OrbeShield® an oral immediate and delayed release formulation of the topically active corticosteroid beclomethasone dipropionate (BDP) is being developed for the treatment of GI ARS. BDP is a corticosteroid with predominantly topical activity that is approved for use in asthma, psoriasis and allergic rhinitis.

OrbeShield® has demonstrated positive pre-clinical results in a canine GI ARS model. The GI tract is highly sensitive to ionizing radiation and the destruction of epithelial tissue is one of the first effects of radiation exposure. The rapid loss of epithelial cells leads to inflammation and infection that are often the primary cause of death in acute radiation injury.

The application of OrbeShield® to acute GI ARS originated from other programs for oral BDP and is based on the properties of BDP to act locally in the GI tract to modulate local inflammation and epithelial cellular apoptosis. In most radiation scenarios, injury to the hematopoietic (blood) system and GI tract are the main determinants of survival.

Pre-clinical results indicate that dogs treated with OrbeShield® demonstrated statistically significant (p=0.04) improvement in survival with dosing at either 2 hours or 24 hours after exposure to lethal doses of total body irradiation (TBI) when compared to control dogs. OrbeShield® appears to significantly mitigate the damage to the GI epithelium caused by exposure to high doses of radiation using a well-established canine model of GI ARS.

To date, development of OrbeShield® has been largely supported by a $1 million NIH grant to Soligenix’s academic partner, the Fred Hutchinson Cancer Research Center.

OrbeShield® has been awarded Orphan Drug and Fast Track Designations by the FDA for the prevention of death following a potentially lethal dose of total body irradiation during or after a radiation disaster.

Radiation as a biological weapon

Radiation sickness, otherwise known as Acute Radiation Syndrome (ARS) occurs after individuals are exposed to high levels of ionizing radiation such as might be expected following detonation of a nuclear weapon, an improvised nuclear device, a “dirty bomb” or an accident near a nuclear power plant. Many survivors of the Hiroshima and Nagasaki atomic bombs in the 1940s and many of the firefighters who first responded after the Chernobyl Nuclear Power Plant accident in 1986 became ill with ARS. The panic caused by the recent Fukushima Daiichi nuclear disaster in Japan in 2011 has also highlighted the dangers of ARS. In the event of a nuclear disaster or terrorist detonation of a nuclear bomb, casualties exposed to >2 Gray (Gy) are at high risk for development of clinically significant ARS.

The three biological systems most affected by high levels of radiation are (1) the vascular system in the brain; (2) the mucosal cells lining the gastrointestinal tract, and (2) the hematopoietic (HP)/immune system. Damage to the brain’s vasculature, which occurs only at the very highest levels of radiation exposure, is irreversible and lethal. Gastrointestinal damage, including lesions within the gut followed by sepsis, is induced by high levels of radiation and is known as gastrointestinal acute radiation syndrome (GI ARS). Exposure to high doses of radiation exceeding 10-12 Gy causes GI ARS, which can result in death in 5-10 days. The extent of injury to the bone marrow and the GI tract are the principal determinants of survival after exposure to total body irradiation (TBI).