Project Optimus: How to Prepare for Success

For some time, developers of cancer drugs have known about “Project Optimus” and new expectations for dose optimization are coming their way Food and Drug Administration’s (FDA) Oncology Competence Center for Oncology Drugs.

While the FDA has yet to release the details of Projects Optimus’ guidelines, there’s no reason for oncology drug developers to panic or delay action.[1] Drug developers can and should prepare wisely by planning what they can reasonably foresee.

Prepare for a situation with “predictable unknowns‘ is similar to preparing for a hurricane. Like putting together a supply package for your hurricane preparedness plan, now you want to get everything you need on hand. They don’t want to wait for the hurricane to come.

Ask basic questions
Oncology drug developers must first ask basic questions: Are we collecting enough data from clinical trials to make decisions?? Do we have the right experts on board? Are we ready from a modeling standpoint? How much will our preparations cost and are we planning our finances accordingly? Will we have enough medicine? Drug developers also need to consider whether they allow enough time for their preparations and for effective communication with the FDA.

Although each company’s situation, molecules, pipeline and approach will be different, gathering data will be the critical first step for all. This should be based on a gap analysis of the developer’s available data, from existing clinical data in current study plans to non-clinical pharmacological data. This allows any company to assess whether what is currently available provides enough input to determine optimal dosages, and if not, identify data it needs to make decisions.

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understanding
Developers should review data on all available doses from a pharmacokinetic/pharmacodynamic, safety and efficacy perspective.[2] Ask how the human data agrees with what has been understood in non-clinical studies. Also, look at the future state: ask if the data collected is relevant to decision-making, or if additional data is needed to assess or support an optimized dose. Collecting additional data can be done either by adjusting ongoing protocols or by planning additional studies.

Once drug developers are confident they have made arrangements to collect enough data, they can plan next steps. You must ensure that there is adequate time and resources to support the analyzes that the FDA will seek when submitting dose justifications. Most companies are unable to support complex modeling exercises internally. they may lean towards a simpler approach using observed data, which may be valid but limiting. Others invest in external providers. Whichever approach is more appropriate, developers must ensure they have identified the experts for the analysis required and that the data is in the right format for easy transfer and analysis.

Developers must also plan when to seek agency approval or dose feedback and identify what analytics are required for those interactions. Depending on the meeting type, FDA feedback may take up to 75 days after the meeting request is submitted; waiting for this feedback may delay the next phase of development; Businesses could lose time and money if they don’t plan for these interactions.

Robust manufacturing process
Another consideration that many may overlook is ensuring the production method is sturdy enough to support additional investigations of dose in early drug development. I recently had the example of a drug developer who only had enough drug to administer 40 more patients for six months, and that additional material would not be available for another 18 months. With this limited supply, they were limited in their ability to make sense of the dose.

There will be no one-size-fits-all approach to prepare for Project Optimus. Dose optimization-specific guidelines are not standardized by the FDA in other therapeutic areas, so the expectation of such for oncology developers holds their breath for a long time. Furthermore, as in other therapeutic areas, developers approach dose optimization in very different ways based not only on the nature of their programs but also on variables specific to them. optimization strategies depend on each molecule, its mechanism of action, the indication, the risk a sponsor is willing to take and the speed at which a developer is willing or able to move.[3]

Some cancer drug developers have asked: “What if we decide not to optimize the dose now? What is the risk?“Although it may seem that ‘wait and see’ is a simpler approach that avoids unnecessary overhead, developers should not hesitate. The FDA expects that efficacy will be evaluated at more than one dose level before approving a dose and regimen to be used in a pivotal study. By advancing and exploring additional doses, it helps developers take the most advantageous position and possibly avoid delays. Remember that, above all, preparation is the key to success.

Relation
[1] Moon H. FDA Initiatives to Support Dose Optimization in Oncology Drug Development: The Less the Better. translation clinical Pharmacol. 2022;30(2):71-74. doi:10.12793/tcp.2022.30.e9
[2] Tuntland, T., Ethell, B., Kosaka, T., et al. Implementation of pharmacokinetic and pharmacodynamic strategies in early research stages of drug discovery and development at the Novartis Institute of Biomedical Research. Front Pharmacol. 2014;5:174. Published July 28, 2014. doi:10.3389/fphar.2014.00174
[3] White paper from the Friends of Cancer Research. Optimizing dosing in drug development in oncology. Annual Meeting of the Friends of Cancer Research 2021. [Article]

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