TxCell Plans 2016 U.S. Studies In Crohn’s After Addressing Manufacturing Issues
This article was originally published in The Pink Sheet Daily
Executive Summary
The French cell therapy company is planning to extend its pivotal Phase II study in Crohn’s disease to the U.S. It is one of the larger studies of a cell therapy to date, evaluating what is thought to be the only cell therapy using regulatory T-lymphocytes.
TxCell SA, the only cell therapy company believed to be exploring the therapeutic potential of regulatory T-cells (Tregs) in large-scale studies, is planning to extend its Phase IIb clinical study to the U.S. in 2016 using a recently granted IND, newly appointed CEO Stephane Boissel said.
The Valbonne, France-based firm hopes to benefit from the progress being made by other companies, including big pharma, in the cell therapy sector. Novartis AG, for example, could possibly be in a position to file a U.S. BLA for the cell therapy CTL019 in the treatment of acute lymphocytic leukemia (ALL) in 2016. “This would be the first cell therapy in a large indication to reach the BLA stage, and would give a boost to cell therapy approaches,” Boissel said in a recent interview (Also see "CAR T-cell Therapy Shines In ALL; Safety Fix Highlighted At ASH" - Pink Sheet, 8 Dec, 2014.).
That said, TxCell has to work on manufacturing issues first, announcing June 24 it was putting a partial hold on its pilot manufacturing plant in Besancon, France, to remove the possible risk of microbial contamination, following discussions with the French regulator ANSM. Such contamination has not been seen but the potential risk must be addressed. “All existing players in the field have challenges in manufacturing, but the good news is that we know how to address the issue, and the pilot plant should be GMP compliant by the first quarter of 2016,” Boissel said.
TxCell has decided to recruit a commercial manufacturing organization to be responsible for commercial supplies for its Crohn’s disease therapy from 2018 onwards.
Lead product Ovasave is being evaluated in a Phase IIb study, CATS29, in Europe, believed to be the largest trial ever conducted for a cell therapy. It involves 30 medical centers in six countries and 160 severe refractory Crohn’s disease patients and is expected to be completed in 2017. When GMP-manufactured product is available, the study will be extended to the U.S., possibly in the first half of 2016, Boissel said.
The primary endpoint is response to a single injection of 10 million cells of ovalbumin-specific Treg cells compared with placebo six weeks after administration, with a response defined as a decrease of greater than 100 points in the Crohn’s Disease Activity Index (CDAI). Patients will then receive up to three additional doses of Ovasave, or placebo.
The product is being positioned as the last option for younger patients, aged around 35 years, who have Crohn’s disease that is refractory to all other therapies including steroids, immunosuppressives and anti-TNFs, and have no medical options left. The Swiss company Trizell Holding SA and its affiliate Ferring International Center SA. have an option to fund Phase III and to commercialize Ovasave.
TxCell expects to enter the clinic next year with a second potential cell therapy Col-Treg for non-infectious uveitis, a rare autoimmune disease that is one of the main causes of blindness in developed countries, with around 30,000 patients every year in the U.S. and Europe becoming refractory to current therapies. The company plans to develop therapies for such niche indications itself but will look for development partners for products with larger patient populations.
Untapped Potential
Boissel joined the French cell therapy company at the end of April, attracted he says by the untapped potential of TxCell’s technology and the maturing nature of the sector. He most recently was CEO of Nancy, France-based Genclis SAS, a molecular diagnostics company, and before that was CFO of gene therapy pioneer Transgene SA.
“TxCell is emerging into the mainstream with a totally different approach to cell therapy from companies like Juno Therapeutics Inc. and Kite Pharma Inc., that all work in cancer with a different cell type, T-effector cells,” he noted. “We work at the other end of the spectrum; there is no other platform working specifically with regulatory T-cells, and in a non-cancer indication.”
TxCell is one of a number of European companies with cell therapy products in advanced development: Belgium’s Celyad SA (formerly Cardio3 Biosciences) has cardiac progenitor cells in Phase III for the treatment of heart failure, and recently raised $100 million in a U.S. IPO and European placing ([See Deal]). The British company ReNeuron Group PLC is developing allogeneic stem cells and has a stroke product in Phase II and a cell therapy for critical limb ischemia in Phase I; it raised £68.4 million ($106 million) in a conditional placing on July 10.
In addition to using a unique T-cell approach, TxCell has also reduced the complexity of its cell processing that allows blood to be collected once from patients and then stored frozen. In TxCell’s manufacturing process, one blood collection can be enough for up to five years of therapy, and blood does not have to be collected and processed for each dose, Boissel said.
He noted that other cell therapy companies nearing the market have developed similar processes that only require one manufacturing step. This is shown by recent news from Kite that it has the capability to manufacture its autologous T-cell therapies in six to eight days and is planning for a possible launch of its first product in 2017 (Also see "With Clinical Trial Supply Worked Out, Kite Focuses On Manufacturing Commercial Product" - Pink Sheet, 6 Jul, 2015.).
TxCell takes peripheral blood from patients and T regulatory lymphocytes are taught to recognize an antigen present in inflammatory cells in Crohn’s disease patients. A large number of primed regulatory T-cells are then produced that can be frozen and stored until needed for treatment over a number of years. The company claims to have a strong IP position protecting its work, something that’s not always true for some big players in the cell therapy field .
TxCell was spun out of the Inserm, France’s National Institute for Health and Medical Research, more than 10 years ago and raised €16.2 million ($17.8 million) in an IPO on Euronext Paris in April 2014 ([See Deal]).