TiGenix received a European Medicines Agency (EMA) recommendation for the marketing authorization of Alofisel (darvadstrocel, Cx601) as an advanced therapy medicinal product (ATMP) for the treatment of complex perianal fistulas in people with Crohn’s disease.
Perianal fistulas occur when an abnormal opening develops between the rectum and the outside of the body. It can lead to incontinence and sepsis (infection in the blood). In Crohn’s disease, perianal fistulas develop as a consequence of patients’ inflammatory bowel disease.
The active substance in Alofisel, darvadstrocel, contains expanded adipose stem cells that impair proliferation of lymphocytes (immune system cells) and reduce the release of pro-inflammatory molecules at inflammation sites. This immuno-regulatory activity resolves inflammation and allows the tissues around the fistula tract to heal.
The marketing authorization recommendation follows the results of the Phase 3 ADMIRE-CD clinical trial (NCT01541579) involving 278 participants. After a 24-week treatment, 49.5 percent of the patients who received Alofisel were in remission, compared to one-third of the patients receiving placebo. An extended 104-week ongoing follow-up study so far supports this achievement.
The effect is considered clinically meaningful because other treatment options for fistulas have failed so far, as there is only a moderate difference between treatment groups. Side effects observed included anal abscess and fistula, as well as procedural pain and proctalgia.
The EMA granted orphan drug status to Alofisel, meaning the drug could eventually receive 10 years of exclusivity in the European market, if the status is maintained after new data is revised.
This is the 10th ATMP to receive a positive opinion from EMA’s Committee for Medicinal Products for Human Use (CHMP). It is an intermediary step on the drug’s path to approval before patients can access a new drug. Once a marketing authorization is granted, price and reimbursement is decided at the national level, depending on the importance the medicine can potentially take in each context.
In October 2017, TiGenix announced the U.S. Food and Drug Administration (FDA) awarded orphan drug status to Cx601, the developer’s drug name before it was given its trade name of Alofisel.
TiGenix is now recruiting for a global Phase 3 clinical trial (NCT03279081) likely to yield additional clinical data to support the filing of a Biologics License Application (BLA) with the FDA for Cx601. The ADMIRE-CD II trial is a randomized, placebo-controlled study that aims to enroll 326 Crohn’s patients with perianal fistulas that have not adequately responded to prior lines of treatment.
The EMA’s opinion will now be sent to the European Commission for its decision for an EU-wide marketing authorization.