Cyprium Therapeutics, Inc. (“Cyprium”), a Fortress Biotech, Inc. (Nasdaq: FBIO) (“Fortress”) partner company, with support from its licensing partner Sentynl Therapeutics, Inc. (“Sentynl”), a wholly owned subsidiary of Cadila Healthcare Limited (“Zydus”), today announced positive results from an efficacy and safety analysis of data integrated from two completed pivotal studies in patients with Menkes disease treated with CUTX-101, copper histidinate (CuHis). In both pre-specified primary and secondary efficacy analyses, treatment with CUTX-101 demonstrated a significantly greater median overall survival (OS) compared to untreated historical control patients. These data will be presented as a virtual poster at the 2021 American Academy of Pediatrics National Conference & Exhibition. More information on the poster is listed below:
Virtual Poster Title: Copper Histidinate Treatment for Menkes Disease (Kinky Hair Syndrome)
Presentation Date: Friday, October 08, 2021
Session: (VH1410) Section on Advances in Therapeutics and Technology Program
Authors: Stephen G. Kaler, M.D., M.P.H., Shama Munim, M.S., Michael Chen, Ph.D., Robert Niecestro, Ph.D., Lung S. Yam, M.D., Ph.D.
“There is a significant unmet need for an approved treatment for patients with Menkes disease. These positive data demonstrate the potential of CUTX-101 to be an effective therapy for patients with this devastating disease. We look forward to working with the U.S. Food and Drug Administration (“FDA”) to begin our rolling submission of a new drug application (“NDA”) for CUTX-101 in the fourth quarter of this year,” said Lung S. Yam, M.D., Ph.D., President and Chief Executive Officer of Cyprium.
In two completed open-label, single-arm, single-site studies, 129 patients with Menkes disease were treated with CUTX-101 (1450 mcg CUTX-101, equivalent to 250 mcg elemental copper) administered subcutaneously twice daily until 12 months of age, and once daily thereafter, for a total duration of up to three years. Sixty-six patients born after 1999 and with severe loss-of-function ATP7A mutations from these two studies were combined and categorized into an Early Treatment cohort (CuHis-ET; treatment initiated within 4 weeks of birth, corrected for prematurity, n=31) and a Late Treatment cohort (CuHis-LT; treatment initiated after 4 weeks of birth, n=35). A historical control cohort of 18 Menkes disease patients who had not been treated with CUTX-101 were enrolled (including 18 in historical control-early treatment cohort (HC-ET); 17 of whom were also included in historical control-late treatment (HC-LT)). Efficacy of CUTX-101 was assessed by comparing CuHis-ET to untreated HC-ET, and CuHis-LT to untreated HC-LT, using OS as the primary and secondary efficacy endpoints, respectively.
The primary efficacy endpoint comparing CuHis-ET to HC-ET and the secondary efficacy endpoint comparing CuHis-LT to HC-LT were both met. Overall, a 79% reduction in risk of death was observed in CuHis-ET patients compared with HC-ET patients and median OS was 177.1 and 16.1 months, respectively with a hazard ratio (HR) of (95% CI) = 0.208 (0.094, 0.463) p<0.0001. A 75% reduction in the risk of death was also observed in CuHis-LT patients compared with HC-LT subjects and median OS was 62.4 and 17.6 months, respectively; HR (95% CI) = 0.253 (0.119, 0.537); p<0.0001.
Clinical benefit was greater for patients who were treated within four weeks of birth with CUTX-101, emphasizing the importance of early identification, including newborn screening and prompt initiation of treatment. A newborn screening test for Menkes disease is currently in development.
CUTX-101 was shown to be well tolerated. In CuHis-ET and CuHis-LT cohorts, the most common treatment emergent adverse events were pneumonia (30.3%), seizures (21.2%), dehydration (18.2%), failure to thrive (16.7%), and respiratory distress (15.2%) and no patient discontinued due to an adverse event considered related to treatment.
Stephen G. Kaler, M.D., M.P.H., a physician-scientist in the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children’s Hospital, is Principal Investigator of the clinical studies and is also a professor of Pediatrics and Genetics at The Ohio State University College of Medicine.
“We are grateful to the patients and their families who have participated in the clinical studies over the years. We would also like to thank Dr. Kaler for his ongoing efforts and dedication to improving therapies for this devastating pediatric disease. We commend the Cyprium team who has worked diligently to advance the CUTX-101 program and will remain steadfast and focused on bringing this therapy to patients,” said Dr. Yam.
Cyprium has partnered with Sentynl Therapeutics, Inc., a U.S.-based specialty pharmaceutical company owned by the Zydus Group, to bring CUTX-101 to market. Cyprium will retain development responsibility of CUTX-101 through approval of the NDA by the FDA, and Sentynl will be responsible for commercialization of CUTX-101 as well as progressing newborn screening activities.
“We are encouraged by the clinical data presented at the 2021 American Academy of Pediatrics National Conference & Exhibition and are excited to continue to support Cyprium’s efforts to advance CUTX-101 through NDA approval as we parallel significant efforts in Disease Awareness education and Newborn Screening. These developments support the group’s ongoing endeavor to address unmet healthcare needs,” said Matthew Heck, President and Chief Executive Officer of Sentynl.
About Menkes Disease
Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of copper transporter ATP7A. The minimum birth prevalence for Menkes disease is believed to be 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment (Kaler SG, Ferreira CR, Yam LS. Estimated birth prevalence of Menkes disease and ATP7A-related disorders based on the Genome Aggregation Database (gnomAD). Molecular Genetics and Metabolism Reports 2020 June 5;24:100602). The condition is characterized by distinctive clinical features, including sparse and depigmented hair (“kinky hair”), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, failure to thrive, and neurodevelopmental delays. Mortality is high in untreated Menkes disease, with many patients dying before the age of three years old. Milder versions of ATP7A mutations are associated with other conditions, including Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy. Currently, there is no FDA-approved treatment for Menkes disease and its variants.