New drugs and biologics channelled through the US Food and Drug Administration’s (FDA) fast-track programme spend longer than average in clinical development but gain considerably when they are filed for approval, a new study has found.

According to the analysis by the Tufts Center for the Study of Drug Development, the average clinical development time for 344 product candidates that received at least one fast-track designation from the FDA between January 1998 and June 2008 was 64.7 months. This was 5.7% more than for all drugs and biologics, which were in development for an average of 61.2 months.

Yet the cumulative development and approval time for fast-track products during this period was an average of 73.1 months, 5.1% shorter than the 77.0 months for all drugs and biologics. The difference was much faster review times when the products were submitted for FDA approval. At 8.4 months on average, these were 46.8% shorter than the 15.8 months for all drugs and biologics filed for approval (the review times refer to products that began clinical testing in 1992 or later and were cleared by the FDA between 1998 and 2007).

The cumulative improvement did not apply across the board. For cancer therapies, which secured by far the largest portion (around 35%) of the 395 fast-track designations in the 10 years reviewed by the Tufts Center, combined development and approval times were 81.0 months versus 81.4 months for all drugs and biologics.

The slower progress of fast-tracked product candidates through clinical trials was down to the programme’s focus on challenging medical conditions, suggested Janice Reichert, study author and senior research fellow at the Tufts Center. “Since many drugs that receive fast-track designation are being developed to treat serious or life-threatening conditions, such as AIDS, breast cancer and leukaemia, development hurdles are significant,” Reichert commented.

The fast-track programme was authorised by the Food and Drug Administration Modernization Act of 1997. The aim was to facilitate the development and accelerate the regulatory review of drugs and biologics for serious and life-threatening conditions, where these had the potential to address unmet medical needs. There is a particular emphasis in the programme on early and close communications between the product sponsor and the FDA to improve the efficiency of product development.

Stronger take-up

Take-up of the fast-track initiative has increased sharply in recent years, the Tufts Center reported in its September/October Tufts CSDD Impact Report. The number of designations more than doubled from 22 on average per year in 1998-2002 to 49 per year in 2003-2007. The bulk (70%) of these product candidates were small-molecule therapeutics but there were also biologics, vaccines and a diagnostic. Prophylactic and therapeutic vaccines received 9% of all designations, including five for anticancer vaccines and 19 for anti-infective vaccines.

The Tufts analysis also found that fast-track indications were more likely to be terminated during clinical trials and were less frequently approved than other product indications during the review period. At the same time, fast-track candidates were often developed for additional indications outside the programme.

Most fast-track candidates were abandoned for efficacy reasons, which were cited in 73% of terminations during 1998-2002 and 49% of terminations during 2003-2007. In 78% of cases this decision was taken during Phase III trials and in 86% of cases during FDA review. So far, the Tufts Center noted, just 2% of products granted a fast-track designation in 2003-2007 have been terminated during FDA review, as opposed to 29% in 1998-2002.

However, the majority of product candidates that entered the programme in 2003-2007 are still in clinical trials and they generally acquired fast-track status at an earlier stage of development, the Center pointed out. Only 10% of these products received a fast-track designation when they were already in late development, compared with 21% of candidates that entered the programme in 1998-2002.

This suggests that success rates for candidates granted a fast-track designation during 2003-2007 may ultimately be lower than for those in the 1998-2002 cohort. Meanwhile, the probability of moving from Phase I to Phase II clinical trials has been close to 100% for product candidates in both cohorts, “reflecting the fact many tend to receive fast-track designation after proof-of-concept studies” , the Tufts Center said.