Anavex Life Sciences Corp (AVXL)

[XenaLives]

I have posted all of this before and it has been heavily discussed.

Nothing "seat of the pants" about it.

Sounds like dialogue to me.

B. Features of Fast Track Designation
1. Actions to Expedite Development and Review
There are opportunities for frequent interactions with the review team for a fast track product.
These include meetings with FDA, including pre-IND meetings, end-of-phase 1 meetings, and
end-of-phase 2 meetings to discuss study design, extent of safety data required to support
approval, dose-response concerns, and use of biomarkers. Other meetings may be scheduled as
appropriate (e.g., to discuss accelerated approval, the structure and content of an NDA, and other
critical issues).
In addition, such a product could be eligible for priority review if supported by clinical data at
the time of BLA, NDA, or efficacy supplement submission (see section VIII).

Page 9 - https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf

B. Features of Breakthrough Therapy Designation
1. Intensive Guidance on an Efficient Drug Development Program, Beginning as
Early as Phase 1
As discussed previously, breakthrough therapy designation will usually mean that the effect of
the drug will be large compared with available therapies. In such cases, the development
program for the breakthrough therapy could be considerably shorter than for other drugs
intended to treat the disease being studied. However, FDA notes that a compressed drug
development program still must generate adequate data to demonstrate that the drug is safe and
effective to meet the statutory standard for approval.13 Omitting components of the drug
development program that are necessary for such a determination can significantly delay, or even
preclude, marketing approval.
Sponsors can design efficient clinical trials in a number of ways. FDA will seek to ensure that a
sponsor of a product designated as a breakthrough therapy receives timely advice and interactive
communications to help the sponsor design and conduct a drug development program as
Contains Nonbinding Recommendations
14
efficiently as possible.14 During these interactions, the Agency may suggest, or a sponsor may
propose, alternative clinical trial designs (e.g., adaptive designs, an enrichment strategy,
crossover or N-of-1 design, use of historical controls) or use of an interim analysis by a data
monitoring committee.15 These trial designs may result in smaller trials or more efficient trials
that require less time to complete and may help minimize the number of patients exposed to a
potentially less efficacious treatment (i.e., the control group treated with available therapy).
Such approaches may be especially useful in studies in rare diseases. For example, single-arm
trials may be an important option in rare diseases with well-understood pathophysiology and a
well-defined disease course.
FDA anticipates that the review team and the sponsor will meet and interact throughout drug
development to address these and other important issues at different phases of development. In
addition, a sponsor should be prepared for a more rapid pace for other aspects of the drug
development (e.g., manufacturing (see section IX.A.), development of a necessary companion
diagnostic (see section IX.D.)).
2. Organizational Commitment Involving Senior Managers
FDA intends to expedite the development and review of a breakthrough therapy by intensively
involving senior managers and experienced review and regulatory health project management
staff in a proactive, collaborative, cross-disciplinary review. Where appropriate, FDA also
intends to assign a cross-disciplinary project lead for the review team to facilitate an efficient
review of the drug development program. The cross-disciplinary project lead will serve as a
scientific liaison between members of the review team (e.g., medical; clinical pharmacology;
pharmacology-toxicology; chemistry, manufacturing, and controls (CMC); compliance;
biostatistics), facilitating coordinated internal interactions and communications with a sponsor
through the review division’s regulatory health project manager.
3. Submission of Portions of an Application (Rolling Review)
FDA has determined that it is appropriate for a drug designated as a breakthrough therapy to be
able to obtain rolling review. Therefore, if FDA determines, after preliminary evaluation of
clinical data submitted by the sponsor, that a breakthrough therapy product may be effective, the
Agency may consider reviewing portions of a marketing application before the sponsor submits
the complete application (see Appendix 2).

Pages 13-14 - https://www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf