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The Voxzogo Resubmission Journey: From FDA CRL to Approval 

Categories: Regulatory Rescue
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Hello Regulatory Scientists, 

Today, let’s explore the journey of Voxzogo (vosoritide) 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: Voxzogo (vosoritide) 
Mechanism of Action: C-type natriuretic peptide (CNP) analog that promotes endochondral ossification by antagonizing the fibroblast growth factor receptor 3 (FGFR3) pathway 
Indication: Treatment of achondroplasia, a genetic disorder that results in dwarfism 
Initial Submission Date: August 2020 

The Complete Response Letter (CRL) 

CRL Date: November 2020 
CRL Concerns: 

  1. Efficacy Data: The FDA requested additional data to confirm the clinical benefit of Voxzogo, particularly focusing on height improvement over an extended period. 
  1. Safety Data: Concerns were raised about the long-term safety profile, requiring more comprehensive data. 
  1. Manufacturing Process: The FDA noted issues related to the quality and consistency of the drug’s manufacturing process. 

Resubmission Strategy 

BioMarin Pharmaceutical, the company behind Voxzogo, implemented a comprehensive strategy to address the FDA’s concerns: 

  1. Extended Clinical Trials: Conducted further studies to gather more robust data on the efficacy of Voxzogo, focusing on long-term height improvement and other clinical benefits. 
  1. Enhanced Safety Monitoring: Provided additional data and analyses on the long-term safety profile, including monitoring for potential adverse effects. 
  1. Manufacturing Process Improvements: Made significant enhancements to the manufacturing process to ensure consistency and quality, including more rigorous quality control measures. 
  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: May 2021 

Outcome 

Approval Date: November 2021 
Voxzogo was approved for the treatment of achondroplasia in children aged five years and older with open epiphyses, providing a new therapeutic option for this rare genetic disorder. 

Lessons Learned 

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

  1. Comprehensive Data Collection: Providing extensive clinical data, particularly focusing on long-term efficacy and safety, is crucial to addressing FDA concerns. 
  1. Enhanced Safety Monitoring: Ensuring thorough understanding and management of the drug’s long-term safety profile can help mitigate regulatory concerns. 
  1. Manufacturing Process Improvements: Ensuring the quality and consistency of the manufacturing process is vital for regulatory approval. 
  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 Voxzogo 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, including clinical data, safety data, and manufacturing processes, 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 Quality Data: Prioritize the collection of high-quality, detailed safety and efficacy data to support the submission. 
  1. Utilize Advisory Committees: Seek feedback from advisory committees to validate data and address potential concerns, even if formal hearings are not required. 

By learning from the Voxzogo 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 

Picture of Asad Khan
Asad Khan