Alofisel withdrawn from the EU market

13 December 2024

Benefit of medicine used in Crohn’s disease no longer demonstrated

Data from a recent study have shown that Alofisel, a medicine used to treat complex anal fistulas (abnormal passages between the lower parts of the gut and the skin near the anus) in adults with Crohn’s disease, does not work well enough. The available data indicate that the benefit of Alofisel is no longer demonstrated and therefore it would not outweigh the risks associated with its use.

When Alofisel was first authorised in 2018, its benefit was considered modest and the company was asked to provide the final results of another, larger study (ADMIRE-CD II). This study, which was assessed by the CAT (EMA’s committee for advanced therapies), failed to demonstrate that Alofisel is more effective than placebo (a dummy treatment) at treating complex anal fistulas in adults with Crohn’s disease. The safety profile of Alofisel in the ADMIRE-CD II study was consistent with previous studies; the CAT noted that there are risks associated with the medicine, however no new safety signals were identified in the latest study. Data from other supportive studies were also submitted by the company.

The available data were considered insufficient to confirm the benefits of Alofisel. As the company that markets Alofisel considered that it was not possible for them to provide additional data on the effectiveness of the medicine as expected by EMA, it has decided to withdraw the medicine from the European Union (EU) market.

Information for patients

• Data from a recent study have shown that Alofisel is no better than placebo (a dummy treatment) at treating complex anal fistulas in patients with Crohn’s disease (an inflammatory condition of the gut). Fistulas are abnormal passages between the lower parts of the gut and the skin near the anus.
• The study did not raise new safety concerns with Alofisel.
• The company that markets Alofisel was not able to provide additional data on the effectiveness of Alofisel as expected by EMA, and it therefore decided to withdraw the medicine from the EU market.
• No new patients should be treated with Alofisel after 13 December 2024. If you are scheduled to receive Alofisel, you should speak to your doctor about this withdrawal and what it means for you and your treatment.

Information for healthcare professionals

• The recent study ADMIRE-CD II, a randomised placebo-controlled study investigating a single administration of Alofisel for the treatment of complex perianal fistulas in 568 patients with Crohn's disease, did not meet its primary endpoint of combined remission at 24 weeks (48.76% in Alofisel arm vs 46.32% in placebo arm, treatment difference 2.37%, p=0.571) or any of its secondary endpoints.
• The safety profile of Alofisel in ADMIRE CD-II was consihttps://www.ema.europa.eu/en/medicines/dhpc/alofiselstent with previous studies, with no new, emerging safety signals identified.
• The available data indicate that the clinical benefit of Alofisel is no longer demonstrated and therefore it would not outweigh the risks associated with its use.
• The company that markets Alofisel has therefore decided to withdraw the medicine from the EU market. In its letter to the Agency, the company stated that it was not possible for them to provide additional data on the effectiveness of Alofisel, as expected by the EMA.
• No new patients should be treated with Alofisel after 13 December 2024.

A direct healthcare professional communication (DHPC) will be sent shortly to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC will also be published on a dedicated page on the EMA website.

More about the medicine

Alofisel is a medicine for treating complex anal fistulas in adults with Crohn’s disease (an inflammatory condition of the gut) when a conventional or biological medicine has not worked well enough. Fistulas are abnormal passages between the lower parts of the gut and the skin near the anus. Complex fistulas are those with several abnormal passages and openings, or with passages that go deep inside the body, or where there are other complications such as collection of pus.

Alofisel contains the active substance darvadstrocel, which comprises mesenchymal stem cells removed from fat tissue of adult donors. It is a type of advanced therapy medicine called a ‘stem cell therapy product’.

More about the procedure

Data from study ADMIRE-CD II were assessed in the context of an application for a type II variation to the marketing authorisation of Alofisel, submitted to comply with an obligation to provide the final results of the study by mid-2024. The assessment was carried out by EMA’s Committee for Advanced Therapies (CAT), responsible for questions concerning advanced therapy medicinal products (ATMPs) for human use.

The application was withdrawn after the CAT had evaluated the information provided by the company and had prepared questions for the company. After the Committee had assessed the company’s responses to the questions, there were still some unresolved issues. As the company considered that it was not possible for them to provide additional data on the effectiveness of Alofisel as expected by EMA, they withdrew their application for the type II variation. The company subsequently communicated to the European Commission their intention to withdraw the marketing authorisation for Alofisel in the EU.

Once the European Commission has issued its final decision on the withdrawal of the marketing authorisation, Alofisel will no longer be authorised in the EU.