On Monday, April 23, 2018, Prothena the failure of its registration trials for NEOD001 to treat AL amyloidosis to: meet its primary and secondary endpoints (Pronto); and futility analysis (VITAL). The program is being discontinued.

These were indeed very bad results.

We are unsurprised by the primary endpoint failure. Prothena is working within the toughest indications. It makes even cancer treatment look straightforward. We are surprised that there was no redeeming trend found in the data.

We would not be surprised that eventually Prothena finds recruitment issues between and within trials, but it will be unlike the obvious problems found with Capricor. It will be more like Corcept Corcept eventually found underneath the data even for that last . We don't think it will eventually be so straightforward for Prothena - there will be multiple issues to investigate. It is part of the nature of the beast in this area. Prothena must indeed walk away.

As for us, there’s a reason why we have a guideline for watching only one CNS company at a time. We just saw it. The CNS and misfolded protein arena is still very difficult, and the science is much less understood than other areas.

If you have good results, even in Phase 2a for metabolic endpoints, you will likely see something in later trials. BioMarin (lysosomal storage diseases) and Corcept (Cushing’s) are good examples. Even with cancer programs, you see a straighter line. You may not see success in the final Phase 3 trials, but you immediately apprehend the issues for falling short.

We concede to the overall caution from critics of Prothena’s research methods. This speaks to the requirements for a robust, well-thought Phase 2 program. Even then, some investment caution is warranted.

Prothena will survive because of the Roche and Celgene partnerships. We fear PRTA will not get respect, not until it has a Phase 3 success. The market may also punish PRTA even further. The Celgene partnership in particular brightens things because it increases the shots on goal in this difficult arena. Nevertheless, for PRTA investors, there’s no avoiding this ugly day, and perhaps an ugly season.

As we stated in the last note about Prothena:

“Because Prothena plays in a risky area, we have vented caution.

The odds are strong that there will be a trial failure in its current pipeline. While we like each program, the overall probability for at least a single failure is high. Prothena is deploying biologics into difficult diseases. It’s simply the nature of the biotech beast.

Do we hate Prothena? Absolutely not!

This is just simple probability.

Now that Prothena is assured of several shots to the clinic, the overall probability for meaningful success is escalated.”

While we like the Prothena scientists, the probabilities for overall success dims with each failure. We remain true to our earlier assertions. With everyone else, we will also take another hard look and await further post-mortems about this last “just discontinued” program.

(At the time this was written, one or more BioWatch staff own a long position in PRTA)

This blog post is from The Biotech Watcher

And about us, see http://alanhobbes.blogspot.com/2014/12/welcome-to-my-personal-thoughts-about.html

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