The MHRA’s draft guidance on the use of Real-World Evidence (RWE) and External Control Arms (ECA) is a key positive development for DCVax-L.
As you know the DCVax-L’s marketing application is built entirely on an ECA model, using real-world patient data to demonstrate efficacy in newly diagnosed and recurrent glioblastoma (GBM). This is not standard regulatory practice, it falls outside the traditional randomized controlled trial (RCT) model.
The MHRA explicitly states in its draft:
“There is no general scenario where the use of RWD external controls is explicitly ruled out.”
=> This is a clear defense of ECA-based submissions and a signal that DCVax-L’s methodology is valid in principle.
The guidance highlights situations where RCTs are unethical or unfeasible, such as:
Rapidly fatal diseases like GBM
Situations where it is unethical to assign patients to “no treatment” or placebo
=>This directly applies to DCVax-L: forcing GBM patients into placebo arms can be ethically unjustifiable, making ECA the only viable option.
Unless anyone knows about another application based on ECA RWD the MHRA is reviewing
The publication timing (May 2025) is telling:
The DCVax-L application has been under review for 18+ months
The draft was launched just weeks before a likely final decision
This shows MHRA is solidifying the policy foundation for approving non-RCT oncology therapies
The MHRA is not distancing itself from ECA — it is institutionalizing and publicly defending it. That’s not something you do before rejecting a drug built on ECA. It’s what you do when you’re preparing to approve and need a formal framework to support that decision.
In my view, the MHRA launched this public consultation for political, not scientific, reasons. The science around ECA/RWD is already well understood inside the MHRA. They’ve had the DCVax-L data for over 18 months. They’ve had time for site inspections, RFIs, CHM review, and even GMP recertifications.
Because approving DCVax-L a first-in-class immunotherapy, with no RCT, no FDA approval, and full reliance on ECA, would be a major precedent, and likely draw media, academic, and institutional scrutiny. Inviting public comment before June 30 gives the MHRA political air cover.
It allows them to say: “We followed a consultative, transparent process. We listened to all stakeholders before making this decision.”
In other words: the consultation is about legitimizing the decision they’re preparing to make, not about learning anything new.
AI
