Andreas Persidis, CEO
Everybody agrees that the success of a drug increasingly depends on the total value it delivers. The commercial performance to date of Lundbeck’s antidepressant Brintellix is a case in point.
Having demonstrated statistically significant efficacy over placebo in study results reported in 2012, Brintellix was approved by the FDA in 2013. Brintellix’s sales are however off to a slow start; and while it managed to enter the market in the US, Brintellix (vortioxetine) has still to receive approval by the National Institute for Health and Care Excellence (NICE) in the U.K. According to the first review: “… the Committee concluded that there was no convincing evidence to show that vortioxetine was any more or less effective than other antidepressants.” It appears then that while Brintellix can still grow it’s sales this will probably take longer than expected.
The Brintellix story is one of a growing number that tell us that in order to have a fighting commercial chance, new treatments will have to convince physicians, patients and increasingly the regulators and payers who look for a clear differentiation from existing therapies. Which now begs the question:
In view of the challenges faced by Brintellix, can the traditional way of developing new therapies, namely discovering NCEs and taking them through the well known “12+ years, $1BN+” drug development process continue unchanged and as the sole development pathway available to the industry? If the relative value of a drug and hence whether it makes it on formulary lists depends on demonstrable differentiation, is the NCE development pathway the most effective use of scant resources?
Systematic Drug Repositioning (SDR) is a relatively new pathway to therapy development with its own group of proponents and skeptics. Unlike what many might think, SDR is rather complementary to NCE development; where it differs is in terms of some of the tools and the “raw materials” it uses to find solutions. Whereas NCE development takes a new compound and gathers data about that compound as it is being developed, SDR starts with compounds for which (a) more data is available and (b) the nature of that data is – to start with – richer.
Take the typical entry point of a DR candidate: Phase IIa. At that point a NCE has at best basic toxicity, animal model efficacy data and some limited human trials data. By comparison, a DR candidate has all that and, if it has entered the market, a much more comprehensive body of evidence-based data on both its benefit and risk profile.
|MoA / efficacy||Purported / limited evidence||Purported / usage evidence exists|
|Comparative data wrt various performance characteristics of SoC||No data exists||Data can be collected and compared|
|Available data refers to:||Experimental results||Experimental results, evidence based data from actual use of drug in market.|
So at the Phase IIa stage where many pipeline decisions are made, on the one hand pharmaceutical companies have a NCE with a certain amount of data and on the other a DR candidate with much more and richer data to characterize it.
Considering now the nature of the task pharmaceutical companies set themselves: it used to be the case that it was sufficient to show efficacy over placebo in the disease of interest and a justifiable toxicity profile to get approval and get listed on the formularies. Sadly for Brintellix this is no longer the case. Lundbeck has needed to show that it is more efficacious than SSRIs, has a better side-effect profile or that it achieves a more rapid onset of action compared to the current multiple weeks that SSRIs need.
So if we generalize from the Brintellix case, when pharmaceutical companies are considering what unmet needs to focus on, the spec sheet for any new therapy they may be contemplating is a nightmare of uncertainty consisting of:
- A purported MoA for the candidate at hand.
- A required risk profile (which may be a function of the risk profile of the standard of care).
- One or more features such as “a more rapid onset of action” (usually translated as a set of additional purported
MoAs that the drug will need to possess) that address whatever shortcoming(s) the competition has, and allow it to be sufficiently differentiated from that competition.
To rise to such a challenge, it is clear that you need all the help you can get – that you need as much data as you can generate to compensate for the uncertainty of the data at hand. And so when it comes to selecting between a NCE and a SDR development pathway, it is certainly not an “either-or” question. It may not even be a question of which one to use in which case. Given that we certainly cannot ignore NCE development, the question to ask is “can we afford to ignore the tools, resources and mindset of SDR?”