This article is more than 5 years old. Information may no longer be current.
Trabedersen granted orphan drug status for pancreatic carcinoma
The investigational drug trabedersen has been granted orphan drug designation by the FDA and the European Medicines Agency for the treatment of pancreatic carcinoma.
Trabedersen (Antisense Pharma) is a first-in-class, targeted, antisense compound designed to down regulate the production of the protein transforming growth factor-beta 2 at the translational level.
The orphan drug designation is based on data from an ongoing phase-1/2 study in which the drug has shown a good safety profile, and encouraging survival data in patients with advanced pancreatic carcinoma. The trial has enrolled 23 patients. Patients are assigned to trabedersen as second-, third-, or fourth-line treatment either in a seven-day on/seven-day off or four-day on/10-day off schedule.
As of August 2009, the median OS for patients on the first schedule was 6.8 months. One patient with recurrent advanced cancer with liver metastases on this schedule had a complete response and is still alive at 45.6 months.
The first cohort assigned the second schedule included five patients. The median OS for these patients was 13.4 months. One patient is still alive at 19 months.
Trabedersen was given orphan drug status for the treatment of high-grade gliomas in 2002.
Trabedersen is a first-in-class molecule that targets a signaling pathway — TGF-beta — that has yet to be fully exploited from a cancer therapeutic standpoint. The primary reason for this has to do with the pleiotropic effects of TGF-beta signaling, with its ability to act as both tumor suppressor and tumor promoter at different stages of tumor progression. Obviously, this raises concerns about the effects that such a targeted agent might have in terms of potentially accelerating cancer growth. Nonetheless, this agent has shown intriguing results in an early (phase-1/2) study that was enriched for patients with advanced pancreatic cancer resistant to standard therapies, with several such patients showing prolonged survival and disease control. In addition to its unique target, trabedersen acts differently than the monoclonal antibodies and small-molecule inhibitors that we have become familiar with that have made it to clinic: namely, it is an antisense oligonucleotide, meaning that it acts by binding to its target mRNA (in this case, TGF-beta 2) to prevent gene translation. With both its focus on a new, underexplored pathway and its different mechanism of action, trabedersen is certainly worthy of further exploration. However, if history serves as our guide, given the limited success with other targeted agents in pancreatic cancer (targeting EGFR, VEGF, KRAS, amongst others) and the unfortunate fact that favorable results in small phase-1/2 trials in pancreatic cancer have rarely been duplicated in larger-scale phase-2 or -3 studies, we should be tempered in our enthusiasm and wait until more evidence of its efficacy and safety becomes available.
– Andrew H. Ko, MD
HemOnc Today Editorial Board member
