Source: Sienna Biopharmaceuticals
Sienna Biopharmaceuticals, Inc. (NASDAQ:SNNA), a clinical-stage medical dermatology and aesthetics company, today announced results from a Phase 1b maximal use (MUse) pharmacokinetic (PK) and safety study of SNA-120 (pegcantratinib), a Phase 2b drug candidate being evaluated as a topical, nonsteroidal therapy to treat itch (pruritus) associated with psoriasis. SNA-120 is a topical tropomyosin receptor kinase A (TrkA) inhibitor that blocks nerve growth factor (NGF) signaling, which plays an important role in the pathogenesis of itch and psoriasis.
SNA-120 was developed using Sienna’s Topical by Design™ platform, which yields new chemical entities designed to deliver high local drug concentration in the target tissue and minimal to no systemic exposure for patients. SNA-120 directly targets the peripheral itch pathway in the psoriatic plaque.
The multicenter, open-label, Phase 1b study evaluated the PK and safety of 0.5 percent SNA-120 administered topically twice daily (BID) for four weeks. Circulating plasma levels of SNA-120 were measured in a total of 30 male and female subjects 18 years or older who had moderate to severe itch associated with moderate to severe psoriasis covering 20 percent or more body surface area.
The study, using an assay five times more sensitive than previously available, demonstrated minimal to no detectable systemic exposure after BID topical application of SNA-120 under maximal use conditions, with no accumulation of SNA-120 in the plasma. There were no associated clinically relevant changes in overall safety parameters (eg, laboratory assessments, vital signs and electrocardiograms [QTc duration]). A total of nine subjects reported 12 adverse events (AEs), only one of which was deemed related to the study drug and which was categorized as mild pruritus. Additionally, there were no dermal tolerability issues, no subject discontinuations due to an AE and no severe AEs or serious AEs (SAEs).
Improvements in pruritus and psoriasis were observed in exploratory efficacy analyses. For example, in a post hoc analysis, approximately 57 percent of subjects had at least a 4-grade improvement in the Itch Numeric Rating Scale (I-NRS). However, these efficacy data should be interpreted with caution, as this was a small, four-week study in patients with high body surface area involved (20 percent or greater) and no vehicle comparator.
“These results add to our overall understanding of the safety profile of SNA-120, and are consistent with results from our previous clinical studies with this molecule,” said Paul F. Lizzul, MD, PhD, Chief Medical Officer of Sienna Biopharmaceuticals. “At Sienna, we are putting our full weight behind solving itch and offering safe, innovative solutions for inflammatory skin diseases. We are taking a patient-centric approach to the treatment of psoriasis, recognizing there is more to psoriasis than meets the eye. We believe a non-steroidal topical approach directly targeting the peripheral itch pathway in the plaque and neurogenic inflammation could strike a better balance between efficacy and safety in treating this difficult condition.”
Chronic itch affects roughly 80 percent, or 6.3 million1, of the 7.9 million patients suffering from psoriasis in the United States2. It is an important – and often overlooked – symptom in patients with psoriasis. One study found that 50 percent of patients said they had difficulty sleeping due to itch, and 75 percent reported having to scratch until they bleed.3
“The itch that affects the majority of psoriasis patients can be as debilitating and harmful to their quality of life as the plaques themselves, yet there are no FDA-approved, targeted, topical medications available for chronic use that are addressing the bothersome itch that could extend beyond the plaque,” said Gil Yosipovitch, MD, FAAD, professor of dermatology at the Miller School of Medicine at the University of Miami and director of the Miami Itch Center. “Reducing the severity of itch is considered one of the most important treatment goals for patients, and physicians are increasingly focused on how to best address this debilitating symptom.”