Although big pharma companies continue to search for solutions to R&D sourcing and productivity challenges, 2013 ranks among the top 4 approval years since 2004. A recent report from Evaluate (source: EPVantage “FDA Approval Rates Niche products driving record success”, 2013) shows that the total potential value of the class of 2013 is $18.7bn five years after launch, a 14% increase on the five-year post launch expectation of the drugs approved in 2012.
2013 was also the year of the new “breakthrough therapy” designation (3 drugs approved), which adds to the FDA’s current arsenal to accelerate the approval process to address high unmet medical needs.
2012’s sudden uptick of new approvals, a 16-year high, coupled with FDA efforts to expedite certain applications suggested an R&D revival, but this premise did not fully play out in 2013. Among other things, the FDA linked the drop in approvals in 2013 to a decline in new drug applications (32 filed in 2013 versus 41 in 2012). Over the years, with the exception of 2007, spikes in submissions have been mirrored in the approval numbers (Exhibit 2).
Looking below the surface, 44% of approved treatments were the result of at least one expedited approval process (Priority approval, breakthrough therapy, and/or accelerated approval). Since 1988, the FDA has sought new methods to supplement the standardized approval process, should the existing pathways prevent urgent access to treatment. The fast track designation was created in 1988, followed by accelerated approval (1992), and priority review (1992). In July 2012, the FDA created the breakthrough therapy designation, to be used:
“If the drug is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.” (Source: Section 506(a) of the FD&C Act)
For all of these designations, the FDA is expected to work closely with drug sponsors to accelerate timelines. For example Gyzyva was approved in 6.3 months (Breakthrough and priority review), Xofigo in 5 months (Fast track and priority review), and Imbruvica in 4.5 months (Fast track, breakthrough, priority review, accelerated approval). In comparison, between 1993 and 2011, half of the approved treatements took eight or more months for approval (Source: CDER, “CDER New Drug Review 2012 Update).
By the end of 2013, the FDA Center for Drug Evaluation and Research (CDER) received 120 requests for breakthrough therapy designation, resulting in 37 designations, 58 denials, and 3 approvals (the remaining applications were withdrawn). Unlike the fast-track designation, breakthrough therapies can apply to therapeutic areas where treatments already exists, demonstrating the FDA’s willingness to expand both the breadth and the depth of the standard of care for life-threatening illnesses. There has been a greater, but stabilizing, proprotion of approvals gained through these pathways over recent years (Exhibit 3).
The most common reasons for denial of a breakthrough designation were based on clinical presentation, including:
- Evidence does not include clinical data
- Evidence is too preliminary to be considered reliable
- No demonstration of “substantial” improvement over available therapy
- Reliance on novel biomarker or surrogate endpoint without sufficient evidence to support benefit to patient
- Post-hoc analysis of failed studies that identified a subset that may benefit
As the FDA continues to test new pathways (e.g. Biomarin’s Vimizim received a “Rare Pediatric Disease Priority Review Voucher” designation in Feb 2014), pharma companies will keep on gearing innovation towards areas of high unmet needs (e.g. oncology, orphan diseases) with the hope of maximizing probability of regulatory success and reducing time to market.
In our next post about FDA approvals, we'll discuss therapeutic trends.