OCALIVA (obeticholic acid) – New Contraindication for the Treatment of Primary Biliary Cholangitis (PBC)

OCALIVA received a Notice of Compliance with Conditions in May 2017 for the treatment of PBC, pending the results of trials to verify its clinical benefit.

OCALIVA is now contraindicated for PBC patients with advanced disease, such as those with Child-Pugh Class B or C decompensated cirrhosis or a prior decompensation event, as well as for patients with compensated cirrhosis who have evidence of portal hypertension. This change is based on the frailty of and the inability to complete studies to verify its clinical benefits in these patients, as well as available safety data from post-marketing reports.

 

Audience

Healthcare professionals who specialize in the care of patients with liver disease including hepatologists, gastroenterologists and internal medicine physicians, in addition to pharmacists.

 

Key messages

• OCALIVA received a Notice of Compliance with Conditions in May 2017 for the treatment of primary biliary cholangitis (PBC), pending the results of trials to verify its clinical benefit.
• Clinical studies were not able to confirm the efficacy and safety of OCALIVA in PBC patients with decompensated cirrhosis. In addition, cases of hepatobiliary disorders, including hepatic failure and hepatic cirrhosis, have been reported in PBC patients treated with OCALIVA.
• As a result, OCALIVA is now contraindicated in PBC patients with:
  • decompensated cirrhosis (including Child-Pugh Class B or C) or a prior decompensation event;
  • compensated cirrhosis who have evidence of portal hypertension.
• The Canadian Product Monograph (CPM) for OCALIVA has been updated to reflect the new contraindication and to include additional warnings based on newly available safety data.

 

Background information

OCALIVA (obeticholic acid) is a farnesoid X receptor (FXR) agonist and a modified bile acid. It received a Notice of Compliance with Conditions in May 2017, pending the results of trials to verify its clinical benefit, for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.

The independent data monitoring committee reviewed interim data from the studies designed to confirm efficacy and safety in PBC patients with decompensated cirrhosis (moderate to severe hepatic impairment [study 747-401]) and in a broader PBC population (study 747-302). The committee determined that the studies were highly unlikely to produce any useful results, and recommended the termination of Study 747-401 and that Study 747-302 stop enrolling subjects.

In addition, there have been post-market reports of hepatobiliary disorders, including hepatic failure and hepatic cirrhosis, for which there is a possibility of a causal association with OCALIVA treatment in PBC patients with cirrhosis.

Given the difficulties completing the studies, the limited information available to further inform benefit/risk, the frailty of patients with PBC and decompensated cirrhosis, and available safety data from post-market reports, OCALIVA is now contraindicated for these patients, as well as for patients with compensated cirrhosis who have evidence of portal hypertension. The CPM for OCALIVA has been updated to include the new contraindication and additional warnings based on newly available safety data.

In Canada, OCALIVA is distributed principally through the Navigate Patient Support Program (PSP). Healthcare professionals can contact their Advanz Pharma Canada Inc. (formerly Intercept Pharma Canada Inc.) representative or the Navigate PSP for more information.

 

Information for consumers

OCALIVA is used to treat primary biliary cholangitis (PBC) in adults. PBC is a disease of the liver causing destruction of the bile ducts, which are part of the digestive system. Bile ducts are thin tubes that carry bile from the liver and gallbladder to the small intestine.

OCALIVA decreases the production of bile acids in the liver and increases the removal of bile from the liver. This may slow or prevent progression of the disease.

OCALIVA was authorized with conditions based on promising evidence of clinical effectiveness following review by Health Canada. The manufacturer agreed to complete more studies to ensure that the drug works the way it should.

Since the manufacturer is not able to complete certain studies and given that there are reported cases of liver injury, OCALIVA is no longer approved to be used for patients who have:

• late-stage liver cirrhosis (decompensated cirrhosis), or who have previously experienced a decompensation event;
• liver cirrhosis (compensated cirrhosis) and show signs of portal hypertension (high blood pressure in the veins in the liver), such as water accumulation in the abdomen or enlarged veins in the esophagus.

Patients should contact their healthcare professional immediately if they develop symptoms of worsening liver injury, such as swelling of the abdomen-area from a build-up of fluid, yellowing of the skin or the whites of the eyes, blood in the stool, coughing or vomiting blood, confusion, drowsiness, and slurred speech. Patients should discuss any questions or concerns about this information with their healthcare professional, or their Navigate Patient Support Program case manager.

 

Information for healthcare professionals

OCALIVA is now contraindicated in PBC patients with:

• decompensated cirrhosis (including Child-Pugh Class B or C) or a prior decompensation event;
• compensated cirrhosis who have evidence of portal hypertension.

Healthcare professionals are advised of the following:

• Do not start treatment with OCALIVA in patients who have decompensated cirrhosis (including Child-Pugh Class B or C) or who have had a prior decompensation event, or in patients who have compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia).
• Discontinue treatment with OCALIVA in PBC patients with decompensated cirrhosis, and in patients with compensated cirrhosis who have evidence of portal hypertension.
• Routinely monitor patients during OCALIVA treatment for progression of PBC. Treatment with OCALIVA should be permanently discontinued in patients with laboratory or clinical evidence of hepatic decompensation, including progression to Child-Pugh class B or C, or in patients who have compensated cirrhosis and develop evidence of portal hypertension.

 

Action taken by Health Canada

Health Canada has authorized the updated CPM for OCALIVA.

Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication update will be further distributed through the MedEffect™ e-Notice email notification system, as well as through social media channels, including LinkedIn and Twitter.

 

Report health or safety concerns

Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Any case of serious or unexpected side effects in patients receiving OCALIVA should be reported to Advanz Pharma Canada Inc. or Health Canada.

 

Advanz Pharma Canada Inc.

4263 Sherwoodtowne Blvd., Suite 300

Mississauga, ON, L4Z 1Y5

 

To correct your mailing address or fax number, contact Advanz Pharma Canada Inc.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

• Calling toll-free at 1-866-234-2345; or
• Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

 

For other health product inquiries related to this communication, contact Health Canada at:

Marketed Health Products Directorate

E-mail: mhpd-dpsc@hc-sc.gc.ca

Telephone: 613-954-6522

Fax: 613-952-7738

 

Original signed by

Brian Canestraro

Vice-President and General Manager

Advanz Pharma Canada Inc. (formerly Intercept Pharma Canada Inc.), part of the Advanz Pharma Group.