As biotech experts, risk taking is part of our business model. Without scientific and business risk, inventions would not occur and businesses would not grow. How do we know we are taking appropriate risks at the right time? How do we know we are using agile drug development strategies by tracking, understanding, and mitigating risk as our therapy proceeds from the bench through clinical trials and product launch?
These questions get to the core of being a Drug Hunter. As a neuroscientist who started at the bench and became an R&D business strategy, compliance, and risk expert, I know these are issues to be continuously refined over one’s career.
Parts of these questions, especially those surrounding early drug development, have been discussed in articles available as resources at Drug Hunter such as, “Don’t Work on Things That Don’t Work” and “What is a Drug Hunter”.
Linking early-stage drug discovery and development with the clinical and launch stages and viewing them as a continuous whole, dependent on one another, is key to maximizing success.
While there are many factors to the post-launch success of a therapy, this article will focus on 3 key issues that are linked:
- End-to-End Clinical Risk to Benefit
- Anticipating Future Competitors and Understanding Current Ones
- Market Fit
End-to-End Clinical Risk to Benefit
Each therapy is developed and tested at various stages to be effective and safe (for example, understanding adverse effects). We use internal and external data on anticipated or known clinical impact of the therapy or similar therapies, along with business analysis and projections to make risk-based decisions considering numerous factors, such as balancing cost, time, and regulatory requirements. Yet, we understand that no matter how much effort is devoted to these processes, there are unknowns and limitations for each therapy that we cannot control. What we can control is the process of anticipating and understanding the clinical risk to benefit profile using a strategic, risk-based approach from the earliest stages.
Many readers have seen cases such as this story based on my experiences. A biotech company developed an innovative new drug to treat hematologic cancer. The drug was approved in record time under an accelerated approval and quickly generated more than $6 million in revenue. A year later, increasing cardiovascular adverse effects pushed the FDA and the company to agree to halt sales while they further studied the issue.
To effectively practice risk-based, agile drug hunting, we come together collaboratively using a Lessons Learned approach, to examine such situations and find potential ways risk could be anticipated earlier, mitigated, or managed to reduce the later stage impact to patients and the firm. At the same time, we need to understand what opportunities we may be giving up by mitigating potential risk. For example, delaying time to market, possibly having competitors beat the firm to market, and pushing anticipated revenue out further.
Anticipating Future Competitors and Understanding Current Ones
As part of the process of making a business decision around the developing therapy, we collect data and information not only about our therapy but about current and anticipated similar therapies. Included in these analyses is an understanding of our firm’s therapeutic risk to benefit profile obtained through the process discussed above.
If the risk to benefit profile is insufficient at any stage, therapy development can be terminated or altered using the risk-based agile approach to development.
It is important to keep in mind that competitors are not only other similar therapies but could be a device in place of a drug or vice versa or could be an inappropriate therapy, a home remedy or even no therapy at all if patients and physicians do not see a need. As we observed with COVID-19, some individuals chose an approved mRNA or adenovirus-based vaccine or a therapy like remdesivir, which was granted emergency approval, while others chose not to take any preventative or treating therapy, and still others chose unapproved therapies like ivermectin.
This understanding changes as we learn more about our therapy during development, which necessitates an agile process. For example, once a product receives health authority approval to be marketed, the advantages over competitor products or specific use cases in terms of efficacy and safety may be clearer. Using the risk-based, agile approach, communications and competitor comparisons can then be updated for strategic, accurate and appropriate clinical communication.
While market size is one consideration in building a business case for pursuing drug development, following the deterioration of the blockbuster drug business model, companies have found new models that accommodate smaller size markets, for example in a rare disease where only a few thousand people may need the therapy.
Business analysis for market fit includes asking if the potential therapy solves a health problem for enough people in a meaningful way that justifies a payment model that covers the expenses, opportunity costs, and risks of funding the research. One example is hepatitis C virus (HCV) treatments. While the total market size is substantial, about $4 billion in the United States, the size of the market is declining as awareness, prevention and early treatment increases. At the same time, a number of new products, for example, Sovaldi, Harvoni, Mavyret and others, have recently become available, many with reduced adverse effects and/or shorter treatment times compared with older treatments, such as interferon. The cost of developing these therapies is high. On the other hand, overall medical costs for people with HCV is expected to reach $9 billion in the next 2 years. Increased competition is driving down cost of therapy, but insurers and patients may still consider short-term costs high. Balancing all these factors go into decisions by corporations and patients on investments, treatments and what to pay for.
Market fit can change over time at a firm. Many companies conduct business analysis to identify and select therapeutic areas where they have built up excellence and fit with their current business model. In cases where a potential product solves patient problems, but the therapeutic target or market size is no longer a fit for the organization, could the firm out-license it to another where the market size or therapeutic area is a better fit? One example of out-licensing’s effectiveness at finding a fit for therapies is Cytopia, which we highlighted previously.
Even the National Institute of Health has recognized the importance of “Fast-Fail”. It lowers costs and increases chances of significant success. At the same time, some people could argue that important products may be discarded too early and with modest extra effort they could be important therapies. Losing such important therapies is a risk. After all, key therapies were identified while searching for something else or due to misunderstanding and mistakes in early research: aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. These serendipitous therapies show us that drug discovery is both art and science.
We are strongest when we combine art with science. Science tells us it is never too early to assess our three key factors for product success because this enables resources to be directed to the best candidates to move forward toward helping patients. It is also necessary to periodically re-assess and ask, “Are these factors still true? Are we still on the right path?” Or even, “Have we missed a miracle?” This risk-based, agile development is what distinguishes outstanding drug hunting. Happy Hunting!
About Candice M. Hughes
A serial entrepreneur and innovation expert with biopharma compliance expertise, Dr. Hughes is known for turnarounds and startup launches. At Hughes BioPharma, founded in 2005, Dr. Hughes restructures R&D operations processes and compliance at global biopharmas, having worked with 50% of the largest 25 global pharmas and smaller biotechs. An early digital health startup founder, she also founded a gold standard healthcare division at a venture capital backed media firm. Living Loud Living Long for 50up women digital well-living community and media startup was founded by Dr. Hughes in 2021.
Dr. Hughes is a Board of Director member and Deputy Global Chair (Affinity Group) at the Healthcare Business Women’s Association. She was a Board of Directors Member and co-owner focused on Corporate Governance and Compliance at a mid-size for-profit private energy firm.
She received her PhD in Neurobiology at Boston University School of Medicine and MBA with Beta Gamma Sigma honors at Kelley School of Business, Indiana University. She conducted postdoctoral work on Alzheimer’s Disease at University of Rochester School of Medicine. She provided industry input as a Delegate at the White House Working Families Business Schools Convening and participant at Milken Institute Future of Health Summit. She is a sought after startup Advisor, Board Member, speaker and published author.