LONDON – TiGenix NV unveiled positive Phase IIa results for its Cx611 allogeneic stem cell therapy in the treatment of 53 rheumatoid arthritis patients whose disease was not responsive to disease-modifying anti-rheumatic drugs (DMARDS) or biologics.

"This is an extremely tough patient population, and was [to my knowledge] the most refractory rheumatoid arthritis patient group ever in a rheumatoid arthritis trial," said CEO Eduardo Bravo.

"You will appreciate how happy we are to report these results [which] give the first ever sign of clinical benefit [from stem cell therapy] in rheumatoid arthritis," he told a teleconference held to discuss the trial data.

Although the Phase IIa was designed as a safety and dose-ranging study, TiGenix was looking for – and found – evidence of efficacy, with five patients reported as being in remission according to the standardized assessment DAS28 (Disease Activity Score) at the final (six-month) follow-up.

Cx611 is the most advanced stem cell therapy in development of the treatment of rheumatoid arthritis currently.

In terms of safety, one patient suffered a serious adverse event that led to discontinuation of treatment.

All other side effects were mild and transient, with no signs of any impact on any hematological parameters or any thrombosis. The trial indicated that the lowest of three doses tested (1 million, 2 million and 4 million cells per kilogram), "seems to be enough" Bravo said.

At six months, patients treated with Cx611 showed improvements against the placebo arm in the standard American College of Rheumatologists assessments of ACR 20, ACR 50 and ACR 70, and in EULAR (European League Against Rheumatism) and DAS28 assessments.

The data gave an overview of the results, and Bravo said a more detailed analysis now is in progress.

"We have a wealth of good data for future development in rheumatoid arthritis and other autoimmune diseases," he said.

Bravo refused to be drawn at this juncture on how Leuven, Belgium-based TiGenix plans to proceed with development, or how future trials will be financed. The main options are to take Cx611 forward into a Phase IIb trial in refractory rheumatoid arthritis, do a Phase IIb in a less-difficult-to-treat rheumatoid arthritis population, or to segue into a study in lupus or another autoimmune disease where it would be possible to get orphan drug status.

"We won't say at this stage if we are going for the tougher-to-treat population or [patients] more upstream. There are still decisions to be made," Bravo said. TiGenix is in the process of forming an international advisory board, and Bravo said the data will be referred to this board before deciding on the route to market.

Similarly, Bravo declined to discuss in any detail how any trial would be financed, saying only that it could be from existing funds, alternative financing sources, soft loans, capital markets or partnering. TiGenix had €11.1 million (US$14.4 million) cash at the end of 2012. The typical size of a Phase IIb in rheumatoid arthritis is 250 patients.

Bravo said that at present TiGenix is not actively looking to partner Cx611, which consists of allogeneic stem cells derived from adipose tissue,

The company has said, however, that it wants to partner the same allogeneic stem cells in the treatment of complex perianal fistulas caused by Crohn's disease.

That product, Cx601 is currently in a pivotal Phase III trial with results expected in the first half of 2014.

The mean time since diagnosis of rheumatoid arthritis in the 53 patients in the Cx611 Phase IIa trial was 15 years. In terms of previous treatments, the mean was that they had received three DMARDs and three or more different biologic drugs.

"The patients had gone through a number of biologics before they were treated with stem cells," Bravo said, noting that the treatments not only included anti-TNF alpha, but also other families of biologic drugs.

More than 50 percent of rheumatoid arthritis patients move on from a first biologic to others, either due to an inadequate response or adverse events.

According to TiGenix, at any point in time 5 percent to 10 percent of rheumatoid arthritis patients will have failed on biologics, a combined population in the U.S., Europe and Japan of 150,000 to 300,000 patients.