How can I mitigate my risk of late-stage clinical failure?
If you need a car for a long road trip, the smart thing to do is to consider your options carefully and choose a vehicle that’s going to be reliable. As you decide, you may have various considerations that will impact your decision—how many people are going on your trip, budget, environmental impact, where you aim to end up. And you may be spoiled for choice; there are a lot of dealerships, makes, models, colors, and sizes to choose from. But you’re likely going to weigh your options carefully and decide what’s most important to you before you make a decision.
1. Collect high-quality data to make informed, confident go/no go decisions for moving your drug candidate forward
When it comes to planning studies for your drug’s preclinical development, even more due diligence is required because the stakes could be huge. You can’t just pull into another dealership and drive out with a new molecule. Data quality, expertise of whoever is conducting the study, and confidence in interpretation of results should be at the top of the list for considerations for safety studies because inaccuracies or missed red flags early in development could result in big problems or even failure down the road.
2. Design studies carefully; a cut corner or small oversight could lead to a big problem later in development.
Pharmacokinetics and defensible risk assessment can make or break a drug’s chances of success in the clinic. When it comes to avoiding technical and translational pitfalls, preclinical results pointing to possible safety concerns, such as drug-drug interactions (DDI) or toxicity, should be properly investigated through experiments yielding sound, trustworthy data. To responsibly evaluate risk factors, proper study design of nonclinical studies is of critical importance. This requires careful consideration of early in vitro data and results from other preclinical testing to tailor study designs to appropriately answer questions or build a strong data package for regulatory submission.
Inadequate ADME properties can be devastating to otherwise good drug activity.1
When choosing a CRO partner or performing your own in-house studies, make sure you work with someone with enough experience to respond appropriately to unexpected issues in the planning process, who can offer flexibility in assay design to fit specific needs of your molecule and offer a consultative approach to results delivery or submission package advice.
When you need IND-enabling studies exploring your compound’s DDI potential or pharmacokinetic properties, we’ve got you covered.
3. Consider drug-drug interaction (DDI) potential and prioritize pharmacokinetic profile data early in the development pipeline
Regulatory authorities worldwide have continuously underlined the importance of early, thorough investigation of safety-related properties including pharmacokinetics and DDI potential in publications and updated guidance documents to encourage diligent practices in preparation for submission to clinical phases. Preclinical data can be used to maximize patient safety and prevent patients from being unnecessarily excluded from participation in a trial. Early studies in relevant, predictive experimental models to explore drug metabolism, drug transport, enzyme inhibition and induction, metabolite formation, and other factors, each can contribute valuable insight to the overall risk considerations of a drug, helping drug developers make better decisions and anticipate clinical results.
4. Develop a plan to properly investigate unexpected results along the way
Your drug candidate is unique. Throughout the discovery and development process, you’re going to learn a lot about the ways your compound interacts with various proteins and all the interrelated pieces involved in its overall disposition. Anticipating roadblocks can be difficult, but knowing where to turn if you do encounter one is not. Coming up against unexpected issues in development or clinical phase can kill a compound, but in some cases it can be an opportunity for innovative problem-solving.
Our pool of in-house and external experts can help you when you find yourself facing ADME and DDI-related challenges. Gap analysis, IND-submission review, synthesis of in vitro data, response to regulatory questions, and other services are all in our wheelhouse. Our hand-picked consultants have extensive experience in the field and have seen and helped navigate many obstacles for drug developers. Get in contact with a contract service specialist to see if we can find a solution together by matching you with one of our very best.
Failure in late-stage drug development or attrition during clinical trials is always a risk for drug developers and some circumstances can’t be avoided, but some can. Preparing your team to be proactive, value quality results to base decisions on, and respond well to challenges along the way will help you navigate your drug’s development pipeline and maximize chances of a successful outcome, bringing a novel therapeutic agent to the patients who need it.
- Kenakin, Terry. “Pharmacokinetics I.” Pharmacology in Drug Discovery and Development, Second ed., Academic Press, 2016, pp. 157–191.