EOP2@NDA Partners

The Drug and Biologics Team at NDA Partners can provide assistance for small and large companies in both near-term and long-term preparation for the critical End-of-Phase 2 (EOP2) decision point.

Effective drug and biologic development is an integrated succession of value-added technical decisions and regulatory interactions. In order to justify investment in the final phase of development (phase 3), a critically important program assessment of the adequacy of the knowledge generated in phases 1 and 2 is required that will inform the design and conduct of the lengthy and costly phase 3 confirming clinical trial(s). The immediate decision point prior to the initiation of the phase 3 program is referred to as the “end-of-phase 2” (EOP2), usually marked by an official EOP2 meeting with the FDA.

The goal of the Sponsor-FDA EOP2 meeting is to gain agreement with the FDA on the design of the phase 3 program, specifically the design of the phase 3 clinical protocol(s), the clinical trial efficacy and safety endpoints that are acceptable to both FDA and the sponsor, and the statistical analysis plan(s) (SAP).

The understanding and implementation of NDA Partners’ second, fourth, and fifth Development Principles for Optimal Product Development (“Product Readiness”, “Learning and Confirming”, and “Regulatory Collaboration”) are required to ensure a successful EOP2 meeting with FDA and other regulatory agencies. Identification of a dosage regimen that is highly likely to provide approvable evidence of effectiveness and safety in the phase 3 program is a particularly important prerequisite for a successful EOP2 meeting with FDA.

An earlier meeting with FDA during phase 2 is highly recommended — the end-of-phase 2A (EOP2A) meeting which follows demonstration of clinical Proof-of-Principle. The EOP2A meeting, encouraged by FDA[1], aims to provide FDA input into the planning of an informative phase 2B optimal dose identification study(s).

NDA Partners' expert services for the EOP2 stage of development include:

Assistance in design of a phase 2 program that will produce early Go/No Go decision-point knowledge and dose-response knowledge required for an informed EOP2 decision.
Preparation of sponsors for an EOP2A meeting with the FDA in which the sponsor can present their intended phase 2B program and obtain critical feedback and guidance from the FDA.
Assessment of the phase 1 and 2 knowledge generated as well as identification of the key EOP2 topics and issues for which a sponsor should seek FDA answers.
Assistance in the design and conduct of a sponsor’s internal EOP2 decision meeting.
Creation of focused EOP2 questions to ensure that the FDA response will be useful and informative (rather than a sponsor receiving an “It will be a review issue” response).
Assistance in preparing the required EOP2 briefing document so that it will provide focus on the key issues and include supporting data.
Generation of potential “Best Case” and “Worst Case” EOP2 meeting responses from the FDA.
Assistance in the advance preparation of informed and cogent sponsor replies to possible FDA responses to the EOP2 questions.
Participation in the rehearsals for the EOP2 meeting.
Attendance at the EOP2 meeting.
Assistance in the EOP2 debrief as the “neutral third party.”
Assistance in defining the post-EOP2 next steps and the design of the optimal path forward.

[1] Guidance for Industry End-of-Phase 2A Meetings. www.fda.gov/guidance, September 2009.