NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

One needs to contemplate the purpose of surrogate endpoints and crossovers. Typically, if someone is on a trial, once they progress, there really is not standard of care. The length of time until passing is a median of 8 months from the point of progression. Not very long.

The reason why the FDA created the accelerated approval program was to allow a shorter more humane path to initial approval. Both treatment arm and placebo arm get to receive therapy, and, if their doctor concurs, use additional treatments as well.

The original discussion on this matter was about whether the patients knowing they are going to be getting treatment has implications for the trial. With a crossover, it is accepted that the trial is confounded to some extent. The primary endpoint is untainted, allowing accelerated approval, while the secondary endpoint is somewhat confounded. That is the humane nature of the crossover arm.

If a post approval confirmatory open label trial is needed to confirm O.S., the rules allow for that possibility. Personally, I expect PFS to be so significant and strong, that it will pull (if you will) O.S. through by a fairly wide margin, despite the crossover arm.