The FDA regulatory process is complex and rife with failures 🥇 Here’s what it takes to succeed and avoid mistakes that sink drug development programs
In our last edition of The Business of Biotech, we illuminated the FDA regulatory process. Now, let’s dive into the common mistakes that sink clinical trials and how we can avoid these pitfalls.
🥇 Striking Gold
No one in the industry will tell you that drug development is easy or that the approval process is smooth. It can take years to find out that your beloved drug candidate is a flop. However, each successive stage of clinical success “de-risks” the endeavor and makes approval more likely, increasing the valuation of the company and drug asset and bringing media attention to the development program. Biopharma M&A activity witnessed rebound in 2023, with total deal value up by 79% vs. 2022 to reach ~$152B for the full year, trend towards levels last seen in 2020 (reference). The M&A trend over the last decade has been weighted towards preclinical and Phase 1 lead drug assets. This trend has started to shift to Phase 2 and 3 assets as the industry becomes slightly more risk averse.
❗ Why Do Clinical Trials Fail?
Four out of five clinical-stage drugs fail in trials. The potential culprits are many, and some are unavoidable, but risk can be reduced by proper planning and understanding key drug development principles.
These biological factors include:
- Lack of understanding of mechanism of the new drug. We understand the precise mechanism of action of CYT-108, which is protease inhibition.
- Lack of understanding of the pathophysiology of the disease. We pioneered research into the molecular pathogenesis of osteoarthritis, and deeply understand this multi-faceted disease.
- Lack of translatability between preclinical models of disease and the actual human. The clinical and commercial success of our FDA-cleared “APIC” therapy for osteoarthritis de-risks this translatibility because we already know that the core technology works in humans.
Beyond these biologic factors, study design and practical implementation of study protocols can affect clinical trial success.
These non-biologic failures include:
- Inadequate study design (number of participants, primary and secondary endpoints). Our Phase 1 study is primarily examining safety, and we do not expect statistically significant efficacy results (although we will still measure effiacy to inform the Phase 2 study).
- Improper dose selection and time course. The proposed effective dose of CYT-108 is based on the A2M concentrations used in our APIC therapy, so we are more informed and not flying blind.
- Inappropriate efficacy metrics/endpoints. The safety and efficacy endpoints (WOMAC score) we are using are accepted as the gold standard for osteoarthritis clinical research.
- Inappropriate statistical analysis of data. We are not expecting statistical significance in the efficacy data. However, we will look for trends in the data to get a sense of the efficacy of CYT-108 in reducing cartilage damage.
🗝️ Keys To Success
Regulatory success can be optimized by paying extra attention to the following:
- Exclusion and inclusion patient recruitment criteria. We very carefully selected our inclusion/exclusion criteria to only recruit healthy patients with mild-to-moderate osteoarthritis of the knee.
- Number of participants to make the study highly powered (so that statistical significance can be determined). We are not concerned with statistical power in our Phase 1 study.
- Optimal dosing schedule based upon the pharmacokinetics (the way that the drug metabolizes and clears the drug from the body). Based on our preclinical research, we know that CYT-108 is not able to enter the bloodstream in meaningful concentrations due to the large size of the molecule.
- Possible food effects and drug interactions. Our inclusion/exclusion criteria prohibit the use of other therapies for osteoarthritis during the Phase 1 study.
- Selecting the appropriate efficacy measures/endpoints. We are using the gold standard for osteoarthritis research.
- The best endpoints translate directly to clinical benefit (For example, the rate of tumor growth is a great measurement to determine the efficacy of an anti-tumor drug in curbing cancer progression). We are using the gold standard for osteoarthritis research.
- Biomarkers can be used to quickly measure the effects of a drug (For example, a tumor growth biomarker circulating in the blood could be used to determine cancer progression with simple blood analysis). We are going to perform an assay to measure cartilage degradation from patient blood samples. This will give us a highly quantitative insight into CYT-108’s ability to stop cartilage damage.
In our next edition of 🧑💼 The Business of Biotech, our CEO, Joey Bose, will give you a peek into his day-to-day of running a biotechnology research and development company.
Ready to become a shareholder? Visit invest.cytonics.com.
This communication may contain forward-looking statements and information relating to, among other things, the company, its business plan and strategy, and its industry. These statements reflect management’s current views with respect to future events based information currently available and are subject to risks and uncertainties that could cause the company’s actual results to differ materially. Investors are cautioned not to place undue reliance on these forward-looking statements as they contain hypothetical illustrations of mathematical principles, are meant for illustrative purposes, and they do not represent guarantees of future results, levels of activity, performance, or achievements, all of which cannot be made. Moreover, no person nor any other person or entity assumes responsibility for the accuracy and completeness of forward-looking statements, and is under no duty to update any such statements to conform them to actual results.
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