Ann: Azer-cel Hits Major Milestone in Phase 1b CAR T Trial, page-218

Hi Hrdwk

According to the FDA's own website, you can actually apply for Breakthrough Therapy designation right from the start - ie at Phase 1:

"The Food Drug and Cosmetic Act (21 USC 356) states that a request for a breakthrough therapy designation may be made concurrently with, or at any time after, the submission of an application for [the IND]."

They do suggest that it should be requested no later than the end of a Ph 2 trial, and "before initiation of the clinical trial(s) intended to serve as the primary basis for demonstration of efficacy "

Source: The FDA's own website. Read point 5 on this page: https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies

I think submitting the application "concurrently" with the IND would be rare, because the full Guidelines document states clearly that you need to base it on "preliminary clinical evidence" and that usually isn't available at the initial IND application (which would be based on preclinical studies).

The exact wording is: "Section 506(a) of the FD&C Act provides for designation of a drug as a breakthrough therapy“. . . if the drug is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." Source: p. 10 of the FDA's "Guidance For Industry - Expedited Programs for Serious Conditions." https://www.fda.gov/media/86377/download

Implications for Azer-Cel-Cel:

I believe the results from the Phase 1 trial completed by Precision Biosciences for Azer-Cel-cel in "relapsed or refractory (R/R) non-Hodgkin lymphoma" already meet the requirements for Breakthrough Therapy designation, and I would think that that IMU has submitted an application for Breakthrough Therapy designation for Azer-Cel when they did the paperwork for the Ph 1b trial which has just started. (note: Precision BioSCiences already held "orphan drug designation for azer-cel from the U.S. Food and Drug Administration for the treatment of ALL and MCL, as well as Fast Track Designation for azer-cel for the treatment of B-ALL.." Source: https://precisionbiosciences.com/pipeline/clinical-trials/ ).
If I am correct, we will know fairly soon, because the FDA has to make a determination within 60 days of the request being lodged.

Implications for Vaxinia:
With regard to Vaxinia I think the data announced last Tuesday may also meet the requirement for Breakthrough Therapy: "preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development." My feeling is that IMU has probably already submitted the Breakthrough Therapy designation request - which is why LC was just saying "Stay tuned."

Cheers

Dave