Following a fast track designation from the FDA earlier this year, a phase II clinical trial is being initiated to evaluate SGX942 as a treatment for oral mucositis in patients with head and neck cancer, announced Soligenix, Inc., the company developing the drug.
This phase II study will focus primarily on patients with tumors of the mouth and oropharynx who are experiencing oral mucositis as a consequence of treatment with intensity modulated radiation and chemotherapy. In June 2013, the FDA granted SGX942 a fast track designation, which is intended to speed up the development of treatments for unmet medical needs. Currently, there is not a specifically FDA approved therapeutic for oral mucositis in patients with head and neck cancer.
“We believe that the FDA's action in granting fast track designation is a validation of the potential of SGX942 to address this life-threatening, unmet medical need. We look forward to working closely with the FDA to expedite the SGX942 development program,” Christopher J. Schaber, PhD, the president and chief executive officer of Soligenix, said in a release in June.
The proof-of-concept phase II trial plans to enroll approximately 75 patients with head and neck cancer in order to evaluate the efficacy of SGX942. The trial plans to look specifically at a reduction in severity of oral mucositis and other key efficacy measures, such as patient reported outcomes, pharmacoeconomic parameters, and radiation-associated side effects, including trismus and xerostomia.
SGX942 is an innate defense regulator (IDR), which is a class of agents that comprises short synthetic peptides to simultaneously produce anti-inflammatory and anti-infective activity. This class of agent selectively boosts the protective mechanism of the immune system by mimicking natural antimicrobial defense peptides. Oral mucositis is thought to occur as a result of cell transcription factors released following DNA damage caused by chemoradiotherapy (CRT), which upregulate inflammatory cytokines. As a result, the anti-inflammatory mechanism of SGX942 is believed to prevent the pathophysiology of oral mucositis.
"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," Stephen T. Sonis, DMD, DMSc, clinical professor of oral medicine at Harvard School of Dental Medicine said in a statement. "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."
In preclinical studies, the treatment, which is also known by the broader research name SGX94, was examined in animal models and was found to relieve tissue damage caused by chemotherapy or radiation therapy. Additionally, the treatment was able to enhance the effectiveness of suboptimal dose antibiotics, without increasing inflammation.
In early clinical studies, SGX94 was evaluated in a dose-escalating placebo controlled phase I trial that enrolled 84 healthy patients. The main focus of the trial was to assess the side effect profile of the treatment. When administered by IV, over a 7-day period, SGX94 was found to have a strong safety profile. Additionally, the plasma clearance of the drug was found to be very rapid.
“Oral mucositis is a significant unmet medical need which ultimately impacts the tolerability of radiation and chemotherapy and therefore the survivability of cancer,” Sonis stated in a press release. “The lack of an effective treatment has frustrated healthcare providers and caused misery for innumerable patients. As an IDR, SGX942 directly targets a fundamental biological mechanism which leads to mucosal injury caused by radiation and chemotherapy.”
Severe oral mucositis occurs in >80% patients with head and neck cancer treated with radiation therapy. The debilitating side effect is also evident in approximately 40% of patients receiving treatment with high dose chemotherapy.