In amongst the near euphoric – and to an extent justified - response to the recent rise in the SP and the seemingly endless optimism surrounding the future potential for BOT, there is one significant challenge in the near term – and that is to succeed in meeting the primary endpoints of the BTX1503 Phase 2 acne trial.
Put simply - Phase 2 trials are the most significant hurdle for any new pharmaceutical treatment trying to get through the regulatory process – with lower success rates than any other Phase.
IQVIA – global leaders in healthcare and related information recently published a report titled “The Changing Landscape of Research and Development” which included a detailed analysis of the success rates across different clinical trial phases from 2008 to 2018.
Significant highlights from the report for me are that:
- The composite success rate of clinical development stages from Phase I trials to regulatory submission fell to 11.4% in 2018 – highlighting that for every 10 new products that go into Phase 1 trials – only 1 will achieve regulatory submission
- The average success rates for Phase 2 trials is less than 40% - so fewer than 4 in 10 drugs succeed in achieving the primary endpoints and go through to Phase 3
So –in the absence of any other information – the likelihood of BTX1503 achieving regulatory success is around 1 in 10 – and we only have around a 4 in 10 chance if getting through Phase 2. And by “any other information” I don’t mean individual ‘before and after’ images and the odd TV/PR fluff piece.
But – you might be asking – hasn’t management given us solid clues as to likely success? After all – in the investor slide decks they describe BTX1503 efficacy compared to leading acne products very positively “BTX 1503: acne – outperforms leading acne products”
And this is where it gets interesting in terms of the potential market response to any Phase 2 trial results which typically compare active agents with placebo/vehicle.
In the current trial BTX1503 is being compared to placebo/vehicle – and Phase I trial results suggest it has significant potential – with a 45-47% reduction in inflammatory lesions and 22% reduction in non-inflammatory lesions at day 35 (sourced from the Botanix investor presentation).
While Botanix put a positive slant on this – it isn’t difficult to find data that suggests the current treatments are also relatively effective – and perhaps even more so than BOT in reducing non-inflammatory lesions
A clinical review of the data in support of EpiDuo prepared for / by the FDA shows data on EpiDuo reducing inflammatory lesion count by 52% compared to placebo / vehicle of 32% - a larger reduction than for BTX1503 in the Phase 1 trial
[Source: www fda gov/media/75583/download]
Similarly, Epiduo is shown to reduce non-inflammatory lesion count by 45.9% compared to placebo reduction of 27.8%
For the sake of discussion – let’s assume BTX1503 achieves very similar results in Phase 2 as was achieved in Phase 1.
The first question is – how does this compare with placebo?
While BTX1503 may be superior – placebo response rates in acne trials are remarkably positive – a point mentioned in the investor presentation (“Studies showed large placebo / vehicle effect – i.e. at 12 weeks Aczone reduced inflammatory lesions by 54% while vehicle achieved 48% reduction. ”) – and reinforced by the placebo response in the EpiDuo trial referenced above.
Furthermore, investors who are not experienced in interpreting trial data may see the ‘statistically’ significant result as less impressive than the implied clinical significance or competitor comparison.
Without a clear gap (in the eyes of the market) between BTX1503 and placebo – there may be some potential for misinterpretation of the significance of the result – and particularly if the market attempts to compare efficacy across different trials. While such comparisons are unscientific – they are inevitable.
IMO the market is sometimes somewhat challenged in its ability to interpret trial results. A good example is the market response to Paradigm’s unequivocally positive result with iPPS for osteoarthritis. A common parameter used to measure effectiveness in osteoarthritis trials is the percentage of patients who achieved a 50% or more reduction in pain. While PPS achieved this – it was interesting (and somewhat concerning) to see the muted and delayed market response – and comments on HC forums along the lines of “it only works for half the patients” – which is NOT what this suggests.
My personal view of the likely outcome of the acne trial is an optimistic one – with an expectation the primary endpoints will be met – particularly as BOT is only being compared to placebo rather than competitors.
There is also an engaging ‘mode of action’ story to be told – with the combined anti-inflammatory and antibacterial action which would be a logical approach for the treatment of acne.
However, I remain less than optimistic about how the market may respond unless there is an obviously significant improvement over placebo – and also a difference that at least alludes to likely improvement in efficacy compared to competing treatments.
And I would be particularly concerned if we were to not see detailed results from the recent BTX1801 Phase 1 psoriasis trial and then see an attempt to ‘spin’ a less than impressively positive Phase 2 result.
It has been a wild ride recently– and the long, drawn out wait for anyone holding from 7c or 8c upwards has made the recent rapid re-rating of the SP particularly satisfying.
Let’s hope for a solid Phase 2 result to keep the excitement and momentum – else we’re in for a particularly turbulent time.
All IMO only / please DYOR / but GLTAH
(20min delay)