Yaupon Therapeutics, a privately held specialty pharmaceutical company, today announced positive top-line results from the pivotal multi-center study of its lead product candidate, a proprietary topical mechlorethamine gel for the treatment of early-stage cutaneous T-cell lymphoma (CTCL - stages I-IIa). The top-line data show that the study, which was conducted under a Special Protocol Assessment (SPA), achieved its primary and secondary endpoints. The top-line data are being presented for the first time today at the First World Congress of Cutaneous Lymphomas in Chicago, IL, by Stuart R. Lessin, MD, lead investigator of the study and director of dermatology at Fox Chase Cancer Center. Yaupon intends to file a New Drug Application (NDA) with the FDA later this year.
“We worked hard to create a topical mechlorethamine formulation that is stable, standardized and cosmetically elegant. We believe our product candidate has the potential to significantly improve the quality of life for patients.”
"This is an important achievement for patients living with CTCL. Mechlorethamine has been used for decades in a variety of non-controlled, pharmacy-based formulations that are not subject to consistent manufacturing practices. This is the first time we have a manufactured product that can be reviewed by the FDA and, hopefully, made widely available to patients," said Dr. Lessin. "My mentors published the original research in the early 1970s, so it is especially gratifying to me to have led this collaborative clinical study."
The pivotal trial was a randomized, observer-blinded clinical study designed to determine if Yaupon's proprietary topical mechlorethamine gel was non-inferior to a pharmacy-compounded formulation of mechlorethamine in Aquaphor® in patients with stage I-IIa CTCL. The study, conducted in 260 patients at 13 U.S. cancer centers, is the largest prospective study ever conducted in patients with CTCL.
To meet the criteria for non-inferiority, the lower limit of 95 percent confidence interval around the ratio of response rates had to be greater than 0.75. The primary endpoint for response was a 50 percent or greater improvement from baseline in the Composite Assessment of Index Lesion Severity (CAILS) scoring system. In the Intent to Treat population, 59 percent of the patients randomized to the Yaupon arm compared to 48 percent of the patients on the Aquaphor® arm achieved a response, resulting in a ratio of 1.226 and 95 percent confidence limit of 0.974 to 1.552, thus meeting the protocol defined endpoint. The most common adverse events were related to skin toxicity (local skin irritation, pruritis, contact dermatitis, erythema) and the withdrawal rates due to skin toxicity were similar in both arms.
"Achieving a positive outcome in this pivotal study is a major milestone for Yaupon and we believe that we are now well-positioned to file our first NDA later this year," said Robert Alonso, president and CEO of Yaupon. "We worked hard to create a topical mechlorethamine formulation that is stable, standardized and cosmetically elegant. We believe our product candidate has the potential to significantly improve the quality of life for patients."
Dating back to the 1950s, mechlorethamine has been used in a non-standardized way in both aqueous and paraffin (petroleum jelly) based formulations, either prepared by the patient or by special compounding pharmacies. The paraffin-based formulations are extremely greasy, which often leads to patient dissatisfaction. Yaupon's investigational mechlorethamine is a novel, quick-drying gel formulation made under Good Manufacturing Practices (GMPs). Yaupon expects to file an NDA later this year to seek FDA approval. The product candidate has been granted Fast Track Status and Orphan Drug Status by the FDA.
"Gaining formal FDA acceptance of a standardized topical mechlorethamine product has been one of the highest priorities for the Cutaneous Lymphoma Foundation since 1998," said Judy Jones, president and co-founder of the Cutaneous Lymphoma Foundation. "We are delighted with these study results and are hopeful that the product will soon be available for the 30,000 Americans living with CTCL."
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