Soligenix, Inc., a development stage biopharmaceutical company, has received the Investigational New Drug (IND) application clearance from US Food and Drug Administration (FDA) for OrbeShield (oral beclomethasone 17,21-dipropionate or oral BDP) for the mitigation of morbidity and mortality associated with the gastrointestinal acute radiation syndrome (GI-ARS). Soligenix has previously received Orphan Drug Designation for oral BDP for the prevention of death following a potentially lethal dose of total body irradiation during or after a radiation disaster.

Clearance of the IND allows Soligenix to initiate the development programme which will include safety and efficacy evaluations conducted in appropriate preclinical models as well as a phase 1/2 pharmacokinetic (PK)/pharmacodynamic (PD) study of OrbeShield in healthy adolescents and young adults.  The PK/PD data from the phase 1/2 study will provide the needed data to inform dose extrapolation from the animal studies to the appropriate dose in humans.

“We are very excited to advance the development of OrbeShield™ which we believe has the potential to be a safe and effective medical countermeasure in the event of a nuclear attack or radiation accident,” stated Kevin Horgan, MD, senior vice president & chief medical officer of Soligenix.  “We believe our proprietary two-tablet system has the pharmacological, clinical and manufacturing attributes necessary to potentially provide a substantial contribution to our national defense response systems so that we are optimally prepared in the event of a public health emergency such as nuclear accident or terrorist attack.”

ARS occurs after toxic radiation exposure and involves several organ systems, notably the bone marrow the GI tract and later the lungs.   In the event of a nuclear disaster or terrorist detonation of a nuclear bomb, casualties exposed to >2 Gy are at high risk for development of clinically significant ARS. Exposure to high doses of radiation exceeding 10-12 Gy causes acute GI injury which can result in death in 5-15 days.  The GI tract is highly sensitive due to the requirement for incessant proliferation of crypt stem cells and production of mucosal epithelium. The extent of injury to the bone marrow and the GI tract are the principal determinants of survival after exposure to TBI.  Although the hematopoietic syndrome can be rescued by bone marrow transplantation or growth factor administration, there is no established treatment or preventive measure for the GI damage that results from high-dose radiation exposure. Therefore, there is an urgent need to develop specific medical countermeasures against the lethal pathophysiological manifestations of radiation-induced GI injury.

OrbeShield contains BDP, a highly potent, topically active corticosteroid that has a local effect on inflamed tissue. OrbeShield is formulated for oral administration in GI-ARS patients as a single product consisting of two tablets; one tablet is intended to release BDP in the proximal portions of the GI tract and the other tablet is intended to release BDP in the distal portions of the GI tract.  BDP has been marketed in the United States and worldwide since the early 1970s as the active pharmaceutical ingredient in inhalation products for the treatment of patients with allergic rhinitis and asthma. Oral BDP may also have application in treating other GI disorders characterized by severe inflammation such as Crohn’s disease and radiation enteritis.

Soligenix is a development stage biopharmaceutical company developing products to treat serious inflammatory diseases where there remains an unmet medical need, as well as developing several biodefense vaccines and therapeutics.