Most reports of pharmaceutical R&D productivity undercount the number of new drugs that reach the market each year, missing out on billions of dollars of sales, because they omit approvals from the Food and Drug Administration’s (FDA) biologics division, according to a new report by London-based research company EvaluatePharma.

According to the report, the majority of new drug approval counts in 2010 failed to include the year’s two most potentially valuable products, prostate cancer treatment Provenge and pneumococcal vaccine Prevnar 13, plus three other new agents that were approved by the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees new agents such as vaccines and blood plasma products.

Most trade publications, which use only numbers published by the FDA’s Center for Drug Evaluation and Research (CDER) division, cited 21 new approvals in 2010; adding CBER-approved products lifts last year’s total to 26.  The EvaluatePharma study found that 65 new biologics have gone largely uncounted during the past 12 years.

While the number of CBER-approved products is relatively small in any given year, Jonathan de Pass, chief executive of EvaluatePharma, said the examples of Provenge and Prevnar 13, along with other important approvals from the division including cervical cancer vaccines Gardasil and Cervarix and enzyme replacement therapy Cinryze, indicate that they should not be overlooked, particularly since counting annual FDA approvals is widely used to assess R&D productivity.

“With such intense scrutiny of pharmaceutical productivity at the moment, FDA approval rates are an important number to get right,” said de Pass. “Approvals by CBER are only going to become more important in the future, with advances in areas like gene therapy and the significant investment going into improved hemophilia therapies, for example.”

The omission of CBER approvals is particularly noticeable among the 2010 new drug counts since analysts believe Prevnar 13 and Provenge are likely to be the most commercially successful new products approved last year, with EvaluatePharma estimating U.S. sales of the two products at nearly $4.5 billion in the next five years. According to the report, of the $36.6 billion in sales added by new products during the last five years, $7.5 billion, or 20%, was derived from novel biologics approved by CBER. Aside from Prevnar 13 and Provenge, the biggest-selling CBER approvals in recent years include Menveo, Cinryze, Gardasil, Cervarix, Zostavax, RotaTeq and Rotarix.

Although the upgraded analysis does not improve the overall picture of declining R&D productivity, the report said as a greater number of high-value biologics are processed by CBER in the future, there should be more accurate measures of R&D productivity.

The Biotechnology Industry Organization (BIO), which provides advocacy and support to the industry worldwide, also wants innovative therapies approved by CBER appropriately counted in new drug approval reports. “Most trade publications will only count the CDER New Molecular Entity (NME) approvals. We agree that does undercount the number of innovative products that go to market, particularly when you are talking about vaccines, cell therapies or advanced tissue products, since many of those innovative products that are approved by CBER don’t make it into those annual tallies,” said Andrew Emmett, managing director of science and regulatory affairs at BIO. “We would certainly like to see an accurate representation of the output of innovation coming from industry. And just counting the CDER NMEs certainly doesn’t capture some very exciting product approvals that are taking place in CBER. While usually it’s only about three to five in a given year, we certainly believe that those products should be incorporated into the overall tally.”

However, devising a truer measure of innovation output raises difficult questions about how these innovative biologics should be defined.  “It’s something that we certainly think about from time to time. Whether the appropriate output is NMEs verses priority approvals targeting the greatest public health need, it’s difficult to cut it very clearly,” said Emmett. “We are not proposing anything different at this time. We recognize the challenge of defining innovation and defining innovative output.”

Each year, BIO does its own internal tally of approvals that includes CBER entities, which often requires judgment calls about which products represent true innovative advances. “We used to keep a list of approved biotech products on our web site,” said BIO’s Emmett. “Then we frankly found it very challenging to accurately describe an innovative biotech product. Is it created through traditional recombinant DNA methods? Or is it something that can be characterized using biotechnology methods? Is it something that is targeted for a certain genetic subtype, which would be utilizing biotech diagnostic methods? As the science evolves, it could be very difficult to draw bright lines.”

--Karyn Korieth