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Soligenix (SNGX): What Can We Expect from the Ongoing Phase III Study of SGX942 based on the Phase II Results?

08/09/2017
By Grant Zeng, CFA

NASDAQ:SNGX

The Pivotal Phase III Trial of SGX942 for OM in Head and Neck Cancer Patients 

On July 27, 2017, Soligenix (NASDAQ:SNGX) announced that patient enrollment has been opened for its pivotal Phase III, multinational, randomized, double-blind, placebo-controlled study evaluating SGX942 (dusquetide) as a treatment for severe oral mucositis in patients with head and neck cancer receiving chemoradiation therapy (CRT).

This Phase III clinical trial is referred to as the “DOM–INNATE” study (Dusquetide treatment in Oral Mucositis – by modulating INNATE immunity).

The pivotal Phase III clinical trial (Study IDR-OM-02) will be:

• a highly powered, double-blind, randomized, placebo-controlled, multinational trial that will seek to enroll approximately 190 subjects with squamous cell carcinoma of the oral cavity and oropharynx who are 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 will be randomized to receive either 1.5 mg/kg SGX942 or placebo given twice a week during and for 2 weeks following completion of CRT. 

• The primary endpoint for the study will be the median duration of severe oral mucositis, which will be assessed by oral examination at each treatment visit and then through 6 weeks following completion of CRT. 

• Oral mucositis will be evaluated using the WHO Grading system. Severe oral mucositis is defined as a WHO Grade of ≥3. Subjects will be followed for an additional 12 months after the completion of treatment.

The study design incorporates feedback from the FDA as well as from the European Medicines Agency (EMA) via the Scientific Advice process. The Scientific Advice from the EMA indicates that a single, double-blind, placebo-controlled, multinational, Phase III pivotal study, if successful, in conjunction with results from the Phase II dose-ranging study, generally will be considered sufficient to support a marketing authorization application for potential licensure in Europe.

The Phase II Trial

The Phase III trial is also based on the positive and previously published Phase II results (Study IDR-OM-01) of SGX942 (NCT02013050) for the treatment of oral mucositis in head and neck cancer patients.

This Phase II trial was a randomized, double-blind, dose-ranging, placebo-controlled trial, which enrolled approximately 115 subjects across three SGX942 dose groups (1.5 mg/kg, 3.0 mg/kg and 6.0 mg/kg) and placebo, focused on demonstrating the safety and biologic activity of SGX942 in patients with tumors of the mouth and oropharynx who often experience debilitating oral mucositis as a consequence of tumor treatment with chemoradiation therapy (CRT).  

The primary efficacy assessment was the comparison of the incidence and/or duration of both ulcerative and severe oral mucositis throughout the subjects' 7-week course of CRT and for an additional 4 weeks thereafter.  Other key efficacy measures assessed patient reported outcomes, pharmacoeconomic parameters such as hospitalization and radiation-associated side effects including mouth stiffness and dryness.

The Initial Positive Phase II Data 

In December 2015, Soligenix announced initial positive results from the Phase II clinical trial.

In June 2016, the Company presented the data at the Multinational Association for Supportive Care in Cancer (MASCC) conference in Adelaide, Australia. 

The Phase II study enrolled 111 patients across three SGX942 dose groups (1.5, 3.0, and 6.0 mg/kg) and a placebo group and evaluated patients undergoing CRT for head and neck cancer.

This POC Phase II study achieved all objectives. In the 1.5 mg/kg treatment group, the median duration of severe oral mucositis was decreased by 50% in all patients, from 18 days to 9 days (p=0.099), meeting the prospectively defined statistical threshold of p<0.1. 

In a subgroup of patients receiving the most aggressive chemoradiation therapy, the median duration of severe oral mucositis was reduced even more from 30 days to 10 days (67%, p=0.04). The sample size was reasonable as well.

The 1.5 mg/kg dose was identified as the best dose for future trials.  

Further, a trend towards increased incidence of "complete response" of tumor at the one month follow up visit was observed (47% in placebo vs. 63% in SGX942 at 1.5 mg/kg).  Decreases in mortality and significant decreases in infection rate were also observed with SGX942 treatment and are being further evaluated. 

SGX942 was generally safe and well tolerated, consistent with the safety profile observed in the prior Phase I study conducted in 84 healthy volunteers. 

The Long-Term Follow Up Phase II Data 


The additional 12-month safety data remained consistent with the preliminary positive safety and efficacy findings from the Phase II study and provided further support for advancing SGX942 into a pivotal Phase IIb/III clinical trial.  

Long-term follow-up visits conducted throughout 2016 further demonstrated that SGX942 was safe, well-tolerated, and did not interfere with CRT as demonstrated by improved survival and tumor resolution at one and 12 months.  Overall, there were no drug-related toxicities identified in this study.

While the placebo population experienced the expected 12-month survival rate of approximately 80%, as defined in the Surveillance, Epidemiology, and End Results (SEER) statistics 1975-2012 from the National Cancer Institute, the SGX942 1.5 mg/kg treatment group reported a 12-month survival rate of 93% (7% mortality in the SGX942 1.5 mg/kg group compared to 19% in the placebo group).  Similarly, tumor resolution (complete response) at 12 months was better in the SGX942 1.5 mg/kg treatment group relative to the placebo population (80% in the 1.5 mg/kg group compared to 74% in the placebo group).

In addition to safety, evaluations of other secondary efficacy endpoints, such as the utilization of opioid pain medication, indicated that the SGX942 1.5 mg/kg treatment group had a 40% decrease in the use of opioids at the later stage of the treatment phase of the trial, when OM is usually most severe and expected to increase pain medication use.  This was in contrast to the placebo group, which demonstrated a 10% increase in use of opioids over this same period.  These results were consistent with the observed significant decrease in the duration of severe OM.  There were no differences observed in the rates of xerostomia (dry mouth) and trismus (limited jaw range of motion) across the SGX942 and placebo dose groups in the study.

What Can We Expect from the Ongoing Phase III Study of SGX942 based on the Phase II Results? 

We expect similar results from the Phase III trial will be achieved. Our expectation is based on the similar trial design between the Phase II and Phase III trial. The Phase III design introduces no unknown variables that haven't been looked at in the Phase II trial. 

The Phase III trial takes those key variables from the Phase II trial that had the strongest efficacy and safety signals. Here are some of the design highlights. 

• The patient inclusion/exclusion criteria are the same;
• Dose with the strongest anti-inflammatory impact 1.5 mg/kg (also lowest safest dose) from the Phase II was chosen for the Phase III trial;
• Primary endpoint that demonstrated strongest effect - demonstrating statistical significance, concomitant radiation and Cisplatin chemotherapy regimen of every 3rd week;
• Study highly powered; based on much more conservative assumptions (differences) than was demonstrated in the Phase II study between placebo and 1.5 mg/kg SGX942 dose group; 
• All key secondary endpoints at acute phase and 12-month follow-up being looked at in Phase III;
• Controlled roll-out of patient enrollment to assure clinical sites maintain strict adherence to protocol;
• One protocol that has the potential to support both US and European approval; incorporates both FDA and EMA feedback;
• No approved drugs in OM in head and neck cancer; allowing for FDA Fast-Track designation with potential for priority review upon NDA filing. 

All of the above similarities in the two trial design have the potential to contribute to increasing the probability of success in the pivotal Phase III trial. Given the statistical trend in survival seen at 12 months post-treatment, novel mechanism of action with p62 not only has demonstrated anti-inflammatory, anti-infective, and tissue healing properties, but may also play a potential role in the oncology setting. 

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