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Cyprium Reports Positive Data for CUTX-101 in Pivotal Studies in Menkes Disease

October 14, 2021

Cyprium Therapeutics reported 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.

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.

“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”, said Lung Yam, president and CEO of Cyprium.

Cyprium plans to begin a rolling submission of New Drug Application to the U.S. Food and Drug Administration for CUTX-101 in the fourth quarter of 2021, with the potential that it could be first FDA-approved treatment for 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. The condition is characterized by distinctive clinical features, including sparse and depigmented 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.

Cyprium’s CUTX-101 is a subcutaneous injectable formulation of copper histidinate. 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 and a Late Treatment cohort.

A historical control cohort of 18 Menkes disease patients who had not been treated with CUTX-101 were enrolled in historical control-early treatment cohort; 17 of whom were also included in historical control-late treatment. 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 percent 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. A 75 percent 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.

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 percent), seizures (21.2 percent), dehydration (18.2 percent), failure to thrive (16.7 percent), and respiratory distress (15.2 percent) and no patient discontinued due to an adverse event considered related to treatment.

Cyprium has partnered with Sentynl Therapeutics, 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 U.S. Food and Drug Administration, and Sentynl will be responsible for commercialization of CUTX-101 as well as progressing newborn screening activities. 

In March 2017, Cyprium entered into a Cooperative Research and Development Agreement with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the NIH, to advance the clinical development of CUTX-101 for the treatment of Menkes disease. In addition, Cyprium and NICHD entered a worldwide, exclusive license agreement to develop and commercialize AAV-based gene therapy, called AAV-ATP7A, to deliver working copies of the copper transporter that is defective in patients with Menkes disease, and to be used in combination with CUTX-101.

CUTX-101 was granted FDA Breakthrough Therapy, Fast Track and Rare Pediatric Disease designations, and both CUTX-101 and AAV-ATP7A have received FDA Orphan Drug designation previously. Additionally, the European Medicines Agency previously granted Orphan Drug designation to CUTX-101.

Author: Rare Daily Staff

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