Currently Enrolling Patients for Phase 2 Study

Currently enrolling patients for Phase 2 Study in Canada, USA, UK and Germany. No placebos will be used, while dosages may differ between participants. Health Canada and FDA approve this 52 week study. Principal investigators in Canada: Dr. Mark Swain (Calgary);  Dr. Hemant Shah (Toronto)


An Update from Cymbay

Background

CymaBay Therapeutics is a small biotech company located in the San Francisco Bay Area. So far, we have 22 employees. The company is publicly traded on the NASDAQ market (ticker symbol CBAY). For the last two years we have conducted two studies with seladelpar (formerly known as MBX-8025) for the treatment of primary biliary cholangitis (PBC).

The so-called ‘CB8025-21629’ is our second study evaluating the effects and safety of seladelpar on PBC patients. Its main objective is to define what is the appropriate dose of seladelpar to be used. The study is open to patients who have high alkaline phosphatase (AP), a marker of liver function, and are not responding well enough to UDCA (sometimes also called ‘urso’ or ‘ursodiol’) or who cannot tolerate UDCA. All patients receive treatment with seladelpar, there is no placebo, but the dose is chosen at random (5 or 10 mg/day, orally). The study treatments are not masked, so patients and physicians know the dose they receive.

Study Progress

When the first 24 patients enrolled in ‘CB8025-21629’ reached 12 weeks of treatment we evaluated their progress while the study is continuing. This is called an ‘interim analysis’. The goal was to get an early look to see if the dose is correct, if seladelpar is well tolerated and effective and, eventually, speed-up the program and plan its next stage.

We compared patient results before treatment and during treatment. At 12 weeks, significant AP decreases were seen in the seladelpar 5 mg and 10 mg groups, 39% and 45%, respectively. This suggests that the liver is functioning better. Total bilirubin and gamma glutamyl transferase (GGT), other tests of liver function, also improved. These results also suggest that seladelpar, at the doses used, exerts a favorable impact on cholestasis (the retention of bile). Cholestasis is a prominent issue in PBC. We also saw a decrease in an important marker of inflammation called the C-reactive protein. This protein is secreted by the liver when it is faced with an inflammatory injury such as PBC.

Overall, there were no indication of increased pruritus with seladelpar. This was something we already knew from our first study, but which was important to confirm in this second study. In addition, seladelpar seemed well tolerated. For instance, no patient reported a serious adverse event.

Based on these results, Health Canada and the US-FDA agreed that we can treat patients with seladelpar 5 mg and 10 mg for longer than six months. The CB8025-21629 study now has a 52-week seladelpar treatment period. We are also planning to extend seladelpar treatment beyond one year with a new long-term extension study that will be open to patients who have participated in a seladelpar study, assuming that they tolerate the drug well. Treatment in the long-term study will continue until seladelpar is approved in Canada or the program is discontinued.

Canadian Study Sites

Study ‘CB8025-21629’ is currently enrolling patients in 4 countries (Canada, United States, United Kingdom and Germany). We have two sites open in Canada:

University of Calgary Liver Unit, Calgary, Alberta, Canada, T2N 4Z6

Principal Investigator: Mark Swain, M.D.

Study Coordinators: Pam Crotty, Shirley Cole

Phone: 403-210-3800

 

Toronto Centre for Liver Disease, Toronto, Ontario, Canada, M5G 2C4

Principal Investigator: Hemant Shah, MD

Study Coordinator: Teresa Bianco

Phone: 416-340-4584

 

Next Steps

With these developments, we are now looking to the next phase of the seladelpar program. This next phase is called the ‘confirmatory’ phase, or phase 3. We need to reproduce these encouraging data on a bigger scale, with a larger study and a treatment duration of at least one year. This study is sometimes also called the ‘registration’ study. A similar study served as the basis for the registration of Ocaliva (the ‘POISE’ study).

 

If the results of this confirmatory study are positive, the data collected will be submitted to health authorities to file a registration package and request an authorization for physicians to prescribe seladelpar to their PBC patients outside of a clinical study. The registration package is a very comprehensive dossier that includes data from clinical studies but also data from multiple non-clinical studies (e.g. toxicology) as well as data on how the drug is made and prepared (manufacturing process).

CymaBay’s intent is to use the coming month to present its plan for the confirmatory study to health authorities. This includes Health Canada, as well as the US-FDA, the European Medicine Agency and potentially other countries around the world.

 

CymaBay is very thankful to the PBC patients who participated and continue to participate in our studies. We totally appreciate their dedication and we all do our best to conduct the best research possible. We will use the results of the ongoing study to justify starting the agreed upon confirmatory study as quickly as possible. Our wish, if everything goes well, is to start this study in the second part of 2018. We’ll probably need to grow beyond 22 employees to achieve this challenge!

Important Update

Obeticholic acid (Ocaliva) has recently been licenced in Canada for the treatment of people with PBC who have not fully responded to, or who are unable to tolerate, Ursodeoxycholic acid. You may have seen a recent news report from the U.S. regarding some serious adverse outcomes for PBC patients whose prescribed dose of Ocaliva was significantly higher than that recommended and approved by the FDA. This appears to be an issue primarily among patients who have advanced cirrhosis, some of whom have experienced liver injury, liver failure, and even death. We feel it’s important to make sure you are aware of this issue. If you are being treated with Ocaliva and have any questions or concerns about the appropriate dosage level for your stage of PBC, you should talk to your doctor.

New PBC treatment for Itch now in clinical trials in Canada


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.

Current Status

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.  Read more about this study here.

Positive Interim Results for Phase 2 PBC Drug Trial

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

First new PBC treatment in 20 years approved!

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