PRISM Q&A CORNER
Ellen Kim , MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, and Professor of Dermatology at the Hospital of the University of PennsylvaniaSoligenix’s HyBryte™: Lighting the Way Towards Commercial Success with Promising FLASH Study Results
Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin’s lymphoma with no FDA-approved first-line treatments on the market. Approximately 3,000 new CTCL cases are diagnosed in the United States each year and more than 20,000 patients are living with CTCL. Late-Stage biotech company Soligenix (Nasdaq: SNGX) is developing and moving toward potential commercialization of HyBryte™ (synthetic hypericin) as a novel first-in-class photodynamic therapy that uses safe visible light for the treatment of early-stage CTCL.
Ellen Kim, MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, and Professor of Dermatology at the Hospital of the University of Pennsylvania was the Lead Principal Investigator for Soligenix’s Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study in CTCL.
On July 9th, Dr. Kim publicly disclosed interim results from an ongoing open-label, investigator-initiated study (IIS) she sponsored evaluating extended HyBryte™ treatment for up to 12 months in patients with early-stage CTCL. This study is currently being supported by a $2.6 million Orphan Products Development Grant awarded by the U.S. Food and Drug Administration (FDA).
We had the chance to sit down with her to discuss the positive preliminary findings as well as what’s next for this potentially breakthrough treatment.
A:Certainly, thus far in our IIS we have enrolled and treated six patients with HyBryte™ spanning a time frame up to 44 weeks. While the sample size is small, the results have been dramatic with 3-out-of-4 – that’s 75% of the patients – responding positively to HyBryte™ therapy through at least 12 weeks of treatment. These individuals have already achieved “Treatment Success,” as predefined in the study’s protocol of ≥50% improvement in their cumulative mCAILS (modified Composite Assessment of Index Lesion Severity) score compared to the baseline. Of the three Treatment Successes, two were achieved within the first 12 weeks of treatment and the third within 18 weeks.
Regarding the other three enrolled patients, at this interim data cut, two just started receiving HyBryte™ and had not yet reached the first evaluation milestone visit. The other individual has seen significant improvement through 18 weeks of treatment, but the results have not yet reached the success threshold. I should say that this is an open-label trial, so no placebo is being administered. All the patients know they are receiving HyBryte™, which appears to be safe and well tolerated in all patients, consistent with prior HyBryte™ studies. There have not been any treatment related adverse events reported so far, which is also very important when treating a chronic cancer like CTCL.
As you would imagine, these initial results are very exciting and build upon the increasing body of positive HyBryte™ data as we move into the 18-week confirmatory placebo-controlled study later this year.
Q:A:We were interested in studying HyBryte™ efficacy and safety in early stage CTCL patients given as a continuous treatment over a 1-year period, in contrast to the Phase 3 FLASH study, which consisted of three 6-week treatment cycles with 2-week rest periods between cycles. The first 6-week cycle was double blind and placebo-controlled, and was followed by two open label 6 week cycles in which all patients received HyBryte™.
Registration trials for drug approvals, like FLASH, must follow strict FDA guidelines during Phases 1-3 evaluation stages to determine the drugs performance in a controlled setting against the predetermined primary and secondary endpoints of the study protocol. If those endpoints are achieved with both clinical and statistical significance as outlined in the various designs of the trials, then the FDA can decide if the safety and efficacy benefits of the medicine outweigh any health risks or adverse events that might have come up during a study. While registration studies are required for FDA approval, an IIS, like ours, gives a glimpse as to how drugs can be used in a “real world” setting. This study is an open-label design with no placebo or control arm so all patients receive the study medicine. Subjects apply the ointment to their lesions themselves as they typically would prior to receiving their visible light treatment in the clinic. As the study progresses, patients have the option to self-administer the light treatments using a home unit to provide real-world evidence to the data set we’re gathering. IIS research has the potential to provide important data to support and extend positive Phase 2 and 3 clinical trial results for much needed medicines, as is the case with HyBryte™.
As doctors, we deal with all sorts of patients and situations every day that might not fit neatly into a typical clinical trial. That’s where studies, like an IIS, become important. They help answer those tricky questions that can arise in everyday medical practice.
It’s worth pointing out that this IIS is funded by an Orphan Products Development Grant from the FDA to support the evaluation of HyBryte™ for expanded treatment in patients with early-stage CTCL, including in the home use setting. My university was awarded the $2.6 million grant, which can be used over 4 years.
Q:A:We’re actively recruiting study participants. The details of the trial such as inclusion and exclusion criteria, study design, outcome measures and more are readily available online at ClinicalTrials.gov. The study is listed under the trial name “Assessment of Treatment with Visible Light Activated Synthetic Hypericin Ointment in Mycosis Fungoides Patients” (RW-HPN-MF-01). As we’ve discussed, this is an open-label clinical trial enrolling up to 50 patients at select U.S. clinical centers. Enrolled patients are treated for up to 12 months with HyBryte™, ointment, which is applied to the cancerous lesions on the skin about 24 hours prior to twice a week dosing with visible light activation in the clinic.
It’s important to note that this study also allows for potential transition to a “real-world” setting with home-use of HyBryte™. The primary endpoint for the study is evaluating the number of treatment successes defined as ≥50% reduction in the cumulative mCAILS score from baseline to end of the treatment.
Q:A:To answer your first question, confirmatory studies in chronic orphan diseases are sometimes requested by heath authorities even when your first Phase 3 clinical trial may have been successful, as is the case with the HyBryte™ Phase 3 FLASH study in CTCL.
The second confirmatory Phase 3 study, which will be called FLASH2, is expected to be initiated before the end of this year. It will be a randomized, double-blind, placebo-controlled, multicenter study that will enroll approximately 80 patients with early-stage CTCL. While FLASH2 replicates the same double-blind, placebo-controlled design used in the first successful Phase 3 FLASH study that consisted of three 6-week treatment cycles (18 weeks total); this second study extends the assessment to 18 weeks of continuous treatment without any “between-cycle” treatment breaks, as was done in the FLASH study. The primary endpoint assessment in FLASH2 will occur at the end of the 18-week timepoint, whereas the primary endpoint assessment in the first FLASH study occurred at the end of the first 6-week treatment cycle. The extended treatment for a continuous 18 weeks in a single double blind, placebo-controlled cycle is expected to statistically demonstrate HyBryte’s™ increased effect over a more prolonged, “real world” treatment course. FLASH2 will keep all important clinical study design components the same as in the first FLASH study, including the primary endpoint and key inclusion-exclusion criteria, but an even more robust response in the FLASH2 study is anticipated, and the early data from our IIS seems to confirm that hypothesis to this point.
Q:A:In the short term, we expect to issue results from the IIS as data warrants, in compliance with Good Clinical Trial Practices. Additionally, we are optimistic that we’ll be able to announce the launch of FLASH2 by the end of the year. Given the extensive engagement with the CTCL community, including many of the CTCL key opinion leaders, as well as our previous trial experience with this disease in FLASH, we anticipate an accelerated patient enrollment for this study.
There’s even the possibility that we may be able to enroll previously identified and treated HyBryte™ patients from the original FLASH study, which would also help with accelerating enrollment in FLASH2.
Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin’s lymphoma with no FDA-approved first-line treatments on the market. Approximately 3,000 new CTCL cases are diagnosed in the United States each year and more than 20,000 patients are living with CTCL. Late-Stage biotech company Soligenix (Nasdaq: SNGX) is developing and moving toward potential commercialization of HyBryte™ (synthetic hypericin) as a novel first-in-class photodynamic therapy that uses safe visible light for the treatment of early-stage CTCL.
Ellen Kim, MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, and Professor of Dermatology at the Hospital of the University of Pennsylvania was the Lead Principal Investigator for Soligenix’s Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study in CTCL.
On July 9th, Dr. Kim publicly disclosed interim results from an ongoing open-label, investigator-initiated study (IIS) she sponsored evaluating extended HyBryte™ treatment for up to 12 months in patients with early-stage CTCL. This study is currently being supported by a $2.6 million Orphan Products Development Grant awarded by the U.S. Food and Drug Administration (FDA).
We had the chance to sit down with her to discuss the positive preliminary findings as well as what’s next for this potentially breakthrough treatment.
Certainly, thus far in our IIS we have enrolled and treated six patients with HyBryte™ spanning a time frame up to 44 weeks. While the sample size is small, the results have been dramatic with 3-out-of-4 – that’s 75% of the patients – responding positively to HyBryte™ therapy through at least 12 weeks of treatment. These individuals have already achieved “Treatment Success,” as predefined in the study’s protocol of ≥50% improvement in their cumulative mCAILS (modified Composite Assessment of Index Lesion Severity) score compared to the baseline. Of the three Treatment Successes, two were achieved within the first 12 weeks of treatment and the third within 18 weeks.
Regarding the other three enrolled patients, at this interim data cut, two just started receiving HyBryte™ and had not yet reached the first evaluation milestone visit. The other individual has seen significant improvement through 18 weeks of treatment, but the results have not yet reached the success threshold. I should say that this is an open-label trial, so no placebo is being administered. All the patients know they are receiving HyBryte™, which appears to be safe and well tolerated in all patients, consistent with prior HyBryte™ studies. There have not been any treatment related adverse events reported so far, which is also very important when treating a chronic cancer like CTCL.
As you would imagine, these initial results are very exciting and build upon the increasing body of positive HyBryte™ data as we move into the 18-week confirmatory placebo-controlled study later this year.
We were interested in studying HyBryte™ efficacy and safety in early stage CTCL patients given as a continuous treatment over a 1-year period, in contrast to the Phase 3 FLASH study, which consisted of three 6-week treatment cycles with 2-week rest periods between cycles. The first 6-week cycle was double blind and placebo-controlled, and was followed by two open label 6 week cycles in which all patients received HyBryte™.
Registration trials for drug approvals, like FLASH, must follow strict FDA guidelines during Phases 1-3 evaluation stages to determine the drugs performance in a controlled setting against the predetermined primary and secondary endpoints of the study protocol. If those endpoints are achieved with both clinical and statistical significance as outlined in the various designs of the trials, then the FDA can decide if the safety and efficacy benefits of the medicine outweigh any health risks or adverse events that might have come up during a study. While registration studies are required for FDA approval, an IIS, like ours, gives a glimpse as to how drugs can be used in a “real world” setting. This study is an open-label design with no placebo or control arm so all patients receive the study medicine. Subjects apply the ointment to their lesions themselves as they typically would prior to receiving their visible light treatment in the clinic. As the study progresses, patients have the option to self-administer the light treatments using a home unit to provide real-world evidence to the data set we’re gathering. IIS research has the potential to provide important data to support and extend positive Phase 2 and 3 clinical trial results for much needed medicines, as is the case with HyBryte™.
As doctors, we deal with all sorts of patients and situations every day that might not fit neatly into a typical clinical trial. That’s where studies, like an IIS, become important. They help answer those tricky questions that can arise in everyday medical practice.
It’s worth pointing out that this IIS is funded by an Orphan Products Development Grant from the FDA to support the evaluation of HyBryte™ for expanded treatment in patients with early-stage CTCL, including in the home use setting. My university was awarded the $2.6 million grant, which can be used over 4 years.
We’re actively recruiting study participants. The details of the trial such as inclusion and exclusion criteria, study design, outcome measures and more are readily available online at ClinicalTrials.gov. The study is listed under the trial name “Assessment of Treatment with Visible Light Activated Synthetic Hypericin Ointment in Mycosis Fungoides Patients” (RW-HPN-MF-01). As we’ve discussed, this is an open-label clinical trial enrolling up to 50 patients at select U.S. clinical centers. Enrolled patients are treated for up to 12 months with HyBryte™, ointment, which is applied to the cancerous lesions on the skin about 24 hours prior to twice a week dosing with visible light activation in the clinic.
It’s important to note that this study also allows for potential transition to a “real-world” setting with home-use of HyBryte™. The primary endpoint for the study is evaluating the number of treatment successes defined as ≥50% reduction in the cumulative mCAILS score from baseline to end of the treatment.
To answer your first question, confirmatory studies in chronic orphan diseases are sometimes requested by heath authorities even when your first Phase 3 clinical trial may have been successful, as is the case with the HyBryte™ Phase 3 FLASH study in CTCL.
The second confirmatory Phase 3 study, which will be called FLASH2, is expected to be initiated before the end of this year. It will be a randomized, double-blind, placebo-controlled, multicenter study that will enroll approximately 80 patients with early-stage CTCL. While FLASH2 replicates the same double-blind, placebo-controlled design used in the first successful Phase 3 FLASH study that consisted of three 6-week treatment cycles (18 weeks total); this second study extends the assessment to 18 weeks of continuous treatment without any “between-cycle” treatment breaks, as was done in the FLASH study. The primary endpoint assessment in FLASH2 will occur at the end of the 18-week timepoint, whereas the primary endpoint assessment in the first FLASH study occurred at the end of the first 6-week treatment cycle. The extended treatment for a continuous 18 weeks in a single double blind, placebo-controlled cycle is expected to statistically demonstrate HyBryte’s™ increased effect over a more prolonged, “real world” treatment course. FLASH2 will keep all important clinical study design components the same as in the first FLASH study, including the primary endpoint and key inclusion-exclusion criteria, but an even more robust response in the FLASH2 study is anticipated, and the early data from our IIS seems to confirm that hypothesis to this point.
In the short term, we expect to issue results from the IIS as data warrants, in compliance with Good Clinical Trial Practices. Additionally, we are optimistic that we’ll be able to announce the launch of FLASH2 by the end of the year. Given the extensive engagement with the CTCL community, including many of the CTCL key opinion leaders, as well as our previous trial experience with this disease in FLASH, we anticipate an accelerated patient enrollment for this study.
There’s even the possibility that we may be able to enroll previously identified and treated HyBryte™ patients from the original FLASH study, which would also help with accelerating enrollment in FLASH2.
