Less than four months after rejecting Sentynl Therapeutics and Cyprium Therapeutics’ treatment for Menkes disease, the FDA has given the partners a thumbs-up, blessing Zycubo as the first approved therapy in the U.S. for the rare neurodegenerative disorder.
The quick turnaround came after Sentynl addressed a manufacturing compliance issue that had been outlined in the FDA’s complete response letter from Sept. 30. Solana Beach, California-based Sentynl resubmitted its revised application Nov. 14 and the FDA accepted it Dec. 15, establishing a Jan. 14 decision date.
Accompanying the approval is a rare pediatric disease priority review voucher (PRV), which will be transferred to Cyprium. The Miami-based company developed the treatment on its own before inking (PDF) a $20 million transfer agreement with Sentynl in 2021. Two years later, the partners expanded the deal, with Sentynl taking full responsibility for development and commercialization of the program.
The injected copper replacement therapy, also known as copper histidinate or CUTX-101, restores copper homeostasis and maintains mineral levels in patients with the disorder.
Menkes disease is an X-linked recessive genetic condition that impairs a child’s ability to absorb and transport copper, particularly to the brain. It leads to seizures, developmental delays, intellectual disability and the failure to gain weight and grow, the companies said. It also leads to issues with the bladder, bowel, bones, muscles and the nervous and vascular systems.
Children develop symptoms in infancy and typically do not live beyond 3 years. Menkes affects roughly one in every 100,000 to 250,000 live births and is more common in boys.
Paving the way for the FDA nod were two single-arm clinical trials in which 66 patients were treated for up to three years. Overall survival was assessed by comparing results among treated patients to untreated patients from external control groups, according to the FDA.
Median overall survival was 177.1 months for those on Zycubo compared to 17.6 months for the external control group, according to data provided by Sentynl.
“The company demonstrated a large improvement in overall survival compared with untreated patients, using an innovative trial design that addressed the challenges of studying an ultra-rare disease,” Tracy Beth Hoeg, M.D., Ph.D., acting director of the Center for Drug Evaluation and Research, said in a release.
Side effects reported with Zycubo include infections, respiratory problems, seizures, vomiting, fever, anemia and injection site reactions. Because copper can accumulate in the body, patients receiving Zycubo should be closely monitored for potential toxicity, the FDA said.
Cyprium is a subsidiary of Florida-based Fortress Biotech, which was established in 2013 to evaluate and acquire assets that have been de-risked with strong clinical data. Fortress creates subsidiaries and forms partnerships with other companies to develop the assets.
Fortress facilitated the 2024 FDA approvals of Checkpoint Therapeutics’ skin cancer therapy Unloxcyt and Journey Medical and Dr. Reddy’s rosacea treatment Emrosi. In March of last year, Sun Pharma bought out dermatology specialist Checkpoint in a deal worth up to $416 million.
In addition to the PRV, Cyprium will receive milestone payments and royalties on sales of Zycubo.
“We believe that our business model has demonstrated measurable success and continued execution across the portfolio,” Lindsay Rosenwald, M.D., Fortress’ CEO, said in a release. “We look forward to the potential achievement of additional upcoming milestones across our extensive pipeline of commercial and clinical-stage assets.”
Sentynl also is a subsidiary, answering to India-based Zydus Lifesciences.