The FDA response to Lily's post-phase 2 donanemab accelerated approval application and NDA was interesting, and no doubt frustrating to the company. Their phase 2 had 131 patients on drug (about same on placebo). The drug was so effective in decreasing AB levels, the key biomarker endpoint, that fewer than 100 needed to complete a year's worth of dosing, and were stopped. Their efficacy testing did not stop, and went on the full 76 weeks, well over a year. All per the trial protocol.
In the complete response (ie, rejection) letter to the AA application, the FDA requested that Lilly provide data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab. Which it couldn't without a new trial.
A couple notes on this:
- So what if an AD drug was designed for 3 to 12 months dosing, depending on a patient's biomarker progress? Dosing must be for a year? What if some drug were found to need only 6 months dosing? It's a bizarre objection.
- Shows BP doesn't get 'favored' treatment.
- If at least 100 patients or more getting a year's drug exposure is somehow a de facto FDA minimum, for AA or regular approval, our phase 2b/3 amply meets it. At least the FDA cannot justify pointing to our small trial size as an approval objection. (They may do so anyway, but would be controversial in light of their donanemab rejection.)
At the Noble conf, around 18 minutes in Missling said "stay tuned to hear more" on our FDA discussions for AD. This of course could mean next month or next few quarters. If discussions are particularly favorable, it may be that we get Fast Track. We are not eligible for AA (needed FT first), but that could follow.
FDA will probably release results of its advisory committee on donanemab's bigger phase 3 in the next few months. That too will be of interest. If they reject, it can't be for not having enough 12-month dosing data. Nor efficacy, since it was slightly superior to lecanemab. If would have to be on safety.
