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AbbVie (North Chicago, IL) has dissolved its partnership with Reata Pharmaceuticals (Irving, TX) after nine years. The two companies were working together to develop, among other drug candidates, the therapeutic agent bardoxolone methyl for chronic kidney disease (CKD). The compound was moving along the approval pipeline until the FDA received findings that patients in the CKD treatment arm of a phase 3 study exhibited heart-related side effects, reported.

Now the drug is being tested in more specific populations: patients with autosomal dominant polycystic kidney disease, a genetic disorder, as well as in patients with CKD caused by Alport syndrome, also an inherited disease. If results from current trials prove positive, then Reata will be in a much better position financially, reports

“The deal is important to us because we get the rights to commercialized CKD indications on a worldwide basis,” said Reata CEO Warren Huff in a corporate statement. “Now we have all the rights, except those in southeast Asia, which are owned by our partner, Kyowa Kirin Co.”

AbbVie poured a total of more than $800 million into the partnership. The deal asks Reata to pay back $330 million in cash for the rights to the treatments, including bardoxolone, an orally available semi-synthetic triterpenoid, based on the natural product oleanolic acid. Pre-clinical studies indicated that the compound acts as an activator of the nuclear factor erythroid 2-related factor 2 (Nfr2) pathway. Nfr2 regulates expression of antioxidant proteins that protect against oxidative damage. Reata is also developing Nfr2 compounds to treat other diseases.

Another CKD drug candidate is moving to a phase 2 trial: DiaMedica Therapeutics’ (Minneapolis, MN) DM199, a synthetic form of human serine protease kallikrein, which plays an important role in kidney physiology, including blood flow, inflammation, fibrosis, and oxidative stress.

The phase 2 study will enroll about 60 patients with CKD. The two cohorts will include 1) patients with CKD caused by IgA nephropathy and 2) non-diabetic, hypertensive African Americans with CKD. African Americans are at greater risk for CKD than European Americans; those with the APOL1 gene are at even higher risk.

Primary endpoints of the study will include safety, tolerability, kidney function, and blood pressure. Kidney function will be evaluated by changes from the baseline level of estimated glomerular filtration rate and albuminuria, as measured by the ratio of urinary albumin to creatinine.