red vial

We are standing at a tipping point. If the industry steers the R&D rudder in the right direction, it stands to have a drug development process that can get drugs to market at a much faster rate. However, steering towards that vision is riddled with challenges. As mentioned in the first installment of this three-part blog series around the theme of our white paper, Breaking the Constraints of the Current Development Paradigm, the classic drug development paradigm still persists.

This classic paradigm is outdated and in need of transformation, especially given the rising costs of drug development. The pressure on biopharma has expanded from merely requiring regulatory approval and market authorization, to include the necessity to incorporate reimbursement concerns very early on. Approval of drugs does not guarantee reimbursement, and this is crippling the profitability of many companies.

Moving towards that vision

Biopharma companies committed to delivering innovation have struggled to maintain profitability. The situation has pushed them to identify and leverage emerging opportunities for smarter drug development strategies that enable earlier launches.

These companies have started to look at therapy areas where there is high unmet need, a relatively less competitive environment, and potentially reduced regulatory risk aversion – essentially where there are better prospects for profitability and improved patient care.

Now the focus is on specialty drugs for life-threatening conditions and rare diseases. There are an estimated 7000 rare diseases impacting people across the globe – a number that is expected to increase due in part to advancements in health diagnostics and the ability to identify the specific mechanisms of disease.

Drugs for orphan diseases and specialty medications can be life-changing for patients who suffer from rare and life limiting illnesses. With these conditions, time is of the essence. Unfortunately, the classical drug development paradigm is lengthy and so this is compelling biopharma companies to reassess how they can bring treatments to patients earlier.

The new reality facing drug development

We are getting closer to the vision of improved R&D. By designing and adopting more sustainable R&D models, a new reality has begun where much-needed drugs are slowly, yet increasingly, reaching patients in shorter periods of time.

Advanced technology can now make use of ‘big data’ to enable more effective ways to identify true patient populations, model disease progression and identify relevant biomarkers for responder selection or as surrogate endpoints, which are essential mechanisms if drug developers are to produce robust evidence of proof of concept (PoC) early.

Use of genomic analytics and access to electronic medical records (EMRs) and patient registries enable relatively seamless methods for patient profiling, identification and recruitment, which can improve patient retention during the course of trials and expedite the overall journey towards approval. Furthermore, biopharma organizations are technologically aligned to make all of this happen.

Even regulators are onboard in making the new R&D model a reality so that innovative medications are available to patients faster. The Food and Drug Administration (FDA) utilizes special criteria to give orphan drugs or rare disease drugs fast track, breakthrough or priority review designation, and to grant accelerated approval where possible. The European Medicines Agency (EMA) have adaptive pathways, accelerated assessment, conditional market access and the PRIority MEdicines (PRIME) pathway, which encourage early interaction between developers and regulators to optimize development plans, and accelerate evaluation and launch of medications to bring innovative medications to patients faster.

Conditional approval

Supporting early dialogue between sponsors and regulators proves to be fundamental if we want to pre-plan the kind of evidence we will generate and how we will generate it. Part of the new reality of drug development is obtaining conditional approval, for new treatments based on robust surrogate endpoints and PoC. The decision is conditional on sponsor commitment to complete confirmatory studies and very close post-launch monitoring to validate the drug’s value in a real-world setting.

Figure 1: Early conditional approval in a restricted population with active surveillance post-launch

Regular R&D path

Figure 1 shows how drug development can become more adaptive and scenario-driven. The normal pre-clinical R&D pathway is taken, however, after PoC is achieved, drug developers can test the drug in more realistic settings (pragmatic trials) to document the maturing risk-benefit profile as well as gather real-world evidence (RWE), which is proving more and more valuable during reimbursement assessments. This accelerated pathway evaluates a drug’s effectiveness, rather than its efficacy. It is an opportunity to significantly reduce cycle times, and will soon be the new normal for specialty and orphan drugs.