Itch is common in people with PBC. Currently available treatments are not always effective and may have side effects. In PBC, the bile ducts in the liver become damaged which causes the build-up of bile acid salts in the body. This may cause some patients to experience persistent itching (pruritus).
The drug being developed by GSK is currently called GSK2330672. Itis being developed as a tablet to treat the PBC itch. Bile passes from the liver into the intestines where it helps with the digestion of food. Some of the bile is then taken back up into the blood and returned to the liver. GSK2330672 blocks the uptake of bile from the intestines. It is anticipated that this will allow the chemicals that cause the itch to be lost from the body in a person’s stool.
How to get involved in the study
GSK2330672 has already been tested in PBC patients in a small study. This larger study aims to find out which dose and dose frequency improves itch and if it has an effect on the underlying PBC disease. The study will test a range of doses to compare the effect, safety and how well it is tolerated by patients with moderate to severe itch due to PBC.
In Canada, the study is based in 5 research centres in Montreal, Winnipeg, Calgary, Edmonton and London. The study involves 7 visits at the study site and 1 final telephone contact with the study doctor or nurse. Patients participating in this study will receive reimbursement of their travel expenses and compensation for meals and refreshments for 2 of the visits which are expected to last between 2 and 5 hours.
GSK2330672 is currently being evaluated in a Phase 2b study. When the study is completed at all the study sites, the data will be analyzed.
CymaBay announced positive interim results from its ongoing low-dose Phase 2 study of seladelpar in patients with primary biliary cholangitis (PBC), a life-threatening and life-limiting chronic cholestatic liver disease. In the first part of the study, patients at high risk of disease progression, with an inadequate response to ursodeoxycholic acid (UDCA), as characterized by a persistent elevation in alkaline phosphatase (AP), or who were intolerant to UDCA, received either 5 mg or 10 mg of seladelpar once-daily. A planned interim analysis of the first 24 patients enrolled in these two dose groups demonstrated after 12 weeks of treatment a significant AP reduction from baseline of 39% and 45% for the 5 mg and 10 mg groups, respectively. On seladelpar, 45% of patients in the 5 mg and 82% of patients in the 10 mg dose groups had AP values < 1.67 times the upper limit of normal (ULN). AP is an established surrogate marker of disease progression in PBC, and reaching a level of < 1.67 x ULN is a key component in the composite endpoint used for regulatory approval.
Alongside substantial reductions in AP, patients in both dose groups experienced decreases in other liver markers of cholestasis including gamma glutamyl transferase and total bilirubin. Seladelpar also improved metabolic and inflammatory markers with patients experiencing decreases in low-density lipoprotein-C and high sensitivity C-reactive protein.
There were no serious adverse events and no safety transaminase signal was observed at either dose. Instead, mean transaminase levels decreased over the course of treatment, further supporting seladelpar’s anti-inflammatory activity. Consistent with prior studies, there was no signal for drug-induced pruritus.
After sharing preliminary results from the study, the FDA has agreed to allow continuation of seladelpar treatment beyond six months for the 5 mg and 10 mg doses.
“The data emerging from this study are impressive and support our hypothesis that lower doses of seladelpar than previously studied retain strong efficacy without raising a concern with transaminase elevations. We also see that seladelpar activity is not associated with drug-induced itch, an important benefit for patients with PBC. If these results are maintained over longer periods, we think that seladelpar could offer patients significant advantages over existing treatments,” said Professor Gideon Hirschfield, Centre for Liver Research, University of Birmingham, UK.
Dr. Pol Boudes, Chief Medical Officer of CymaBay added, “We’d like to thank the investigators and their staff as well as the patients and their families for their tremendous support. These interim results support the potent anti-cholestatic and anti-inflammatory effects of seladelpar. We are particularly excited about the FDA’s decision to allow dosing of seladelpar beyond six months enabling us to turn our attention towards planning the Phase 3 program.”
“The clinical and regulatory progress to date represent meaningful advancement in the development of seladelpar for patients with PBC,” said Sujal Shah, Interim President and CEO of CymaBay. “We are very encouraged by these results and the potential for seladelpar to improve treatment alternatives in PBC and other chronic liver diseases.”Read the full results of the “Seladelpar Interim Data Phase 2 Low Dose Study in PBC” by clicking here
The Canadian PBC Society is excited to share that a new treatment option for PBC is on it’s way, thanks to the recent Canadian approval of Ocaliva , otherwise known as obeticholic acid or OCA. According to a recent release by Intercept Pharmaceuticals, Health Canada has issued a conditional Notice of Compliance for Ocaliva, which is indicated for the treatment of PBC, in combination with URSO, or as monotherapy for those who cannot tolerate URSO.
This is the first new treatment for PBC in 20 years. “I’m thrilled that another treatment has finally been approved. I have spoken to so many patients that have been waiting for other treatments to become available because URSO isn’t working for them,” said Gail Wright, Canadian PBC Society President. “Our community is so energized by this news, and we look forward to our members being able to manage their disease more effectively.”
We anticipate that patients will be able to receive access to OCA in a number of different ways, including private insurance, provincial pharmacare plans and compassionate support programs. We’ll be happy to provide more details as they come available. Read full press release