This blog was last updated on 19th December 2024 (see below)
On 28th June 2024 the European Medicines Agency (EMA) announced that they were recommending that obeticholic acid (OCA), brand name Ocaliva, be taken off the market in the EU.
OCA is a treatment for primary biliary cholangitis (PBC), a disease of the bile ducts that can lead to liver damage and cirrhosis. It is used for patients who can’t have the main treatment, ursodeoxycholic acid (URSO), or in whom URSO doesn’t work.
People taking or considering OCA will understandably be worried and have questions. This blog has the answers to the main questions and we will keep it updated. If you are worried, you should speak to your liver team.
Update December 2024
On 12th December 2024 the US Food and Drug Administration (FDA) issued a drug safety communication about obeticholic acid. It highlights new research that shows a possible link between obeticholic acid and liver damage. It was already known that obeticholic acid could cause liver problems in people with advanced cirrhosis – so they should not be given it. The new information suggests there could also be a risk for a small number of people who do not have cirrhosis.
Obeticholic acid has not been withdrawn in the US. The FDA advises doctors to make sure they are following prescribing rules for obeticholic acid and to keep a close eye on patients taking it with regular check-ups. The FDA will keep monitoring the situation.
This is different to the EU licensing issue that is the main topic of this page. The trial that led to the EU withdrawing obeticholic acid’s license there found no new safety issues. The UK’s Medicines and Healthcare products Regulatory Agency has not made any announcements about either the EU licence withdrawal or the FDA communication.
If you are worried, speak to your medical team. It’s important to keep taking your medicines as prescribed. Do not stop or reduce them without talking to your doctor.
Update November 2024
On November 27th, 2024 the suspension granted in September was lifted. This means that the original decision to revoke the licence in the EU is in effect. This does not affect the UK.
Update September 2024
On September 5th, 2024, the decision to take OCA off the market in the EU was suspended. This means that OCA will be available to current and new patients in Europe.
The decision was made by the General Court of the European Union. It does not change how OCA is used in the UK. Doctors will continue to be able to prescribe OCA here.
Can I still take OCA?
Yes.
The first thing to say is that the EMA does not apply to the UK. Medicines in this country are licenced by the Medicines and Healthcare Products Regulatory Agency (MHRA). You should continue to take OCA as usual. Doctors can still start eligible patients on OCA.
Tim Cross, Consultant Hepatologist at the Royal Liverpool Hospital, says “The main thing is not to panic. At the moment, nothing has changed in the UK. And there are no new safety issues. So patients should continue to take OCA and doctors can still prescribe it. Speak to your liver team if you have questions or concerns.”
Will there be a review in the UK?
We don’t know yet.
The MHRA have not said yet whether they will also review OCA. If they do, nothing will change while the review happens. This usually takes several months. It will include getting the views of clinicians, scientists and patients, including the British Liver Trust.
Is OCA still safe to take?
Yes.
When doctors prescribe OCA they check that it will be safe for you to take. This includes checking for anything that might mean you can’t take it or need to take a different amount. For the first few months, they also check that it is working and not causing any worrying side effects.
The EMA had no concerns about the safety of OCA.
If you are worried about side effects or whether OCA is safe for you, speak to your clinical team. Never stop or reduce your medicine without speaking to your doctor.
Why do the EMA want to withdraw OCA?
This is complicated and to do with the licencing process.
When the EMA approved a licence for OCA there were some conditions. This was because the licence was given before the trials were fully finished. The signs were good that OCA could help patients, and the EMA wanted to give people the chance of a treatment.
The full trial, called COBALT, has finished now. But instead of showing how well OCA works, as expected, it isn’t clear cut. The trial shows no difference between OCA and a dummy drug (placebo). But, and this is a big but, the trial had to be stopped early because there weren’t enough people taking part. This means we can’t rely on the results.
The EMA licence said the final trial had to show OCA worked well. Because the trial did not show this, they have recommended it is withdrawn.
There is likely to be an appeal against the EMA’s recommendation in the European Union (EU). Other studies have suggested longer term benefits of OCA, so it’s a grey area.
What have the trials of OCA shown and how has that fed into the licence process?
Both the EMA and the MHRA gave OCA a conditional licence. The decisions to licence OCA were made because of evidence showing OCA can bring markers of liver damage, like ALP (alkaline phosphatase) and bile acids, back in range.
But the trial hadn’t gone on long enough to show OCA stopped people from dying or needing a liver transplant. A longer trial called COBALT would investigate this. The regulators said they would wait for the results of COBALT to make a final decision.
The COBALT trial has now produced a result, which doesn’t show OCA helps reduce deaths or transplants. But the trial had problems getting enough people to take part and then keeping them in the trial. A key reason for this was because, once OCA was available, people understandably didn’t want to take the chance of being given a dummy drug (placebo).
Trials can only show their results are not down to chance if they have enough people. So scientifically, the result of the trial is not reliable. It is very possible that the result is because the study didn’t have enough people, not because OCA doesn’t help people with PBC.
It’s a bit like searching for gold. There are signs that a field might have gold underneath, so you dig a hole to see if you can find it. But if you don’t dig a big enough hole, you don’t know if there’s no gold there to find. Or if you just didn’t look hard enough.
Does this mean OCA cannot help people with PBC?
No. The COBALT result can’t say for sure if OCA helps stop people dying from PBC.
Many doctors and scientists, including the British Association for the Study of the Liver (BASL) and the British Society of Gastroenterologists (BSG), have expressed concerns with the EMA’s decision. They believe that OCA helps patients and want to keep prescribing it.
There are the original trial results showing that OCA can improve the blood levels of ALP and bile salts. And there is now evidence from people taking OCA on prescription, rather than as part of a clinical trial. In 2023 a UK-wide study showed OCA can reduce ALP levels and help people normalise blood levels of other markers for liver damage.
A global study, including many UK patients, compared people taking OCA as part of a trial with people outside the trial who weren’t taking it. The results showed that the people taking OCA were less likely to die or have a liver transplant.
These new results aren’t enough to be sure OCA works as well as we hope. But they are encouraging.
Dr Neil Halliday, Consultant Hepatologist at the Royal Free Hospital London, explains “the COBALT results mean there’s a grey area – but that was already the case. Looking at all the evidence, and listening to the experiences of my patients, OCA is still an important drug for treating PBC.”
What will happen next?
In the EU, the EMA’s recommendation needs to be agreed. There is likely to be an appeal, so there might not be a final decision for some time.
In the UK, there is no change to what doctors or patients need to do. The liver community will have to wait to see what the MHRA decide to do.
This decision has raised a lot of questions about how licencing works in the UK and elsewhere. At the time it seemed sensible to wait for all the results before making a final decision. In reality, it’s hard to carry out reliable studies when a medicine is available. Patients need to manage their condition and get on with their lives.
The British Liver Trust and Children’s Liver Disease Foundation work hard to make sure patients’ voices are heard when it comes to decisions about treatment. And we will make sure your views are represented whatever happens next.
If patients or relatives have any concerns you should contact your clinical team.
