FDA surprises with fast approvals but can trend be sustained?

If the first month of 2012 is any indication, the FDA is out to set new records for approval times. The sanction yesterday of Vertex’s cystic fibrosis drug Kalydeco came 78 days before its PDUFA decision date, a verdict that closely followed backing for Roche and Curis’ Erivedge, which came 39 days early.

Whilst January’s results should not necessarily be seen as an indicator of full-year performance, it marks a departure from the showing of 2011, when approval times lengthened (see table). If there is any lesson to be taken, it is that candidates with compelling data and in unmet medical needs, like Kalydeco, tend to whip through the corridors of the FDA.

NME Approval Numbers and Time since 1999
Priority Review Standard Total
Year Number Average Time Number Average Time Number Average Time
2011 14 10.7 16 18.6 30 14.9
2010 10 9.4 16 14.1 26 12.3
2009 13 9.8 21 15.3 34 13.2
2008 9 10.4 22 19.4 31 16.8
2007 13 7.6 13 15.8 26 11.7
2006 13 7.2 16 22.2 29 15.2
2005 17 8.7 11 17 28 11.9
2004 16 12.5 22 27.1 38 19.6
2003 13 13.7 22 30.8 35 24
2002 9 25.1 17 25.8 26 25.6
2001 9 9.4 23 20.2 32 17.2
2000 8 6.4 25 23.8 33 19.3
1999 22 10 18 18.5 40 13.8

Lengthening timelines

Preliminary approval time data compiled by EvaluatePharma show that novel drugs approved in 2011 took on average 14.9 months to clear US regulatory hurdles, an increase on the 12.3 months of 2010; priority reviews took 10.7 months on average and standard reviews 18.6 months. This compares to the PDUFA guidelines of six months for priority reviews and 10 months for standard reviews.

However, it is important to note that 2011’s list included second-pass approvals for Firazyr, Xarelto, Arcapta Neohaler and the iron chelator Ferriprox, each taking 30 months or more to get the regulator’s stamp of approval. The process for the Shire hereditary angioadaema drug Firazyr stretched out to 46 months, after phase III studies had to be repeated. If the four that took more than 30 months to pass are excluded, the average review time is 11.6 months, in line with historical averages (FDA approval times continue to shorten, March 11, 2011).

On the other end of the spectrum, Zelboraf cleared in 3.6 months, Zytiga in 4.2 and Xalkori in 4.9 months. Each was in a relatively underserved area of oncology and as such had relatively low efficacy bars to leap on the way to final approval.

Similarly, January 2012 approvals Kalydeco and Erivedge, also known as vismodegib, are treatments for relatively unmet needs with solid data behind them. Kalydeco was shown to improve lung function in cystic fibrosis patients with the G551D mutation, a disease modifying therapy rather than providing symptomatic relief. Erivedge is the first nonsurgical treatment for advanced basal cell carcinoma.

Thus the FDA approval trends reinforce the industry’s focus of recent years, with orphan and cancer drugs viewed as having lower regulatory and commercial risk than the blockbusters of yesteryear (BIO 2011 – Orphan drugs unlikely to escape pricing pressures, June 28, 2011).

It will be some months before the FDA publishes its final count of novel drugs approved in 2011, so the tally of 30 remains preliminary. This number also does not include those drugs evaluated by the agency’s Center for Biologics Evaluation and Research, which reviews vaccines, blood products and some candidates that qualify as biologicals. Should the FDA deem Anascorp, Laviv, Kedbumin, Corifact and Ardovax new products, 2011 would have seen the US regulator approve 35 novel therapeutic agents.

Maintenance of effort

There is no guarantee that trends toward faster approvals will be sustained. As the EvaluatePharma statistics indicate, average approval times have ebbed and flowed since the turn of the century; indeed, the FDA’s own figures indicate that they have done so since the passage of the Prescription Drug User Fee Act (PDUFA) 20 years ago.

In addition, with the new PDUFA needing to pass by the end of the US fiscal year on September 30, there is a good chance that new procedures will be put in place that could slow the FDA’s approval process (PDUFA renewal takes shape with extended FDA reviews, June 1, 2011).

For an industry accustomed to regulatory delay the first month of 2012 should come as a pleasant surprise. But it is far too soon to say whether it can be sustained – the quality of new drug applications, the agency workload and coming changes to agency processes will affect that outcome.

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