dm+d

Unassigned

New Medicines

Familial hereditary nephritis (Alport syndrome)

Information

New molecular entity
Reata
Reata

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Yes
Oct 21Filed in the EU for the treatment of patients with CKD caused by Alport syndrome. The MAA submission is based on data from the PIII CARDINAL trial. In the US, a Prescription Drug User Fee Act (“PDUFA”) date has been set of February 25, 2022 [12].
Apr 21Filed in US and announced plans to file in EU Q421 [11]
Feb 21Bardoxolone methyl is considered by analysts to be the fourth most anticipated drug launch of 2021 [10].
Nov 20Reata Pharmaceuticals announce intention to submit NDA to US FDA for accelerated approval of bardoxolone methyl in Hereditary nephritis in first quarter of 2021. There are also plans to file in EU [8].
Feb 20In its latest annual report, Reata states that it plans to proceed with the submission of regulatory filings this year for marketing approval in the US and is preparing for a potential commercial launch of bardoxolone in Alport syndrome in the US; no mention of plans to file in the EU so presume this is not to happen in 2020. However, Reata does state that outside of the US it plans, either alone, or with new collaboration partners, to commercialise its products. It is refining its strategy and market assessments with respect to a potential launch in the EU [7].
Dec 19Also has orphan drug status in EU [5].
Nov 19Based on positive PIII CARDINAL results, and subject to discussions with regulatory authorities, Reata plans to file for marketing approval in the US and internationally [5].
Oct 19Reata announces reacquisition of development, manufacturing and commercialisation rights concerning its proprietary Nrf2 activator product platform originally licensed to AbbVie, for territories outside of the US with respect to bardoxolone methyl [5].
Jul 17US FDA grants orphan drug status bardoxolone methyl for Alport Syndrome [3].

Category

Nrf2 gene activator
Alports syndrome (AS) is the most common hereditary nephritis, accounting for 3% of end stage kidney disease (ESKD) in childhood. Disease frequency is estimated at 1:5,000. Males are more severely affected than females [1].
Familial hereditary nephritis (Alport syndrome)
Oral

Trial or other data

Nov 20Reata announce that Phase III CARDINAL study of bardoxolone in patients with CKD caused by Alport syndrome met its primary and key secondary endpoints at the end of Year 2. At Week 100, in the intent-to-treat population, which included eGFR values for patients who either remained on or discontinued study drug, patients treated with bardoxolone had a statistically significant improvement compared to placebo in mean change from baseline in eGFR of 7.7 mL/min/1.73 m2 (p=0.0005)[9]
Oct 20Reata Pharmaceuticals completes phase II/III CARDINAL trial. The phase III portion of the trial met its primary endpoint of change in estimated glomerular filtration rate (eGFR) at week 12 and 48 [8].
Nov 19Positive topline year 1 results from PIII CARDINAL trial of bardoxolone methyl in pts with CKD caused by Alport syndrome announced. This international, multi-centre, double-blind, placebo-controlled, randomised pivotal trial enrolled 157 pts (15% of whom were children). They were randomised 1:1 to bardoxolone or placebo. After 48 weeks, the mean eGFR in pts on bardoxolone improved by 9.50 mL/min/1.73 m2 vs. placebo (p<0.0001). After 48 weeks of treatment and a 4 week withdrawal period, pts given bardoxolone retained an improvement in their eGFR of 5.14 mL/min/1.73 m2 vs. placebo (p=0.0012). Bardoxolone was well-tolerated.[5]
Dec 18NCT03019185 now due to complete Dec 19.
Jul 17PII/III (NCT03019185) study due to complete collecting primary outcome data in Jan 19 [4].
Jun 17Reata commence PII/III CARDINAL trial of bardoxolone methyl in patients with AS (NCT03019185). Primary outcome measure is increase in eGFR from baseline [2].

Chronic kidney disease in autosomal dominant polycystic kidney disease (ADPKD), IgA nephropathy, type 1 diabetic CKD, and focal glomerulosclerosis (FSGS)

Information

New molecular entity
Reata
Reata

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

Activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling
A large primary care study (practice population 162,113) suggests an age standardised prevalence of stage 3-5 CKD of 8.5% [1].
Chronic kidney disease in autosomal dominant polycystic kidney disease (ADPKD), IgA nephropathy, type 1 diabetic CKD, and focal glomerulosclerosis (FSGS)
Oral

Pulmonary hypertension associated with connective tissue disease

Information

New molecular entity
Reata
Reata

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Nrf2 gene activator
Prevalence of PAH is estimated at 15-52 per million [2].
Pulmonary hypertension associated with connective tissue disease
Oral