DURHAM, N.C. (May 16, 2023) – The U.S. Food and Drug Administration (FDA) and the National Cancer Institute collaborate on the Oncology Center of Excellence (OCE) Project Optimus, which aims to optimize oncology drug development through innovative trial designs, validated biomarkers, and consensus on clinical endpoints. The new draft guidance for industry issued by the FDA in January 2023, “Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases,” is a part of this effort. Within this guidance, the FDA explores the historical pattern of Phase I trial design reflecting a need to find the maximum tolerated dose (MTD) while overlooking opportunities to optimize dosage. While this approach effectively identified the optimal dosage for cytotoxic chemotherapy drugs, modern targeted oncology therapies often require a revised strategy.

“It is imperative to find the right dose with the right patient at the right time,” said President of D2V Clinical and former senior FDA reviewer Walt Cao. “Identifying the optimal dose during the early phases of oncology clinical trials is crucial in finding the balance between acceptable toxicity and clinically meaningful response. Due to the long-term nature of targeted therapies versus the specified time frame in which non-targeted therapies are administered, targeted therapies should be assessed in a way that allows us to identify the highest level of efficacy associated with toxicity levels that will not render the therapies unviable for continued use in the long term.”

Identifying the optimal dosage of a drug is crucial for both patients and drug approval processes. It ensures that patients receive the maximum clinical benefit of the drug while minimizing potential side effects. Moreover, during the New Drug Application (NDA) or Biologic License Application (BLA) review process, the clinical benefits of a drug must outweigh the risks for it to be approved. Therefore, the dose optimization strategy must be carefully planned and executed during Phase I studies to ensure that the drug meets the necessary efficacy and safety criteria for approval by regulatory agencies such as the FDA. As drug development becomes increasingly complex, optimizing the dosage of a drug remains critical in achieving successful clinical outcomes and obtaining regulatory approval.

“在第一阶段帮助客户时，我们的首要任务之一是帮助他们为合适的患者找到合适的剂量。我们可以限制暴露于无效剂量的患者数量，与此同时，临床研究方案的设计可以用较少的患者数量来回答科学问题，”Cao 说。 “我们致力于在早期阶段的研究中做到卓越，因为可以避免导致这些问题的错误。基于科学的方案设计将从根本上帮助申办者以更少的患者达到 I 期和 II 期的目标，并在早期看到疗效信号。”

作为 FDA 的前高级审评员，我们的监管专家 Cao 在评估批准的药物剂量优化策略方面拥有丰富的经验。 Cao 了解监管环境的复杂性和复杂性，可以提供有关优化药物开发过程以满足必要的疗效和安全标准的宝贵见解。 如果您想了解更多关于剂量优化对监管批准和患者利益的重要性，请立即联系我们。