Princeton, N.J.-based Soligenix Inc.’s quick response testing SGX-301 (synthetic hypericin) – with results shown after just six weeks of treatment – puts the company in strong position against cutaneous T-cell lymphoma (CTCL) as it readies for a “robust” discussion with the FDA.

The firm disclosed preliminary top-line results from its pivotal phase III FLASH (Fluorescent Light Activated Synthetic Hypericin) study, which enrolled 169 patients randomized 2-to-1 to receive drug or placebo and turned up statistically significant treatment response (p=0.04) in the Composite Assessment of Index Lesion Score primary endpoint assessment at eight weeks for the first cycle. A preliminary look at the open-label, cycle two results suggest a significantly more robust response rate after 12 weeks of SGX-301 treatment, and full data are expected to roll out in June. Shares (NASDAQ:SNGX) closed at $1.88, up 30 cents, or 19%.

CTCL, a rare type of non-Hodgkin’s lymphoma, is caused by malignant T cells that are attracted to the skin. In the first stages, the cells make their way to the surface in the form of patches, plaques and tumors. Later, the tumors may grow, with the T cells organizing and circulating. In early disease, survival rates reach around 88% over five years, and can resemble psoriasis. When the disease advances – which doctors find difficult to predict – the five-year survival rate dips to as low as 24%.

There’s no cure and no approved therapy for CTCL. “The problem is that the treatments themselves are not benign,” noted Soligenix’s chief medical officer, Richard Straube, with Zacks analyst David Bautz near the start of 2020. The harm done by cancer treatments to healthy cells “is particularly true in CTCL, where most of the current treatments are themselves mutagenic agents,” thus hiking the risk for secondary tumors such as melanoma. “Patients and their caregivers are faced with trying to treat a less lethal but difficult disease with treatments that raise their risk of a more lethal cancer,” along with skin damage.

Enter SGX-301, a topical drug ointment that the patient applies to lesions at home, the day before his or her doctor visit, in order to let malignant T cells absorb the hypericin. At the physician’s office, the subject is placed in front of a fluorescent light device and the lesions exposed to a specific wavelength of light for five to seven minutes. Tested in the phase III trial were two treatments per week for at least six weeks. It worked.

The prevalence of CTCL in the U.S. is estimated at between 20,000 and 40,000 patients. Each would be eligible for treatment with SGX-301 sometime in their long-term disease management. “Accounting for 20,000 patients in each of the U.S. and Europe, we conservatively estimate a total global market of$250 million,” Straube said.

Miragen top-line data in 3Q

Success with FLASH wasn’t unexpected. Analyst Bautz more recently checked in with Brian Poligone, director of the Rochester Skin Lymphoma Medical Group in Fairport, N.Y., an investigator in the FLASH study, who had recently presented a patient case study at the 4th World Congress of Cutaneous Lymphoma in Barcelona, Spain, describing a CTCL patient who achieved complete clearance of disease as a participant in the FLASH trial. The patient had previously failed at least five therapies. Poligone, in an interview with Bautz included in the latter’s Feb. 18 report, pointed to “many types of CTCL, and FMF (folliculotropic mycosis fungoides) is particularly difficult to treat, because it is deep within the skin layer. This often requires earlier adoption of systemic therapies, which are associated with more severe side effects. The success in this case is particularly meaningful because of the prior failures with standard therapies, including topical treatments, oral medications and phototherapy, before being treated with SGX-301.” He called the safety and long-term treatment effect “extremely impressive.” A potentially isolating rare disease, CTCL takes a while to get diagnosed, and most laypersons and physicians have never heard of it or have seen only one case.” Three main treatments exist for early stage CTCL: topical mustard, topical steroids and phototherapy. “All have their limitations,” he said.

Among the other players in CTCL is Boulder, Colo.-based Miragen Therapeutics Inc. with cobomarsen, an oligonucleotide inhibitor of miR-155, which has completed enrollment of 37 patients in the phase II trial called Solar. Top-line data are due in the third quarter of this year. CEO William Marshall, during a March 11 conference call on earnings, said officials will be “looking at the objective response rate with four months of durability in the skin. In the phase I studies, we had really looked at a variety of different parameters. We looked at different doses, different routes of administration, but what we had settled on was what we carried forward into Solar. At the 300-mg intravenous infusion dose, what we saw was in the neighborhood of a 50% objective response rate with four months of durability in the skin,” though the study was small. The comparator used in the study is vorinostat, a linear hydroxamic acid compound that inhibits HDAC activity and “an approved agent in the area,” he said. “If cobomarsen hits in the neighborhood of what we saw in phase I study and vorinostat performs [as it has in the past], we would then have a result that could provide statistical significance.”