I am signing this letter as a patient with primary biliary cholangitis (PBC), or as a representative of the PBC community, who is concerned about the potential threat to the development and approval of new drugs in this condition. PBC patients completely understand the need for any new treatments to be both safe and effective. We as patients are the people who have most to gain. As a community we have shown our commitment to research in the condition by participating in trials and other forms of research that have contributed to real progress. We are very grateful for this progress, but are concerned about the risk that it goes into reverse. In deciding on the future of drugs we respectfully request that regulators see and understand the challenges from the perspective of us as patients. To be told that we are high risk of dying of the disease or needing a transplant and then to request that, on this basis, we take part in a long term trial with a placebo arm whilst the drug that we have seen to be effective, in fellow patients, on the key blood tests that we are told to monitor as they show the severity of disease and its response to treatment, is to put us and our families in an impossible position. I and my fellow patients simply ask that you understand the impossibility of that position and look at other ways to get the evidence of effectiveness and safety that you need. We, as a community, would, as we have always done, support the search for that evidence.

When Obeticholic Acid was granted a conditional licence, it was agreed that there should be a confirmatory trial (with a placebo arm), even though Obeticholic Acid (OCA) was now available. This trial was known as COBALT.

The COBALT trial was deemed a failure as it was unable to answer the questions set. Many patients on discovering they were on the placebo arm actively sought treatment through their physician. We are now aware this COBALT created some remarkable results, including the highest positive result in any placebo arm in the entire history of PBC trials. We, the patients, would respectfully ask regulators and pharmaceutical companies to ensure they are asking the best possible questions, in order to gain the best possible answers. We humbly suggest a placebo arm trial in an approved, albeit conditionally, therapy is not the best question to ask.

We would like to highlight that, in our view, OCA is an important part of a clinician’s therapeutic toolkit in PBC, and that we see potential benefit and accept potential risk. It takes many years to prove that a therapy works and is safe over many years. It took years to prove UDCA works for PBC patients, and we are prepared to wait those years to prove OCA is also of benefit, based upon current real world evidence available.

We continue to support efforts to bring better therapies in PBC, and hope that our experience, lived challenge, and view is part of that effort.