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Hello Regulatory Scientists, 

Today, let’s explore the journey of Aimovig (erenumab) 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: Aimovig (erenumab) 
Mechanism of Action: CGRP (calcitonin gene-related peptide) receptor antagonist, which helps to prevent migraine by blocking the receptor involved in migraine attacks 
Indication: Preventive treatment of migraine 
Initial Submission Date: May 2017 

The Complete Response Letter (CRL) 

CRL Date: November 2017 
CRL Concerns

  1. Manufacturing Issues: Concerns regarding the consistency and quality of the drug’s manufacturing process. 
  1. Labeling Requirements: Requests for revisions in the proposed labeling to better reflect the drug’s safety and efficacy profile. 
  1. Risk Management Plan: Need for a detailed risk management plan to monitor and mitigate potential adverse effects. 

Resubmission Strategy 

Amgen and Novartis, the companies behind Aimovig, implemented a comprehensive strategy to address the FDA’s concerns: 

  1. Manufacturing Process Improvements: Implemented significant upgrades to the manufacturing process to address consistency and quality concerns. 
  1. Enhanced Quality Control: Established stricter quality control measures to ensure the reliability of the drug’s production. 
  1. Revised Labeling: Made necessary revisions to the proposed labeling to clearly communicate the drug’s benefits and risks. 
  1. Risk Management Plan: Developed a robust risk management plan, including detailed monitoring guidelines and patient education materials. 
  1. 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: February 2018 

Outcome 

Approval Date: May 2018 
Aimovig was approved for the preventive treatment of migraine, marking a significant milestone in migraine management and providing a new option for patients. 

Lessons Learned 

The journey of Aimovig from CRL to approval highlights several key lessons for drug developers: 

  1. Addressing Manufacturing Issues: Ensuring the quality and consistency of the manufacturing process is crucial. Proactive improvements and rigorous quality control measures can prevent setbacks. 
  1. Clear and Accurate Labeling: Revising labeling to clearly communicate the drug’s benefits and risks is necessary for regulatory approval. 
  1. Effective Risk Management: Developing and implementing a detailed risk management plan can help mitigate potential adverse effects and ensure patient safety. 
  1. Continuous FDA Engagement: Maintaining open and ongoing communication with the FDA helps align development efforts with regulatory expectations. 
  1. Proactive Quality Control: Implementing stringent quality control measures ensures the consistency and reliability of the drug’s production. 

Relevance for Current Drug Developers 

For companies developing drugs today, the Aimovig 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: 

  1. Thorough Pre-Submission Preparation: Ensure that all aspects of your submission, particularly manufacturing processes and labeling, meet FDA standards. 
  1. Proactive Risk Management: Identify and address potential risks early in the development process to prevent issues from arising during FDA review. 
  1. Engage with the FDA Early and Often: Regular interactions with the FDA can provide valuable guidance and help steer the development process. 
  1. Invest in Facility Upgrades: Prioritize the improvement of manufacturing facilities to meet regulatory standards and ensure high-quality production. 
  1. Detailed Documentation: Provide comprehensive documentation to support the resolution of any identified issues. 

By learning from the Aimovig 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