
Hello Regulatory Scientists,
Today, let’s dive into the journey of Aliqopa (copanlisib) 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: Aliqopa (copanlisib)
Mechanism of Action: PI3K inhibitor, which inhibits phosphatidylinositol-3-kinase, a key enzyme involved in cell growth and survival
Indication: Treatment of relapsed follicular lymphoma
Initial Submission Date: December 2016
The Complete Response Letter (CRL)
CRL Date: March 2017
CRL Concerns:
- Manufacturing Issues: The FDA raised concerns about the quality and consistency of the drug’s manufacturing process.
- Additional Data Requirements: Request for more comprehensive clinical data to support the efficacy and safety profile of the drug.
- Risk Management Plan: Need for a detailed risk management plan to monitor and mitigate potential adverse effects.
Resubmission Strategy
Bayer, the company behind Aliqopa, implemented a comprehensive strategy to address the FDA’s concerns:
- Enhanced Manufacturing Processes: Made significant improvements to the manufacturing process to ensure consistency and quality.
- Additional Clinical Data: Conducted further studies and analyses to provide more comprehensive data on the drug’s efficacy and safety.
- Detailed Risk Management Plan: Developed a robust risk management plan, including detailed monitoring guidelines and patient education materials.
- 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: June 2017
Outcome
Approval Date: September 2017
Aliqopa was approved for the treatment of relapsed follicular lymphoma, providing a new option for patients who have failed other therapies.
Lessons Learned
The journey of Aliqopa from CRL to approval highlights several key lessons for drug developers:
- Addressing Manufacturing Issues: Ensuring the quality and consistency of the manufacturing process is crucial. Proactive improvements and rigorous quality control measures can prevent setbacks.
- Comprehensive Data Collection: Providing extensive clinical data to support the efficacy and safety profile of the drug is essential to addressing FDA concerns.
- Effective Risk Management: Developing and implementing a detailed risk management plan can help mitigate potential adverse effects and ensure patient safety.
- Continuous FDA Engagement: Maintaining open and ongoing communication with the FDA helps align development efforts with regulatory expectations.
- Leveraging Advisory Committees: Engaging with advisory committees can provide valuable feedback and support the resubmission process.
Relevance for Current Drug Developers
For companies developing drugs today, the Aliqopa 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, particularly manufacturing processes and clinical data, 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.
- Utilize Advisory Committees: Seek feedback from advisory committees to validate data and address potential concerns.
- Invest in Quality Data: Prioritize the collection of high-quality, detailed safety and efficacy data to support the submission.
By learning from the Aliqopa 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
