
Hello Regulatory Scientists,
Today, let’s dive into the journey of Balversa (erdafitinib) from receiving an FDA Complete Response Letter (CRL) to achieving approval. This case study provides valuable insights and lessons that can guide companies developing new drugs today.
Regulatory History and Initial Submission
Drug: Balversa (erdafitinib)
Mechanism of Action: FGFR (fibroblast growth factor receptor) inhibitor, which blocks the activity of FGFR proteins involved in the growth of cancer cells
Indication: Treatment of locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations
Initial Submission Date: June 2018
The Complete Response Letter (CRL)
CRL Date: October 2018
CRL Concerns:
- Clinical Data Requirements: The FDA requested additional data to confirm the efficacy and safety of Balversa in the target population.
- Biomarker Validation: Concerns about the validation of biomarkers used to identify patients likely to benefit from the drug.
- Manufacturing Process: Issues related to the consistency and quality of the drug’s manufacturing process.
Resubmission Strategy
Janssen Pharmaceuticals, the company behind Balversa, implemented a comprehensive strategy to address the FDA’s concerns:
- Additional Clinical Data: Conducted further studies to gather more robust data on the drug’s efficacy and safety in patients with FGFR3 or FGFR2 genetic alterations.
- Biomarker Validation: Provided additional data and analyses to validate the biomarkers used to identify suitable patients.
- Improved Manufacturing Processes: Implemented improvements in the manufacturing process to ensure consistency and quality.
- Continuous FDA Engagement: Maintained open lines of communication with the FDA to ensure alignment on the resubmission strategy and clarify any outstanding questions.
Resubmission Date: December 2018
Outcome
Approval Date: April 2019
Balversa was approved for the treatment of locally advanced or metastatic urothelial carcinoma with FGFR3 or FGFR2 genetic alterations, offering a new targeted therapy option for patients.
Lessons Learned
The journey of Balversa from CRL to approval highlights several key lessons for drug developers:
- Comprehensive Data Collection: Providing extensive clinical data to support the efficacy and safety profile of the drug is essential to addressing FDA concerns.
- Biomarker Validation: Ensuring robust validation of biomarkers is crucial for targeted therapies, helping to identify the right patient population.
- Improved Manufacturing Standards: Ensuring the quality and consistency of the manufacturing process is vital for regulatory approval.
- Continuous FDA Engagement: Maintaining open and ongoing communication with the FDA helps align development efforts with regulatory expectations.
Relevance for Current Drug Developers
For companies developing drugs today, the Balversa case underscores the importance of strategic planning and meticulous attention to detail in the regulatory process. Here are some takeaways to help avoid a CRL and achieve first-cycle approval:
- Thorough Pre-Submission Preparation: Ensure that all aspects of your submission, including clinical data, biomarker validation, and manufacturing processes, meet FDA standards.
- Proactive Risk Management: Identify and address potential risks early in the development process to prevent issues from arising during FDA review.
- Engage with the FDA Early and Often: Regular interactions with the FDA can provide valuable guidance and help steer the development process.
- Invest in Quality Data: Prioritize the collection of high-quality, detailed safety and efficacy data to support the submission.
- Utilize Advisory Committees: Seek feedback from advisory committees to validate data and address potential concerns.
By learning from the Balversa resubmission experience, current drug developers can better navigate the regulatory landscape, avoid common pitfalls, and increase the likelihood of a successful first review cycle approval.
Stay diligent and strategic,
CERES Regulatory Services