Clinical Trials

Date: 2014-02-26

Type of information: Results

phase: 1b

Announcement: results

Company: Fate Therapeutics (USA - CA)

Product: Prohema® (16, 16-dimethyl prostaglandin E2, or dmPGE2, modulated cord blood)

Action mechanism:

• stem cell therapy. Prohema® is a pharmacologically-modulated, cord blood-derived hematopoietic stem cell (HSC) therapeutic. Prohema® is produced through a proprietary, two-hour, ex vivo cell modulation process that results in rapid activation of key biological pathways involved in homing, proliferation and survival of HSCs. In preclinical testing, PROHEMA® has demonstrated the potential to accelerate engraftment and to drive durable hematopoietic reconstitution, without the need for multi-week expansion protocols. In an initial Phase 1b study in adult patients with hematologic malignancies undergoing double umbilical cord blood transplant (dUCBT), the median time to neutrophil recovery ( > 500 cells/µL) with Prohema® was 17.5 days, which compares favorably to historical norms for patients undergoing dUCBT. In that study, 100-day survival with Prohema® was 100%, and Prohema® provided the dominant source of hematopoiesis in 10 of 12 evaluable subjects, suggesting that treatment with Prohema® may accelerate engraftment and drive durable and preferential reconstitution.

Disease: adult patients undergoing hematopoietic stem cell (HSC) transplantation for hematologic malignancy

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On February 26, 2014, Fate Therapeutics, a biopharmaceutical company engaged in the discovery and development of adult stem cell modulators to treat orphan diseases, announced the release of new data on the observed effects of ex vivo pharmacologic modulation on CD8+ T cells and immune reconstitution from its previously-completed Phase 1b clinical trial of Prohema® (16, 16-dimethyl prostaglandin E2, or dmPGE2, modulated cord blood) in adult patients undergoing hematopoietic stem cell (HSC) transplantation for hematologic malignancy (the ProHema-01 trial). Researchers affiliated with Harvard Medical School performed an analysis of the CD8+ T cell compartment using patient samples from the ProHema-01 trial. At Day 100, subjects who received Prohema® and an unmanipulated cord blood unit (n=12) showed a two-fold increase in the percentage of naïve and early memory T cell fraction within the CD8+ T cell compartment as compared to subjects who received two unmanipulated cord blood units (n=9). These naïve and early memory CD8+ T cell populations are believed to play a key role in promoting immune reconstitution and viral immunity following cord blood transplantation. These findings were recently published in Blood Cancer Journal (Li, L. et. al. Blood Cancer Journal 2014). "In addition to the well-established effect of dmPGE2 on enhancing the engraftment properties of hematopoietic stem cells, our molecular characterization and immunological assessments provide new evidence that dmPGE2 can also significantly improve the functional properties of T cells contained within human umbilical cord blood, stated Dr. Vicki Boussiotis, M.D., Ph.D., Professor, Department of Medicine, Harvard Medical School, and senior author on the Blood Cancer Journal publication. "Enhancing the survival and immunological properties of T cells, and in particular those of naïve CD8+ T cells, may have significant therapeutic implications for harnessing immune memory in the context of both pathogen- and tumor-specific immunity." Consistent with these reported immunomodulatory effects, low rates of viral reactivation were observed in the ProHema-01 trial. Specifically, cytomegalovirus (CMV) reactivation occurred in only two of 12 Prohema® subjects (17%), with no cases of CMV disease. In addition, no cases of Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) were observed. These observations compare favorably to rates of CMV reactivation and EBV-associated PTLD reported in the literature of 36-56% and up to 16%, respectively. "The functional properties of both hematopoietic stem cells and T cells are critical determinants of patient outcomes following allogeneic umbilical cord blood transplantation," commented Pratik Multani, M.D., M.S., Chief Medical Officer of Fate Therapeutics. "These novel scientific and clinical observations raise the possibility that T cell-related mechanisms may also be enhanced using ex vivo pharmacologic modulation strategies. We look forward to evaluating patient outcomes related to dmPGE2-mediated immunomodulatory effects in our planned Phase 2 clinical trial of Prohema®."
• Prohema® is currently in clinical development for use in adult patients with hematologic malignancies undergoing double umbilical cord blood transplantation.Following an optimization of the Prohema® manufacturing process, the Company expects to resume enrollment of its Phase 2 clinical trial (the ProHema-03 Trial) in the first half of 2014, with the goal of generating full data on the primary and major secondary endpoints related to engraftment in mid-2015.

Is general: Yes