BioWorld International Correspondent

Italian gene therapy pioneer MolMed SpA is moving its cell therapy for improving the outcome of hematopoietic stem cell transplants from partially compatible donors into a Phase III clinical trial in Italy, following its recent receipt of approval from the Rome-based Italian Medicines Agency AIFA.

Fully compatible donors only can be found for about 40 percent of patients with bloodborne malignancies, such as leukemia and lymphoma, who need hematopoietic stem cell transplants. Graft-vs.-host disease (GvHD), in which transplanted immune cells attack host tissue, is a major and sometime fatal complication in transplants of partially matched stem cells.

MolMed's TK therapy is designed to reduce the risk of GvHD, and thereby improve patient survival and widen the pool of potentially suitable donors.

In hematopoietic stem cell transplant protocols, transplanted donor T-cells are important in providing graft-vs.-leukemia activity and in providing resistance against infection before the host's immune system can be reconstituted by the transplanted bone marrow stem cells. They also eliminate the need for immunosuppressive therapy. However, because of the risk of GvHD, current protocols often involve T-cell depletion of the graft and the administration of immunosuppressive drugs.

MolMed's approach to preventing GvHD involves the ex vivo genetic engineering of donor lymphocytes to express a suicide gene - herpes simplex virus (HSV) thymidine kinase - that can be triggered should the condition arise.

Administration of the common antiviral drug ganciclovir kills off actively dividing T cells, including those that are mounting an inappropriate immune attack. "You eliminate only those T cells that are active," MolMed business development manager Holger Neecke told BioWorld International.

In a Phase I/II clinical trial of the therapy, 10 out of 22 patients who experienced immune reconstitution required the intervention, he said. The upcoming trial will recruit 200 patients in 10 to 15 centers located in Italy and in several other countries, including, potentially, the UK, Germany, Greece and Spain. The study will take three to four years to complete, Neecke said.

The company's primary focus will be on patients with acute myeloid leukemia, as that patient group exhibited the best response during the earlier study, which had recruited a total of 50 patients in all.

The company, which is located in the San Raffaele Science Park in Milan, is not expecting to launch the product before 2012. "It might be earlier if we get a conditional approval, but we're playing it safe," Neecke said.

As it is a niche product that can be sold via a limited number of bone marrow transplant centers, MolMed will commercialize it itself. It also plans to commence clinical development of the therapy in the U.S. this year.

The initial study will be managed by the M.D. Anderson Cancer Center in Houston.