Friedreich's Failure Highlights Thinning Pipeline

Another failure in Friedreich’s ataxia, this time with Reata Pharmaceuticals’ (NASDAQ:RETA) omaveloxolone, has exposed a dearth of late-stage candidates for this indication.

After Horizon Pharma’s stumble with Actimmune last year there are no projects in phase III development and just five in phase II - and some of these seem to have stalled, providing another reminder of how tricky rare disease drug development can be (see table below).

The pipeline has thinned since the last time EP Vantage carried out this analysis - as well as Actimmune, two phase I projects have fallen by the wayside (Therapy focus - Clinging to options in Friedreich’s ataxia, September 1, 2016).

Commercial projects for Friedriech’s ataxia in phase II
Product Company Pharmacological class Trial ID
Omaveloxolone AbbVie/Reata Pharmaceuticals Nuclear factor erythroid derived 2 (Nrf2) activator NCT02255435 (Moxie) - part 1 failed
RT001 Retrotope Free radical scavenger NCT02445794 - hit, extension trial ongoing
Epicatechin Cardero Therapeutics Mitochondria targeted therapy NCT02660112 - results expected 2018
EPI-743 Edison Pharmaceuticals NADPH quinone oxidoreductase (NQO) 1 modulator NCT01962363 - concluded 2016, no results reported
NCT01728064 - concluded 2015, no results reported

JOT101 Jupiter Orphan Therapeutics CNS agent NCT01339884 - concluded 2012, mixed results
Source: EvaluatePharma.
Reata’s omaveloxolone could be next for the scrapheap. The first part of the phase II Moxie trial failed to meet its primary and secondary endpoints. The group said that there was a significant improvement on the modified Friedreich’s Ataxia Rating Scale (mFARS) over baseline. This scale was used as the secondary endpoint - but versus placebo, and here the drug did not show a significant benefit.

The trial also missed its primary endpoint, peak work during maximal exercise testing. Reata tried to talk up the positives by pointing to analysis in a subgroup of patients without a foot deformity associated with Friedreich’s called pes cavus, which causes high arched feet.