Following on from yesterday’s post about FDA approvals, here’s another short Nature Reviews Drug Discovery synopsis, this time on Phase III drug submissions and failures trends between 2007 and 2010.
This caught my eye:
“The Centre for Medicines Research International has noted that the average for the combined success rate at Phase III and submission has fallen to ~50% in recent years.”
Ouch. Bold highlight mine.
The overall picture looks like this, based on n=83 submission failures:
I was astonished to see that oncology contributes over a quarter of the filings, but much less surprised that lack of efficacy was the reason of the failure:
“Of the drugs that failed to show an improvement in efficacy as an add-on therapy, 58% were anticancer drugs, and of those that failed to show an improvement in efficacy versus placebo, 33% were nervous system drugs.”
The author suggested that perhaps the challenging environment has led to unwise or hasty filings:
“… but is perhaps also a result of the pressure on companies to replenish pipelines with drugs that have high potential for approval and reimbursement, particularly in a period during which patent expiries for major products are threatening future revenues.
Owing to this urgency, it seems that companies have progressed drugs into Phase III trials even though they only displayed marginal statistically significant efficacy in Phase II proof-of-concept studies; consequently, these drugs carry a greater than average risk of failure.”
Sometimes that may well be true, but quite frankly, cancer trials are a bit of a crapshoot at the best of times so I’m not sure I agree with the sweeping perspective.
Promising phase II data can often lead to spectacular and unexpected phase III flops as sanofi-aventis discovered with their PARP inhibitor, iniparib, in triple negative breast cancer only last week. The phase II data was hardly marginal and was worthy of publication in the New England Journal of Medicine.
In the long run though, we learn more from failures than successes, so that others following in the wake can improve on the trial design and combination therapies used. Still, that’s not much comfort for those who blazed the path initially.
Arrowsmith, J. (2011). Trial watch: Phase III and submission failures: 2007–2010 Nature Reviews Drug Discovery, 10 (2), 87-87 DOI: 10.1038/nrd3375