Pyridorin

Analyst Outlook

Pyridorin’s (pyridoxamine; NephroGenex) trial program has been put on hold due to company finances

and lack of investor/partner interest, so could well be suspended. Datamonitor Healthcare includes the

drug here for completeness, since development has not yet been technically terminated. Pyridorin has

had several issues during its development. On the positive side, unlike other advanced competitors, its

Phase II trial showed evidence for a benefit of a change in creatinine, which is more directly related to

the Phase III endpoint than urinary albumin-to-creatinine ratio (UACR). However, there was no

difference on the measure in the overall trial, only in subgroup analyses. In addition, the initial pivotal

trial was testing patients with relatively high albuminuria levels, potentially greatly limiting its market

size. There is also a commercial issue that supplements with the same active ingredient are currently

available. Finally, NephroGenex would potentially be facing three major competitors with a great deal

of marketing experience.

Drug Overview

Pyridorin is a metabolic isomer of vitamin B6. It inhibits the formation of advanced glycosylation end

products (AGEs) (AGE formation is considered as a part of the normal aging process) via the following

mechanisms:

– Inactivating toxic carbonyl compounds and reactive oxygen species.

– Inhibiting the conversion of post-Amadori intermediates to AGEs by interfering with the redox metal

ions catalyzing the reaction.

AGEs are thought to be involved in the pathogenesis of diabetic nephropathy (DN) (Biomedtracker,

2016; Medtrack, 2016; NephroGenex, 2015, 2016).

Pyridorin is currently in Phase III development in the US and EU for the treatment of DN

(ClinicalTrials.gov identifier: NCT02065791).