On November 25, 2019, CymaBay halted all clinical trials of seladelpar after atypical histologic findings with no clinical or laboratory correlates were identified at the planned end-of treatment biopsy review of a 52-week Phase 2 NASH study. The FDA concurred with this decision and placed all active INDs for seladelpar on clinical hold. CymaBay committed to an in-depth investigation of these findings and comprehensive safety evaluation that concluded with an independent, expert panel review involving some of the world’s leading liver pathologists and hepatologists. The expert panel found no clinical, biochemical or histological evidence of seladelpar-related liver injury in the Phase 2 NASH study and unanimously supported re-initiating clinical development of seladelpar pending approval by the FDA. Based on the results of the investigation and the expert panel conclusions, FDA concluded that clinical trials for NASH, PBC and PSC may resume.
Seladelpar, a drug developed for PBC patients, has shown positive results in Phase 2 studies- normalizing ALP levels, while not associated with itching. In November with FDA breakthrough therapy designation for PBC, CymaBay announced an extended Phase 3 study. Previously, a 52 week study of Seladelpar was undertaken for NASH (Non-alcoholic steatohepatitis) patients.
Today CymaBay announced that it will be putting on hold its PBC clinical trials, while halting other trials. It is important to note that as notified publicly by CymaBay, there have not been any concerns raised in the PBC trial, but the company is acting out of an abundance of caution, and with patient safety foremost.
The company cited atypical findings observed in the study of NASH patients; while blood work (biochemical) improved, biopsies showed abnormalities in liver cells (histology). CymaBay has initiated a series of investigative actions to better understand these findings with the focus on ensuring patient safety and care and will be updating all stakeholders regularly.
We feel it’s important to make sure you are aware of this issue. If you are currently enrolled in a Seladelpar study and have any questions or concerns, you should talk to your doctor.
Seladelpar clinical trial sites
AZ: Chandler, Phoenix, Tucson
CA: Los Angeles, Stanford, UC Davis, San Francisco
CT: New Haven
FL: Boca Raton, Lakewood Ranch, Miami, Tampa
KS: Kansas City
MN: Maplewood, Minneapolis
MS: Jackson, Tupelo
MO: Kansas City
NY: NYC, Rochester
NC: Asheville, Duke
PA: Bethlehem, Hershey, Pittsburgh
TN: Germantown, Knoxville, Nashville
TX: Dallas, Ft Worth, Houston, San Antonio
VA: Newport News, Richmond
Elafibranor, phase 2 trial has shown positive preliminary results in helping those PBC patients who do not respond to UDCA (Urso). In addition, Elafibranor has recently been granted “Breakthrough Therapy Designation” by the FDA as well as “Orphan Drug Designation”. Read more.
Linerixibat (GSK2330672), a drug that is being developed for PBC patients who experience itchiness, has recently been granted “orphan” status by the FDA. This is wonderful news for patients who are suffering from itchiness (pruritus) which is one of the main symptoms of Primary Biliary Cholangitis.
Orphan status is a special designation given by the FDA for drugs that target rare diseases. With orphan status companies are encouraged to develop treatments for a rare diseases. Rare disease patients benefit from orphan status as the drug development process is shortened and treatments become available sooner.
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. Read more about this study here.
Genkyotex “published interim efficacy results today, GKT831 met both it’s primary and secondary endpoints in the Phase II PBC trial! A big thank you to the patients who participate in the study and their doctors. And congrats to the Genkyotex team.” Read results here.
Novartis has cancelled its phase II trial for a non-bile acid FXR agonist in patients with PBC.
More exciting news for PBC patients and their families. Arena Pharmaceutical is beginning a proof of concept clinical trial in Australia and New Zealand for Etrasimod. Read more.
Phase 2 trial is now enrolling patients in 50 centers involving 102 patients worldwide. This is a 24 week long study involving 8 clinic visits. Principal Investigators in Canada: Dr. Catherine Vincent, Montreal; Dr. Giada Sebastiani, Montreal Dr. Mark Swain, Calgary; Dr. Gerald Minuk, Winnipeg. More details about the trial here.