The number of new molecular entities (NMEs) approved by the US Food and Drug Administration (FDA) in 2017 (46 so far, though that number does not include the high-profile CAR-T and gene therapies approved this year) has now topped the all-time high of NMEs approved in any year except 1996.
But the record number of approvals comes as experts, including CDER Director Janet Woodcock, have expressed reservations about tracking NME approvals like a horse race, or comparing one year's approvals to another since the agency is limited by the applications it receives.
Frank David, MD, PhD, managing director of the consulting firm Pharmagellan, explained to Focus: "Over 90% of drugs that are submitted to FDA get approved, so the NME count mainly a reflection of the number of applications - which, in turn, reflects the registration trials that were funded 2-3 years ago. With such relatively small numbers, there will always be noise - two more NMEs this year, three fewer next year, and an occasional year with many more or many fewer - but I don't think the short-term comparisons mean much."
The 46 approvals so far in 2017, compare to just 22 NMEs approved in 2016, 45 in 2015, 41 in 2014, 27 in 2013 and between 18 and 39 approvals each year dating back to 2005 (1996 holds the record with 53 NME approvals).
An FDA spokesman told Focus: "Worth noting the year is not over --- but 46 would not be a
record...there were more in 1996. The definition
of NME has not changed."
As far as terminology, the agency said it tends to use “novel” approvals as opposed to
“NME,” given the growing number of novel biologics approved that
are technically not NMEs. The agency said it focuses more on the medical value of approvals as opposed to the number since being “novel”
does not necessarily mean valuable. A report is forthcoming in early January that discusses the notable novel and non-novel drug therapies approved in 2017.
"Over the long term," David said, "It's interesting that more drugs seem to get approved per year now than a decade ago. I think one big reason for this trend relates to the therapeutic areas in which development is most active. Cancer and rare diseases have gotten much more 'hot' over that period, mainly because those are areas with accelerated and perhaps lower-risk approval pathways and sustained premium pricing - and those are also areas with typically faster and cheaper R&D (compared with, say, hypertension and depression)."
The NME count trend over the longer term also reflects what R&D is incentivized, he added.
"Today, many drug companies would gladly fund several shorter, cheaper, and less risky Phase 3 programs in indications with robust premium pricing over a single expensive, risky, do-or-die bet in a larger indication with more pricing constraints or risks - regardless of the programs' relative clinical impact - because that's the strategy that garners loyalty and capital from investors," David said. "I think that's a big reason why we get more drugs per year now, especially in cancer and rare diseases, than we did 10 years ago."
Another trend highlighted by Bruce Booth, a partner at a venture capital firm Atlas Venture, in Forbes is that since 2012, "we’ve seen a decline in mechanistic novelty. From 2012-2016, one-third to one-half of all approvals targeted novel, first-in-class mechanisms of action ... In contrast, so far in 2017, we’re running a just above half that rate: only 19% of the new drugs approved are first in class."
And the lower numbers of first-in-class approvals and higher-than-average approval numbers in 2017 may also be taken as a sign that FDA's standards for approving new drugs are slipping or down over time. Critics often point to the approvals of Sarepta's Exondys 51 (eteplirsen) and the twice-rejected Addyi (flibanserin) as prime examples of such a decline.
However, Woodcock said at a Stat News event in November that she was "irritated by this" narrative that FDA is dumbing down its standards.
David also explained why this trade-off might not be the case: "I wouldn't say that we are clearly trading quality for quantity in terms of NMEs. It's just that I honestly don't know for sure if we are or not. That's the question we need to be asking: not how many new drugs are Americans getting each year, but how much has our health improved. I don't know of a good analytic method that fairly accounts for the difference between a drug that has a modest impact on many patients and one that has a huge impact on very few, but conceptually, we should be analyzing R&D productivity with a more clinically relevant metric than just the number of approvals."
The tracking of NME approvals on an annual basis will always go on, but perhaps there will be better metrics to use, especially since so many novel treatments and generic drugs (FDA in 2017 saw another record year for total approvals, though the number of first generics approved has fluctuated from a total of 74 first generics so far in 2017, to 73 in 2016, to 90 in 2015 and 97 in 2014) are not included.
Article updated on 12/22 with comments from Frank David and the note that 1996 had the highest number of NMEs approved ever.