CymaBay – Seladelpar – re-initiating Phase 3 clinical trial for PBC

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.

CymaBay puts PBC Seladelpar Clinical Trials on hold

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
CO: Denver
CT: New Haven
FL: Boca Raton, Lakewood Ranch, Miami, Tampa
GA: Atlanta
IL: Chicago
IN: Indianapolis
KS: Kansas City
LA: Tulane
MA: Boston
MI: Novi
MN: Maplewood, Minneapolis
MS: Jackson, Tupelo
MO: Kansas City
NY: NYC, Rochester
NC: Asheville, Duke
OH: Cleveland
PA: Bethlehem, Hershey, Pittsburgh
TN: Germantown, Knoxville, Nashville
TX: Dallas, Ft Worth, Houston, San Antonio
UT: Murray
VA: Newport News, Richmond
WA: Seattle
AB: Calgary
ON: Toronto
QC: Montreal
MB: Winnipeg 

Linerixibat (GSK2330672) granted Orphan Status

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.

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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.