New FDA Guidance to Support Ultra-Rare Disease Drug Development

Antisense oligonucleotide (ASO) drug products target a specific sense mRNA to modulate gene expression in living cells and have been used successfully to treat diseases where the pathogenic mutation has been identified.   

For patients with an ultra-rare genetic disease, development of an individualized ASO drug product tailored to that patient’s specific genetic variant may be the only viable therapeutic option.  

One hurdle to the development of such drugs for very small patient populations, which may consist of only 1 or 2 identified patients, has been the lack of a clear regulatory pathway.  

The FDA’s newest recommendations on clinical and CMC considerations for Investigational New Drug (IND) applications for the development of individualized ASO drug products for severely debilitating or life-threatening diseases join ASO guidance from earlier last year to further clarify the regulatory pathway for diseases identified in very few patients.  

These guidances will help establish a functional regulatory environment by providing clear administrative and procedural, preclinical, manufacturing, and clinical regulatory guidance to support ongoing efforts to discover and develop these life-changing treatments for ultra-rare patient populations.  

See a list of recent FDA ultra-rare disease recommendations and guidance for individualized antisense oligonucleotide drug products intended to treat severely debilitating or life-threatening genetic disease:  

IND Submissions for Individualized Antisense Oligonucleotide Drug Products: Administrative and Procedural Recommendations Guidance for Sponsor-Investigators 

This draft guidance outlines the administrative and procedural aspects of interacting with FDA on development programs for individualized ASO drug products.  

Nonclinical Testing of Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases Guidance for Sponsor-Investigators 

This draft guidance outlines the nonclinical information the FDA recommends to support an IND application for an individualized ASO drug product.  

IND Submissions for Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life Threatening Disease: Clinical Recommendations Guidance for Sponsor-Investigators 

This draft guidance outlines the clinical considerations for an IND submissions to support the initial and continued administration, dosing, and clinical monitoring of an individual with an individualized ASO drug product.  

IND Submissions for Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases: Chemistry, Manufacturing, and Controls Recommendations Guidance for Sponsor-Investigators 

This draft guidance outlines the recommendations regarding the CMC information to support an IND application for an individualized ASO drug.

by Dr. Amanda Beaster, Senior Manager of Regulatory Strategy

MMS Support for Ultra-Rare Disease 

In addition to our extensive experience across various rare disease indications, MMS launched a pro-bono support program aimed at advancing research for rare diseases. Within this program, MMS will select from patient advocacy groups to provide complimentary regulatory assistance.

To apply for support, complete and send an application to the attention of the “Ultra-rare disease Assistance Program” by emailing media@mmsholdings.com. For details on MMS rare disease expertise, visit https://www.mmsholdings.com/rare-disease/.