dates,” the report states, and 77% were approved on the first review cycle.

The agency’s various expedited review programs came into play for just over half of the FY 2012 cohort. Twelve of the 35 received a fast track designation and two were accelerated approvals. Twelve (51%) received priority review, and of those, 11 (92%) were approved on the first cycle.

FDA noted that with the “breakthrough designation” put in place by PDUFA V, it will have a new tool to expedite development of therapies that show substantial promise in early clinical trials; drugs with that status will get advice and interaction throughout the development process to streamline the trials and review period. One drug has already been designated a breakthrough, though the specifics of the program are still in the works Also see "“Breakthrough Therapy” Development Speed May Be Tempered By Manufacturing Hurdles" - Pink Sheet, 26 November, 2012..

Other elements of PDUFA V, or the FDA Safety and Innovation Act, are also focused on increasing early communication – which the agency agrees can make a difference in a drug’s chances for approval. But the FY 2012 Innovative Drug Approvals report points out that such communication is already in place (for instance, under the fast track program) and is having an impact. “Strengthened communication with drug companies early in development and flexible clinical trial designs for drugs with unmet medical needs also enabled drug companies to conduct shorter, smaller, or fewer studies, reducing the length and cost of drug testing,” the report states.

It notes that in rare diseases, “FDA often allows non-traditional approaches to establishing safety and effectiveness.” For example, the approval of BTG PLC’s Voraxaze to treat the small population of cancer patients who develop toxic methotrexate levels in their blood was based on data from 22 patients in a single clinical trial Also see "BTG Gains First U.S. Approval With Methotrexate Antidote Voraxaze" - Pink Sheet, 18 January, 2012.. Nine of the FY 2012 approvals were for orphan diseases; over the last five years, approximately one-third of NMEs have been for rare diseases.

The report also highlights FDA’s efficiency as compared to other regulatory agencies. “Of the 32 novel drug approvals that FDA was able to compare to approvals in other countries, 75% (24/32) were first approved in the U.S.” All fast-track drugs were approved first in the U.S., compared to 64% in 2011.

FDA Wants To Help You Develop Drugs

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