On June 24, 2020 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported it has completed patient enrollment in its Phase 3 DOM-INNATE ("Dusquetide treatment in Oral Mucositis – by modulating INNATE Immunity") study for SGX942 (dusquetide) in the treatment of oral mucositis (OM) in head and neck cancer (HNC) patients (Press release, Soligenix, JUN 24, 2020, View Source [SID1234561454]). The study successfully enrolled 268 subjects, following positive interim analysis, which included a prospectively defined, unblinded assessment of the study’s primary efficacy endpoint by an independent Data Monitoring Committee (DMC). With enrollment completed, top-line results are expected in the fourth quarter of 2020.
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SGX942 is a novel, first-in-class, Innate Defense Regulator (IDR) which both modulates inflammation and enhances anti-infective and tissue-healing pathways of the innate immune system. Study enrollment was temporarily extended as Soligenix assessed the potential impact of COVID-19 on the study (e.g., patient treatment compliance and completion of necessary assessments). With extra efforts by participating patients, physicians and clinical staff, the Company can now successfully report that the negative impact of the pandemic on the overall study was much less than initially anticipated. The study remains on-track to provide top-line results before the end of 2020.
"We are pleased to have completed enrollment and look forward to the top-line results in the fourth quarter, particularly in light of the DMC recommendation at the interim analysis which observed a beneficial drug effect," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "We continue to positively position this fast-tracked program for approval. With approximately $8 million in cash as of the end of the first quarter, not including our non-dilutive government funding, along with the at-the-market sales issuance agreement with B. Riley FBR, Inc. to judiciously supplement our cash runway as needed, we anticipate having sufficient capital to achieve multiple inflection points across our rare disease pipeline, including top-line results in the DOM-INNATE study. As there is no FDA approved drug for the treatment of oral mucositis in head and neck cancer or other solid tumor settings, we believe SGX942 has the potential to be the first approved therapy to address this unmet medical need and dramatically improve the lives of patients undergoing chemoradiation therapy (CRT)."
"SGX942 has the potential to have a significant impact on the lives of patients undergoing CRT for squamous cell carcinoma of the oral cavity and oropharynx," stated Richard Straube, MD, Senior Vice President and Chief Medical Officer of Soligenix. "We would like to thank the DMC members, our esteemed medical advisory board and our dedicated clinical investigators for their efforts in the design and conduct of this important clinical trial, as well as all the subjects that are participating in the trial. Our focus now is to complete the treatments for all subjects in both the US and Europe and to lock the study database, facilitating top-line results in the fourth quarter of 2020."
Based on the positive results demonstrated in the Phase 2 study of SGX942, the Phase 3 trial is a highly powered, double-blind, randomized, placebo-controlled, multicenter and multinational trial. The primary endpoint for the study is the median duration of severe oral mucositis, assessed by oral examination at each treatment visit and then through six weeks following completion of CRT. Oral mucositis is evaluated using the WHO (World Health Organization) Grading system. Other secondary measures, including incidence of severe oral mucositis, incidence and duration of ulcerative oral mucositis, and incidence of infection will also be assessed at topline or during the 12-month follow-up.
A prospectively defined interim analysis was conducted in August 2019 by an independent DMC and was used to verify the underlying assumptions defining the required sample size of the study to maintain its rigorous 90% statistical power. The DMC identified a beneficial SGX942 effect and accordingly adjusted the study sample size to approximately 260. The DMC did not identify any safety concerns. The interim recommendation is described in the August 2019 press release here.
About Oral Mucositis
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 HNC 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 HNC treated with CRT and is severe, causing inability to eat and/or drink, in >80% of patients. It 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.
In the pediatric population, head and neck cancer is a rarer occurrence and is caused by different underlying pathologies. The major types of HNC in children are lymphoma, sarcomas (including rhabdomyosarcomas), and neuroblastoma rather than squamous cell carcinoma, the major type of adult HNC cancers. Hematopoietic stem cell transplantation (HSCT), especially allogeneic transplantation with higher risk of oral mucositis, is more frequently used in the pediatric population than in adults when treating a number of primary tumor types, as seen in leukemia and lymphoma. Both treatment of HNC and HSCT are associated with high risk of oral mucositis in the pediatric population.
Oral mucositis remains an area of unmet medical need where there are currently no approved drug therapies in the context of any solid tissue tumors.
About the Phase 3 DOM-INNATE Study
This multinational, placebo-controlled, randomized study is targeted to enroll approximately 260 subjects with squamous cell carcinoma of the oral cavity and oropharynx, scheduled to receive a minimum total cumulative radiation dose of 55 Gy fractionated as 2.0-2.2 Gy per day with concomitant cisplatin chemotherapy given as a dose of 80-100 mg/m2 every third week. Subjects are randomized to receive either 1.5 mg/kg SGX942 or placebo given twice a week during and for two weeks following completion of CRT. The primary endpoint for the study is the median duration of severe oral mucositis, assessed by oral examination at each treatment visit and then through six weeks following completion of CRT. Oral mucositis is evaluated using the WHO (World Health Organization) Grading system. Severe oral mucositis is defined as a WHO Grade of ≥3. Subjects are to be followed for an additional 12 months after the completion of treatment. Soligenix has been working with leading oncology centers internationally, a number of which participated in the Phase 2 study.
About Dusquetide
Dusquetide (the active ingredient in SGX942) is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body’s reaction to both injury and infection towards an anti-inflammatory, anti-infective and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host’s innate immune system responses, increase survival after infections caused by 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, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis.
SGX942 has demonstrated safety in a Phase 1 clinical study in 84 healthy human volunteers. Positive efficacy results were demonstrated in an exploratory Phase 2 clinical study in 111 patients with oral mucositis due to CRT for HNC. Soligenix is working with leading oncology centers in the US and Europe to advance SGX942 in oral mucositis with the conduct of a pivotal Phase 3 clinical trial referred to as the "DOM–INNATE" study (Dusquetide treatment in Oral Mucositis – by modulating INNATE immunity).
SGX942 has received Fast Track Designation from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in HNC patients, as well as Promising Innovative Medicine designation in the United Kingdom by the Medicines and Healthcare Products Regulatory Agency for the treatment of severe oral mucositis in HNC patients receiving CRT. In addition, products containing the same active ingredient, dusquetide, have been granted Fast Track Designation as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis and Orphan Drug Designations in the treatment of MAS and the treatment of acute radiation syndrome.
Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada. Soligenix has received partial funding from NIH for its oral mucositis clinical studies. The Phase 2 study was supported with a Phase I SBIR grant (#R43DE024032) award, with the Phase 3 study being supported by a Phase II SBIR grant (#R44DE024032) award.
In addition, a high level review of the IDR technology platform is available here.