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Publication Number
US-11224580-B2
Publication Date
2022-01-18
Expiration Date
Abstract
Treatment of intrahepatic cholestatic diseases by therapy with seladelpar or a salt thereof.
Core Innovation
The invention relates to treating an intrahepatic cholestatic disease by administering a therapeutically effective amount of a compound that is seladelpar or a salt thereof. The disclosed approach is directed to peroxisome proliferator-activated receptor delta (PPARδ) activation through seladelpar, including administration of seladelpar salts.
The disclosure focuses on intrahepatic cholestatic diseases and clinical biomarker endpoints, including alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It describes evaluation of reductions in ALP and ALP/GGT improvement in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
Clinical evaluation is described in phase 2 studies in PBC, including a high-dose PBC trial and a low-dose PBC trial, with ALP as a key endpoint and responder rates reported in the high-dose setting. The disclosure also describes an oral PSC study assessing ALP/GGT improvement while permitting concomitant ursodeoxycholic acid (UDCA).
Claims Coverage
The independent claim is directed to a method of treating an intrahepatic cholestatic disease with seladelpar or a salt at a defined daily amount range. Across the dependent claims, the inventive features are further specialized by disease type, salt form, and administration and dosing constraints, including oral dosing and specific daily amounts and dosing frequency limits.
Treating an intrahepatic cholestatic disease with seladelpar or a salt
Administering a therapeutically effective amount of a compound that is seladelpar or a salt thereof to treat an intrahepatic cholestatic disease.
Daily amount of seladelpar between 0.5 mg/day and 2 mg/day
Administering an amount between 0.5 mg/day and 2 mg/day when the amount of the compound is calculated as seladelpar.
Disease is one of primary biliary cholangitis, primary sclerosing cholangitis, progressive familial intrahepatic cholestasis, or Alagille syndrome
Where the intrahepatic cholestatic disease is primary biliary cholangitis, primary sclerosing cholangitis, progressive familial intrahepatic cholestasis, or Alagille syndrome.
Administering a seladelpar L-lysine dihydrate salt
Performing the method using the compound seladelpar L-lysine dihydrate salt.
Oral administration
Administering the compound orally.
Administering 0.5 mg/day, 1 mg/day, or 2 mg/day
Administering the compound at an amount of 0.5 mg/day, 1 mg/day, or 2 mg/day.
Dosing frequency between once per week and every other day
Performing the method by administering the compound between once per week and every other day.
Claim coverage centers on treating intrahepatic cholestatic diseases using seladelpar or a salt with a therapeutically effective daily amount calculated as seladelpar in the 0.5 mg/day to 2 mg/day range, with dependent coverage narrowing to particular named disorders, specific salt form, oral administration, specific daily dose values, and dosing frequency limits.
Stated Advantages
Reductions in ALP in primary biliary cholangitis are reported, including strong ALP reductions and high responder rates in the high-dose trial.
Dose-dependent ALP reductions are reported in the low-dose PBC trial.
No pruritus is reported in the low-dose PBC trial.
No transaminase safety signals are reported in the low-dose PBC trial.
ALP/GGT improvement is assessed in an oral PSC study while permitting concomitant UDCA.
Documented Applications
Treating intrahepatic cholestatic diseases including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), progressive familial intrahepatic cholestasis (PFIC), and Alagille syndrome (AS).
Phase 2 clinical evaluation of seladelpar in PBC, including a high-dose PBC trial and a low-dose PBC trial with ALP and responder outcomes.
Oral PSC study assessing ALP/GGT improvement while permitting concomitant ursodeoxycholic acid (UDCA).
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