CHMP backs Europe’s first allogeneic stem cell therapy

Belgian biotech TiGenix and partner Takeda have had their stem cell therapy for perianal fistulas in Crohn’s disease patients recommended for approval in the EU.

The Committee for Medicinal Products for Human Use (CHMP) backed the allogeneic (donor) stem cell therapy – Cx601 (darvadstrocel) – as a new therapeutic option for patients who do not respond to current available therapies and face numerous invasive surgeries to correct the debilitating condition.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract affecting some 1.6 million people in Europe, and in around a quarter of patients can cause fistulas - abnormal channels connecting the bowel to another organ or the outside surface of the body.

Perianal fistulas are the most common type, linking the bowel to the skin near the anus, but are still relatively rare, so Cx601 is classed as an orphan drug, to be used in patients who don’t respond to other therapies such as antibiotics, immunosuppressant drugs and TNF blockers.

The advanced therapy medicinal product (ATMP) is the tenth in the category to be approved by the CHMP and is based on locally-administered adipose stem cells which are given as a single injection into the site of the fistula They are designed to blocks the proliferation of lymphocytes and reduce the release of pro-inflammatory cytokines at inflammation sites.

In the main phase III trial submitted in support of Cx601’s approval, the therapy was associated with a higher rate of complete remission of fistulas than placebo (50% versus 34%) after 24 weeks, and maintained long-term remission for more than a year with a lower rate of relapse than in the control group.

“Although there is a moderate difference between the treatment groups, the effect is considered to be clinically meaningful when other treatment options for fistulas have failed,” said the CHMP in its commentary on the positive opinion.

The most common side effects observed include anal abscess and fistula, as well as procedural pain and proctalgia (anal pain), said the CHMP.

TiGenix’s vice president regulatory affairs, María Pascual, said this first approval recommendation or an allogeneic stem cell therapy in Europe “reflects the maturity of our technology and its potential to offer new approaches for difficult to treat conditions”.

Along with Cx601, TiGenix has another adipose stem cell product (Cx611) in phase II trials for severe sepsis and a cardiac stem cell preparation (AlloCSC-01) heading for phase III in acute myocardial infarction.

Takeda paid €25m upfront for rights to Cx601 for this indication outside the US, pledging another €355m in milestone payments, including €15m on approval by the EMA. With a CHMP green light, that should be forthcoming early in 2018, giving Takeda a chance to add Cx601 to its existing inflammatory bowel disease portfolio headed by Entyvio (vedolizumab).

The development of the therapy in the US is running a little behind Europe, with a phase III trial getting under in the latter half of this year. TiGenix still owns the US rights to Cx601, considered a larger market opportunity for the therapy than Europe.