Case study:
Getting a Rare Disease Phase 3 Program Back on Track Through Global Regulatory Alignment
Background:
A US-based small biotech company approached Boyds as they were about to commence their Phase 3, single pivotal trial in a rare disease for which they had orphan designation. There was precedent in the therapy area, but only for one class of medicines that had a very different mode of action from theirs and no specific therapeutic area guidance in either the US or EU. They had conducted an end-of-Phase 2 meeting with the FDA, and upon filing the protocol, had received significant feedback. They had not yet spoken to any other regulators globally. Boyds were asked to provide support to determine the next steps to get them back on track.
Boyds approach
Boyds reviewed the interactions and feedback received to date and determined that the questions asked and corresponding positions had not been in sufficient depth to ensure buy-in from the Agency, including on the primary endpoint and sample size for the study.
They also flagged the need for advice from the EU, as an EU filing was planned in the future. Following informal interactions with the FDA, they determined a strategy to conduct a Type C meeting with the FDA to discuss the outstanding issues in more detail. They also proposed conducting EU Centralised Scientific Advice at the same time, so that briefing materials would be significantly reused to minimise the budgetary impact on the company.
Boyds also established that the client had not filed a Paediatric Investigation Plan (PIP), which was needed in the EU, even though they had orphan designation. This was particularly relevant as paediatric patients were included in the pivotal trial. Boyds determined the strategy for the EU PIP, including working closely with the client and Boyds subject matter experts on all elements of the quality, non-clinical, and clinical plan, including significant use of modelling and extrapolation approaches to minimise the need for clinical trials.
Boyds operationalised all of these elements globally, authoring high-quality documents for each interaction that leveraged existing content where possible for authoring and review efficiency.
Impact and Outcomes
The client received clear and actionable feedback on the Phase 3 protocol and was able to align this globally prior to enrolling patients, therefore, both maintaining the integrity of the study and ensuring a clear pathway to registration in the event of a positive trial. Boyds’ efficient turnaround of both the strategy and the supporting documentation minimised delays. The PIP was approved, clearing the pathway for a future EU filing. Boyds continues to work closely with the client.
Lessons learned:
- Consider the global fling strategy early and build this into which regulators should be approached for advice on a pivotal program, particularly where there is limited guidance or precedent
- Think about the global paediatric requirements in plenty of time, particularly where children will be included in the initial trials
- When interacting with a regulator, carefully consider the questions asked and the details given to ensure high-quality feedback is received that de-risks the program