Soligenix, Inc, a late-stage biopharmaceutical company, announced that the Office of Orphan Products Development of the US Food and Drug Administration (FDA) has granted orphan drug designation to the active ingredient dusquetide for treatment of macrophage activation syndrome (MAS).

Dusquetide has previously received orphan drug designation for the treatment of acute radiation syndrome (ARS). Dusquetide is an innate defense regulator (IDR), a new class of short, synthetic peptides that accelerates bacterial clearance and resolution of tissue damage while modulating inflammation following exposure to a variety of agents including bacterial pathogens, trauma, radiation and/or chemotherapy.

The US Orphan Drug Act is intended to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders. In addition to providing a seven-year term of market exclusivity upon final FDA approval, orphan drug designation also positions Soligenix to be able to leverage a wide range of financial and regulatory benefits, including government grants for conducting clinical trials, waiver of expensive FDA user fees for the potential submission of a New Drug Application, and certain tax credits.

"The FDA's decision to grant dusquetide orphan drug designation signifies an important step for Soligenix as we continue to expand our biotherapeutics pipeline and the many potential applications of our novel IDR technology," stated Christopher J. Schaber, PhD, president and chief executive officer of Soligenix.

"Dusquetide's activity in preclinical models has demonstrated the potential to enhance mechanisms of the innate immune system to clear infection and modulate the inflammatory response, the critical attributes of this syndrome. The marketing exclusivity that orphan drug designation imparts adds significantly to the existing intellectual property surrounding dusquetide."

Macrophage activation syndrome (MAS) is characterized by a highly stimulated but ineffective immune response; however, its pathogenesis is poorly understood. MAS has many similarities with that of the other forms of hemophagocytic lymphohistiocytosis. MAS is a life-threatening complication of rheumatic disease that, for unknown reasons, occurs much more frequently in individuals with systemic juvenile idiopathic arthritis (SJIA). Besides SJIA, systemic lupus erythematosus (SLE), and Kawasaki disease are two other rheumatologic conditions in which MAS appears to occur somewhat more frequently than in other diseases. In adults, based on limited epidemiologic studies, MAS is seen most frequently in association with adult onset Still's disease, SLE, and various vasculitic syndromes. MAS is characterized by pancytopenia, liver insufficiency, coagulopathy and neurologic symptoms and is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. Despite treatment, fatalities still occur with a mortality rate in the range of 10-20%.

Dusquetide is an innate defense regulator (IDR), a new class of short, synthetic peptide. It has a novel mechanism of action in that it modulates the body's reaction to both injury and infection towards an anti-inflammatory and an anti-infective response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections with a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, melioidosis, MAS and other bacterial infections. In a published mouse model of MAS, dusquetide was shown to reduce the pancytopenia, reduced IL-12 responses and improve body weight maintenance.

SGX942 (the drug product containing dusquetide) has demonstrated safety in a phase 1 clinical study in 84 healthy human volunteers. Recently, SGX942 has demonstrated preliminary efficacy and safety in an exploratory phase 2 clinical study in 111 patients with oral mucositis due to chemoradiation (CRT) therapy for head and neck cancer. Consistent with preclinical findings, SGX942 at a dose of 1.5 mg/kg demonstrated positive improvements in decreasing the duration of severe oral mucositis by 50% overall compared to the placebo group, from 18 days to 9 days (p=0.099). In patients at highest risk of oral mucositis (e.g., those exposed to the most aggressive concomitant chemotherapy), the reduction in the duration of severe oral mucositis was even more significant at 67% when treated with SGX942 1.5 mg/kg, from 30 days to 10 days (p=0.04). The p-values meet the prospectively defined statistical threshold of p<0.1 in the study protocol. Additional observations included an improved tumor response to CRT therapy at the one month follow up visit, as well as decreases in infection rate.

Dusquetide and related analogs have a strong intellectual property position, including composition of matter. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada.

Drug products containing dusquetide have also received Fast Track Designations from the US Food and Drug Administration (FDA) for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in head and neck cancer patients, and as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis.