Transforming oncology clinical development: A new path to innovation

By Keith Morris, RPh, MBA, Capgemini Consulting, & Carmen Allegra, MD, Novo Oncology Associates

Given the staggering statistics on cancer rates, there is a renewed emphasis on cancer research and development—with more than 1,000 oncology compounds currently in development and a significant share of the overall industry R&D spend dedicated to oncology. Historically, the rewards have been big. Blockbuster drugs Avastin, Rituxan, Herceptin and at least 7 others each generate more than $1 billion in annual global sales. However, the development risks are substantial and growing.

It is clear that the more we understand the scientific basis of cancer, the more complex it becomes. Two patients with a similar diagnosis and given the same treatment may show very different responses and outcomes. A cancer diagnosis – be it lung, breast, colorectal or others – requires an understanding of how that specific disease originates and how it progresses and spreads in the human body.

With oncology drug development, the risks continue to increase and costs are becoming unmanageable. The trend toward targeted therapies and companion diagnostic tests means that the representative clinical trial patients will be even more challenging to identify as only a fraction meet the traditional inclusion/exclusion criteria-increasing development costs, slowing time-to-market, and potentially leading to a limited label.

Acceptable oncology clinical trial endpoints appear to be a moving target, often influenced by the various positions taken by regulatory authorities, medical academics, and patient advocacy organizations. This uncertainty adds a considerable amount of risk and instills a defensive (and costly) posture by the innovator company. Tumor response, progression-free survival, and overall survival are among the intermediate and final endpoints that must be measured, but often have a different weighting among regulatory authorities.

The recent FDA interest in and emergence of combination therapies during clinical trials, similar to the "cocktails" use to treat HIV, also leads to more complex trials, requiring multiple companies to work together in a unique situation. A more active, educated, and engaged cancer-patient population expects more manageable side effects with cancer treatments of the future.

To complicate matters even further, financial pressures related to private and public payors are challenging reimbursement levels for cancer drugs and treatments. Companies must evaluate the payor perspective and how they define the value of oncology drugs.

The industry is facing a genuine dilemma. As costs are skyrocketing and reimbursement challenges occur, are clinical development programs designed to deliver incremental improvement in cancer care a thing of the past?

Transformation of oncology clinical development

As pharmaceutical and biotechnology companies search for a cure, the central issue is: how should oncology clinical development be transformed to better manage the risks?

The right treatment to the right patient

The use of biomarkers to match the most effective treatment with each individual patient will remain the focus in the industry. This despite the reality that an initial, smaller patient population puts at risk recovering the development costs. The price commanded for a drug that will be more effective in these smaller patient populations combined with additional product lifecycle opportunities boosts the revenue potential to justify the investment.

Early decisions on product strategy

Considering the significant risks and associated costs of oncology clinical development, key product strategy and go / no-go decisions need to be made early in development. This requires a deep understanding of a compound's mechanism of action and of future standards of cancer care. It also means making critical product positioning decisions early (such as first- or second-line, stand-alone or combination) based on scientific and commercial insights. Access, reimbursement and other payor issues are also key factors. With major uncertainties, parallel development of agents within organ-defined patient populations (colon, breast, lung, prostate) may be required to maximize the scope of eligibility for individual patients. With the advantage of more precise targeting of specific agents for individual patients, this approach may help minimize clinical trials costs and greatly accelerate the development timeline for these agents.

Redefined endpoints

To accelerate speed-to-market, intermediate endpoints that represent an accurate reflection of global clinical benefit and are acceptable to the regulatory agencies are urgently needed. Developing such early metrics is challenging in part because of the complexities and variability of the patient care pathways. Further complexity results from multiple interventions that may occur during the lifetime of a given patient's care, as each intervention used may confound the "gold standard" endpoint of survival. Identification of new, valid short-term endpoints that are widely accepted across the industry by investigators, payors and regulators remains a critical yet unmet need.

An eye on the competition

Understanding competitors' pipelines and critical areas of clinical need are important in developing a clear and certain direction and timeline for product approval. Successful trials will change the standard of care and set a higher bar for efficacy and tolerability.

Speed to market

Once a strategy is set, patient enrollment, trials execution, data analysis and dossier preparation must be managed as a process to be continually optimized. It requires early involvement of the regulators, and in some situations payors, to prepare for rapid decisions and acceptable data points for approval and reimbursement.

Collaboration for better cancer care

The upcoming wave of product innovation in oncology and the progress towards personalized medicine holds an exciting promise-a world with improved cancer care that far exceeds the tedious, incremental progress that has beset cancer developments. Progressing rapidly towards significantly better outcomes will require collaboration between patient groups, pharmaceutical companies, regulators, investigators and payors to maintain a reasonable balance between accelerating safe access to innovative care and managing the cost of care to a level within societal tolerance.

Capgemini Consulting is among the world's leading advisors to the pharmaceutical and biotechnology industries, offering management consulting services to drive strategy formulation and accelerate the transformation of life sciences companies. Through its alliance with Novo Oncology Associates (NOA), Capgemini Consulting provides its clients with actionable, specific recommendations and implementation support to enable a high degree of success within the evolving global oncology market.