Pipeline Execution

Parexel consulting just published a new white paper highlighting the key limiting factors in getting new drugs to approval. The paper focuses on perhaps the 2 most critical factors shaping the pharmaceutical industry’s future performance at a time when R&D costs continue to rise in relation to output and ‘safety first’ becomes the dominant principle in the US regulatory environment. The most pressing challenge for industry executives “has shifted from building the pipeline to executing the pipeline”, it comments. The hurdle has resulted in a decade long decrease in submissions of New Molecular Entities (NME's) in the US. After averaging 45+ per year in the mid-1990s, NME filings to the FDA dropped to 21 in 2006. Last year they recovered slightly to 28 submissions. The preliminary results of an FDA study on NMEs released in June indicated that the overall decline may reflect industry’s waning interest in seeking approval for less innovative NMEs.



First Cycle Approval

How much is getting a new drug through the FDA approval process at first attempt worth? About $639.2 million according to Parexel. For NMEs signed off by the FDA in 2007 and the first half of 2008, the approval times for compounds cleared in a single review cycle were less than one third those for NMEs requiring resubmissions (8.6 months versus 27.7 months).

The good : there has been a recent increase in the percentage of US NDAs gaining first-cycle approvals. In the 2006 fiscal year cohort (the latest to mature fully), the FDA’s Center for Drug Evaluation and Research set a record for the user-fee era of approving 51% of NDAs in the first review cycle.

The bad: In FY 2007, nearly a quarter of Class 1 NDA submissions – the less complex refilings in response to minor issues raised in the first-cycle review – failed to gain approval.

The ugly: Close to two-thirds of Class 2 NDA resubmissions – typically filed in response to more significant questions arising in the initial or previous review cycle – during FY2007 did not make it to approval.

Priority Review

Priority review status – usually reserved for drugs with indications where there are no satisfactory alternatives or that offer significant improvements over what is already available- is the second most critical factor that directly correlates with revenue loss. Nearly US$448.4 million worth .

The FDA’s performance goals specify six months for taking action on priority NDAs, compared with 10 months for standard NDAs, the white paper notes. However, the implications of a priority rating are “far more significant” – for example, between 1 January 2006 and 30 June 2008, priority NMEs were cleared on average 13 months ahead of standard-rated NMEs.

Moreover, 94% of the priority NMEs approved in 2006, 2007 and the first half of 2008 were cleared in the first review cycle, while around one quarter of all standard NMEs approved over the same period needed three cycles to get through the process. To make matters worse after granting priority ratings to 30% of the NDAs submitted in 2005, the agency has done so for only 18% of applications filed in FY 2007 and up to 31 March 2008.