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Fail Early, Fail Fast - And Increase Likelihood-of-Approval

What is this saying “Fail Early, Fail Fast” all about? Is there any merit to it and how is this changing the game for all pharmaceutical drug development companies? Here we will give our thoughts and opinions into how this really carries over to the real world and how it affects the industry.


While no one plans to fail. Big Pharma companies have adopted this “Fail Early, Fail Fast” mentality that plays largely into the overall strategy and trends of the Pharmaceutical industry.

Clearly people don’t strive for failure, but they are doing everything they Fail Fast Fail Early.pngcan to identify a failure from a success as quickly as possible. By failing early, and failing fast, you are saving money. It’s no secret that clinical trials not only soak up time and energy but also rack up quite the bill. The big push for Precision Medicine is forcing pharmaceutical companies to serve smaller patient populations, potentially putting “blockbuster drugs” at risk. Creating drugs from a smaller patient population requires the cost and length of trials to be reduced in order to maintain a line of profitability. Thus, reinforcing the “Fail Early, Fail Fast” importance in overall profit.

 

What's the role of Biomarker's in “Fail Early, Fail Fast” (And Fail Cheap)?

Simply put, biomarkers are crucial to depicting failure or success. Biotechnology Innovation Organization (BIO) partnered with Amplion to publish a report demonstrating how the use of biomarkers in trials drastically increases the Likelihood of Approval (8.4% → 25.9%). Biomarker presence and use in clinical trials is crucial not only to success, but also to identifying the failures as early as possible.

Biomarkers allow companies to identify a drug’s effect early in the treatment cycle. They are the future of drug development and will be integral in the overall process of verifying effectiveness and likelihood of approvals.

So, how are biomarkers crucial to the "fail early, fail fast" goal? Biomarkers are used in the early stages of drug development to determine the effectiveness of a new compound or a new drug indication. Assays measuring surrogate biomarkers are a key part of the pre-clinical drug development process. However, biomarkers can still be slow and expensive to validate, negating much of the "fail cheap" goal. This is why you hear much about the single surrogate biomarker to determine the promise of a new compound or new drug indication. Identifying, validating and measuring one biomarker is cheaper than many.

However, as we discover more about biomarker signatures it is unrealistic to think that the single biomarker is the right approach. That means that we are back to increased costs to evaluate multiple biomarkers for a drug program, but also the althorithmic interplay of the biomarkers.

So, there is still a battle to be had in the cost of validating biomarkers for a drug program.

Over the next few years the problem of valid biomarker signatures for determining a new compound's efficacy will be front and center.  The converse is quickly determining the lack of efficacy for new drug programs.  At Amplion, offering access to biomarkers and their evidences is our primary business.  While we do that with advanced AI techniques, at the end of the day we are providing expedited access to the information needed to make decisions as early as possible in the drug program life cycle.

 

How It Affects The Industry

 

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Fig 1a

Image Source: Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN. Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat Rev Drug Discov. 2014 Jun;13(6):419-31. doi: 10.1038/nrd4309. Review. PubMed PMID: 24833294.

AstraZeneca published a definitive analysis of their pipeline from 2005-2010 in 2014.  That analysis showed a significant and costly fall off in percentage of trials moving successfully from phase II and from phase III as compared to industry averages.  The study elaborates, "Of the projects analysed, 94 closed during the period assessed; 33 closed before clinical testing and a further 61 closed during clinical testing. The remaining projects were still active at the time of this review."

This is precisely why pharmaceutical companies, even the largest, must adopt a "fail fast, fail early" strategy. The cost of drug program failures in the clinic, especially late phase, is very high.

Recent data represents an overall decrease in Drug Approval Rates throughout the industry. As we mentioned in the intro, this does not seem to match with the trend toward precision medicines.  If, as an industry, we are effectively building a precision medicine portfolio, you'd expect this trend to be reversed.  At Amplion we believe that this trend will change to be more in line with expectations, it will take time, innovation and real work.

Diagnostic companies will need to come up with assays that target specific sub-group -omics attributes of patients.  Pharmaceutical companies will need to target drugs at similar attributes or attributes on the relevant pathways.  And the economics for both diagnostic and pharmaceutical companies will need to support smaller patient populations. 

Focusing on these goals will not only improve LOA, but it will allow hyper-early killing of loser drug programs that don't meet a higher standard of efficacy provided by diagnostic and drug discovery techniques aligned with the "fail early, fail fast" ethos.

On the other hand, as trials fail faster due to new technology and research, companies are pushing more and more trials into the pipeline, ultimately leading to a decrease in approval rates. Maybe not because the FDA is more strict or trials are harder to validate, but because the technology allows for us to actually push for quicker identification of the drug’s effect. In order to truly embody the “Fail Early, Fail Fast” mentality and actually Fail Cheap, you must implement this strategy early on in your drug discovery process. Ideally, a drug should never even be looked at by the FDA if it has not passed this initial “screening”. The importance of recognizing a failure in the pre-clinical research phase will allow you to save time, money, and push new drugs into the pipeline faster than ever before.

With advances in the pharmaceutical and diagnostics world, earlier detection of failures will allow for a higher quality of trials to be pushed into the clinical pipeline and thus increased approval rates.

 

Example claiming the adoption of Fail Early, Fail Fast in Pharma Companies.

 

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Topics: Insider, Biomarkers in Clinical Trials, Amplion, precision medicine, fda regulation

   

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