Soligenix, Inc., a clinical stage biopharmaceutical company, has initiated a phase 2, randomized, double-blind, placebo-controlled study evaluating SGX942, a first-in-class innate defense regulator (IDR), as a treatment for oral mucositis in patients undergoing chemoradiation (CRT) therapy for head and neck cancer.   

This phase 2 study is a multicenter trial focused on patients with tumors of the mouth and oropharynx who often experience debilitating oral mucositis as a consequence of tumor treatment with intensity modulated radiation and chemotherapy.  The primary efficacy will be assessed on the basis of the incidence and duration of both ulcerative and severe oral mucositis throughout the course of radiation treatment.  Other key efficacy measures will assess patient reported outcomes, pharmacoeconomic parameters such as hospitalization and radiation-associated side effects including mouth stiffness (trismus) and dryness (xerostomia).

"Oral mucositis remains a debilitating side effect of cancer treatments and is particularly severe and prevalent in head and neck cancer patients.  Our current understanding of oral mucositis highlights the role of the innate immune response in exacerbating the damage done by CRT," stated Stephen T. Sonis, DMD, DMSc, Clinical Professor of Oral Medicine at Harvard School of Dental Medicine and Member of the Soligenix Oral Mucositis Medical Advisory Board.  "SGX942 is the first innate defense regulator in development for oral mucositis and its mechanism offers a promising option to treat the debilitating consequences of CRT."

"The initiation of the oral mucositis phase 2 trial marks another important next step in the development of SGX942 and is our first opportunity to demonstrate the potential clinical efficacy of SGX942," stated Christopher J Schaber, president and chief executive officer of Soligenix. "We look forward to working with our esteemed Medical Advisory Board and clinical investigators to complete this study."

Mucositis is the clinical term for damage done to the mucosa by anticancer therapies. It can occur in any mucosal region, but is most commonly associated with the mouth, followed by the small intestine.  It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of mucositis, that mucositis affects approximately 500,000 people in the US per year and occurs in 40% of patients receiving chemotherapy. Mucositis can be severely debilitating and can lead to infection, sepsis, the need for parenteral nutrition and narcotic analgesia. The gastrointestinal damage causes severe diarrhea. These symptoms can limit the doses and duration of cancer treatment, leading to sub-optimal treatment outcomes.

The mechanisms of mucositis have been extensively studied and have been recently linked to the interaction of chemotherapy and/or radiation therapy with the innate defense system.  Bacterial infection of the ulcerative lesions is now regarded as a secondary consequence of dysregulated local inflammation triggered by therapy-induced cell death, rather than as the primary cause of the lesions.

It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of oral mucositis, that oral mucositis in head and neck cancer is a subpopulation of approximately 90,000 patients in the US, with a comparable number in Europe.  Oral mucositis almost always occurs in patients with head and neck cancer treated with radiation therapy (>80% incidence of severe mucositis) and is common (40-100% incidence) in patients undergoing high dose chemotherapy and hematopoietic cell transplantation, where the incidence and severity of oral mucositis depends greatly on the nature of the conditioning regimen used for myeloablation.

Oral mucositis in head and neck cancer remains an area of unmet medical need where there are currently no approved drug therapies.  

SGX942 is an innate defense regulator (IDR), a new class of short, synthetic peptides that has a novel mechanism of action in that it has simultaneous anti-inflammatory and anti-infective activity.  IDRs have no direct antibiotic activity but modulate host responses, increasing survival after infections with a broad range of bacterial Gram-negative and Gram-positive pathogens, as well as accelerating resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy.  SGX942 has demonstrated safety in a phase 1 clinical study in healthy human volunteers and efficacy in numerous animal disease models including mucositis, colitis, skin infection and other bacterial infections.  SGX942 and related analogs has a strong intellectual property position, including composition of matter.  SGX942 was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada and approximately $40 million has been put towards its development to date, inclusive of government grants.  

SGX942 has received fast track designation 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.  Fast track is a designation that the FDA reserves for a drug intended to treat a serious or life-threatening condition and one that demonstrates the potential to address an unmet medical need for the condition.  Fast track designation is designed to facilitate the development and expedite the review of new drugs.  For instance, should events warrant, Soligenix will be eligible to submit a new drug application (NDA) for SGX942 on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete submission.  Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately six months.  

Soligenix is a clinical 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.