Innovation through risk is vital to our industry. By following the well-trodden path, for example by pursuing “me too” therapies, you can minimize risk of technical failure. However, in doing this, you may miss the answer to a question that could revolutionize a treatment approach, inhibit an “undruggable” pathway, reveal a novel modality or miss out on a new technology that brings us one step closer to achieving a cure or preventing a serious disease.
Historically, clinical development has followed a sequential path from Phase 1 through Phase 3 and beyond, with programs primarily designed to demonstrate “proof of concept” and confirm efficacy and safety. In this paradigm, studies are designed, executed and the results analyzed before moving on to the next stages of development. This approach allows for an orderly governance process with incremental investment decisions, based on data characterizing the emerging product profile. Given the high cost and risk of attrition at every stage, this sort of incremental approach has distinct advantages.
Breakthrough therapies, however, do not tend to follow this sequential development path. The lines between stages blur and studies may be modified based on interim rather than final data. Dramatic efficacy signals in ongoing studies may trigger attempts to expand or accelerate programs. What may start as a Phase 1/2 study may be evaluated and expanded to serve as the basis for a regulatory approval. Changes like this in an ongoing development program are exciting and offer the opportunity to deliver value to patients much faster. However, they challenge the deep-rooted governance and resourcing models in pharmaceutical companies and often require us to “innovate through ambiguity.”
The need to rapidly pivot resources to potential breakthrough programs is often easier said than done. Budget and internal resources may be fully allocated to other programs. Initiating a new clinical study or amending an ongoing one to support regulatory approval may require time and additional quality measures. It is also common to have issues with availability of investigational products at an early development stage, as they are often prepared to a different quality standard and manufacturing may not have yet been scaled to support larger studies, let alone commercialization. Depending on the availability of material or cycle time to manufacture the new product, pivotal trials and approvals may be delayed.
Delivering genuine innovations at this level, safely and efficiently, requires an organization-wide mindset that accepts and embraces risk, learns from failures and unlocks the power of diverse skills. Yet, as an industry, how do we instill this mindset while ensuring it is managed within frameworks that can help minimize these risks? At Astellas, a key focus is to shift investment and resources to potential breakthrough technologies such as gene and cell therapies and to apply the latest principles of risk-based quality management to prospectively identify risks and implement controls to mitigate those risks throughout the product lifecycle.
As new, preventative treatments and cures are discovered, the role of biopharmaceutical organizations will inevitably need to evolve and confront new issues and opportunities. As more diseases cease to be life-threatening or life-ending, age and longevity will rise, and with that, the need to help with other conditions of aging—both health and economic related. Our industry may shift from primarily being a developer and supplier of treatments, to a partner in helping health systems identify new needs and supporting them in the design and delivery of the sustainable innovations of the future.
Bernhardt G.Zeiher, M.D., F.C.C.P., F.A.C.P.
Chief Medical Officer, Astellas Pharma Inc.