Rexin-G® - Tumor-Targeted Injectable Genetic Medicine
About Rexin-G®
Scientists at Epeius Biotechnologies have developed the high-technologies that can deliver a new class of powerful biological agents directly to tumors that have spread throughout the body (metastatic cancer). The lead product, Rexin-G, is a sophisticated gene delivery vehicle (or vector); a tumor-targeted nanoparticle that is programmed to deliver a tumor-killing designer gene precisely where it is needed most. Rexin-G has been validated in international clinical trials, where it is shown be highly active against a broad spectrum of chemo-resistant tumor types, causing tumor shrinkage in patients suffering from metastatic cancer, without causing dose-limiting toxicity or organ damage.
Technically, Rexin-G is a matrix-targeted nanoparticle that seeks out the biochemical hallmarks of pathology (pathotropic targeting), accumulates to high levels in tumors, and delivers a cytocidal (lethal) gene construct: a dominant-negative construct of the human Cyclin-G1 gene, a pivotal cell cycle control element. The capsule containing the therapeutic dnG1 gene is based on a murine retroviral core, which is devoid of viral genes and has been rendered certifiably replication incompetent—that is, it capable of delivering a therapeutic gene once, and only once. The integral tumor-targeting function is indeed profound, in that it is capable of penetrating primary and metastatic cancers, as well as cancers within the lymphatic system, with high efficiency, within a matter of hours, which represents the half-life of the active anti-cancer agent.
Development Milestones
- Rexin-G received Orphan Drug designation by the U.S. Food and Drug Administration
- Rexin-G received Accelerated Approval in the Philippines for use in all solid tumors
- Rexin-G is currently in clinical trials in the U.S. for advanced pancreatic, metastatic breast cancer, osteosarcoma, and soft tissue sarcoma (see Clinical Trials for more information).
How Rexin-G® Works
Each nanoparticle of Rexin-G is only 100 nanometers wide; yet despite its small size, it is a highly complex structure. Each component—the envelope, matrix, capsid, enzymes, and genetic material has its purpose, and in concert they enable Rexin-G to deliver a lethal payload of genetic medicine to cancer cells and their attendant blood supply. The payload is a tumor-killing designer gene, which selectively kills cancer cells and their associated blood supply, while sparing normal cells and healthy tissues.
The delivery of the lethal payload by the nanoparticles is “pathotropic,” meaning it is specifically targeted to diseased tissues. Rather than targeting the cancer cells themselves, Rexin-G efficiently targets a common histopathological property of all invasive tumors—much like ‘heat’ is the target of a heat-seeking missile. Pathotropic targeting allows Rexin-G to seek out and destroy tumors regardless of their location in the body, thereby reducing tumor burden, prolonging survival, and enhancing the patient’s quality-of-life.
How Rexin-G® is Delivered
Rexin-G is administered by simple intravenous infusion. As the nanoparticles are distributed by the general circulation, the exquisite targeting function serves to partition the genetic medicine into the tumors, thereby removing it from the blood stream. While the half-life of the active nanoparticle is rather limited (hours), the therapeutic gene that is efficiently delivered to the cancer cells and their ‘proliferative’ neovasculature acts over the next 24 hours or so to induce active cell death, which is seen as degeneration, anti-angiogenesis, and necrosis within the regressing tumors. Capable, by design, of delivering the therapeutic gene to dividing cells only, Rexin-G spares normal blood vessels, tissues, and organs, thus focusing the effects and improving safety. With the determination of overall-safety, Rexin-G has been re-formulated to higher-potency, where tumor control may be gained by simple infusions administered three times a week.
Major Highlights
- The first and so far only gene-delivery system to be validated in the clinic (Narture Reviews, Genetics, 2007)
- The only targeted, injectable genetic medicine that can be administered i.v.
- Designed to seek out and selectively destroy both primary and metastatic tumors
- Highly active as a single-agent in a broad spectrum of chemo-resistant cancers
About Metastatic Cancer
Cancer is a progressive illness, originating from primary tumors located in specific tissues or organs. Invasive tumor cells detach from the primary tumor and are carried to distant sites in the body through the bloodstream to neighboring tissues, creating a secondary or metastatic lesion. Metastatic tumors often present in essential organs, making treatment difficult. Standard treatment options for metastatic tumors include chemotherapy, radiation therapy, surgery or combinations of these treatment options, which often have limited success while causing severe side effects that often diminish the quality-of-life for the patient. Rexin-G is designed to seek out, combat, and abate metastatic cancers, regardless of its location in the body. While Rexin-G is, by itself, shown to be capable of halting the progression of otherwise intractable cancers in ongoing clinical trials—when standard treatments have failed—it is conceivable that Rexin-G may eventually be used strategically, in combination with other therapies.
Clinical Experience with Rexin-G
Early clinical and preclinical data suggest that Rexin-G is safe and effective when used as a single agent therapeutic for the treatment of chemo-resistant tumors. Upon critical analysis of clinical studies, Rexin-G has received Accelerated Approval for all solid tumors and is now available by prescription at several medical centers in the Philippines. In the United States, Rexin-G has completed Phase I testing and has received Orphan Drug Designation by the U.S. FDA for pancreas cancer, osteosarcoma, and soft tissue sarcomas. It is currently available as a second-line treatment for a limited number of patients in Advanced Phase I/II and Phase II confirmatory trials. (see Clinical Trials)
