Earlier this year, the United States Food and Drug Administration (FDA) issued draft guidance surrounding investigational new drug (IND) submissions for individualized antisense oligonucleotide (ASO) drug products. Because of the often-rare and progressive diseases covered by these drug products, the draft guidance emphasizes the importance of initiating interaction with FDA as soon as possible, including establishing a communication plan.
Confidentiality Concerns
One of the first things the FDA touches on in the draft guidance is the unique nature of ASO therapies. Because of their individualized essence, patients and family members may function more as collaborators than research subjects and may sometimes attend sponsor-FDA meetings. To that end, the FDA clarifies in the guidance that in the absence of a confidentiality agreement between the sponsor and the outside participant, “whatever the sponsor or FDA shares at a meeting about the application may be considered a public disclosure of the sponsor’s confidential information” and the FDA will seek written clarification of whether having a patient or family member present will constitute public disclosure. If a confidentiality agreement is in place, “FDA generally would not consider the presence of that outside participant at a scheduled meeting between the sponsor and FDA to trigger uniform access with respect to information discussed at that meeting.”
IND Submission Expectations
The draft guidance also lays out general expectation for IND submissions and the content and format for the pre-IND meeting package for ASO products, recommending that sponsors use electronic submissions to “facilitate and expedite review.”
FDA also provides direction for sponsors on the content of research IND applications, including the fact that the applications should include a justification for the individualized ASO drug product. In the guidance, FDA acknowledges that “it is unlikely that human data will be available at the time of the initial IND submission” and therefore, “only product manufacturing and quality information, bioinformatic (information related to the design of the oligonucleotide), and nonclinical data will support the safety of initiating administration to a participant,” making it critical that the nonclinical data be adequately presented and documented.
Other Topics Covered
Other topics covered in the draft guidance include ethical and human subject protection considerations, safety reporting, and annual reporting requirements.
It is important to also note what the draft guidance doesn’t cover. In the introduction to the draft guidance, the FDA notes that it only covers the IND submission process and that other considerations – including marketing and continued, long-term treatment – are excluded from the scope of the guidance, as are nonclinical data guidelines, clinical data guidelines, and product quality requirements.
FDA Statement
In a statement released with the guidance, Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research (CDER), said that these “N of 1” therapies have “a set of challenges and considerations not seen with the typical drug intervention” and that many of the rare diseases treated by ASOs are rapidly progressive, making time a critical factor in whether the affected individual is able to be helped by the treatment.
Cavazzoni also reflected on the fact that the draft guidance is only a “first step” along the way to bringing effective individualized treatments to patients safely and voiced her optimism that continued development of these “individualized drug products may spur gene sequencing that leads to the development of additional individualized drug products for the same disease (though perhaps caused by a different mutation).”