
Hello Regulatory Scientists,
Today, let’s explore the journey of Evenity (romosozumab) 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: Evenity (romosozumab)
Mechanism of Action: Sclerostin inhibitor, which increases bone formation and decreases bone resorption
Indication: Treatment of osteoporosis in postmenopausal women at high risk of fracture
Initial Submission Date: July 2016
The Complete Response Letter (CRL)
CRL Date: July 2017
CRL Concerns:
- Cardiovascular Safety: The FDA raised concerns about the increased risk of cardiovascular events observed in clinical trials.
- Additional Safety Data: Request for more comprehensive safety data to better understand the long-term safety profile.
- Risk-Benefit Analysis: Concerns that the benefits did not sufficiently outweigh the risks given the safety concerns observed.
Resubmission Strategy
Amgen and UCB, the companies behind Evenity, implemented a comprehensive strategy to address the FDA’s concerns:
- Additional Clinical Trials: Conducted further studies to gather more robust safety data, specifically focusing on cardiovascular risks.
- Enhanced Safety Monitoring: Provided additional data and analyses on the safety profile, with a focus on cardiovascular health.
- Risk-Benefit Reevaluation: Conducted a detailed risk-benefit analysis to better communicate the drug’s potential benefits relative to its risks.
- Patient-Focused Approach: Engaged with patient advocacy groups to highlight the unmet medical need and the impact of osteoporosis on women’s lives.
- 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: November 2018
Outcome
Approval Date: April 2019
Evenity was approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture, providing a new option for these patients.
Lessons Learned
The journey of Evenity from CRL to approval highlights several key lessons for drug developers:
- Robust Safety Data: Providing comprehensive and robust safety data is crucial to demonstrating a drug’s safety profile.
- Effective Risk Management: Developing and implementing a detailed risk management plan can help mitigate potential adverse effects and ensure patient safety.
- Clear Risk-Benefit Communication: Clearly communicating the risk-benefit balance, particularly in areas with unmet medical needs, is essential for regulatory success.
- Patient Advocacy Engagement: Engaging with patient advocacy groups can highlight the real-world impact of the condition and the need for new treatments.
- Continuous FDA Engagement: Maintaining open and ongoing communication with the FDA helps align development efforts with regulatory expectations.
- Utilizing 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 Evenity case underscores the importance of strategic planning and meticulous data collection 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 safety and efficacy 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 Evenity 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