Sentynl secures US-first approval for rare Menkes disease

The US Food and Drug Administration (FDA) has approved Zycubo (copper histidinate) subcutaneous injection, making it the first treatment to be authorised in the US for children with the rare genetic neurodegenerative disorder Menkes disease.

Based on data submitted by the market authorisation holder, US biopharma Sentynl Therapeutics, the copper replacement therapy has potential to enable patients to live longer.

Dr Tracy Beth Hoeg, PhD, Acting Director of CDER, said: “This approval marks an unprecedented advance for children with Menkes disease. 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.”

Overall survival was assessed for up to three years in two separate studies. Notably, for children who began treatment within four weeks of birth, their risk of death reduced by 78 percent compared to untreated patients.

Additionally, nearly half of early-treated patients survived beyond six years, and some survived more than 12 years. No patients in the untreated control group survived beyond six years. Individuals who began treatment beyond four weeks after birth also experienced a substantial survival benefit.

Caused by gene mutations of the copper transporter ATP7A, the X-linked recessive disease disproportionally affects more males than females. Data shows prevalence is potentially as high as 1 in 8,664 live male births, based on data from the Genome Aggregation Database (gnomAD).

Approval of copper histidinate (CUTX-101) by the FDA follows the agency’s acceptance last month of Sentynl’s NDA resubmission for the replacement therapy. That move was related to a complete response letter (CRL) from the FDA to citing observations about the biopharma company manufacturing site’s cGMP compliance.  

Last September, FDA proposed a new procedure to help expedite their reviews of rare disease clinical trials. This would see approvals accepted via one adequate and well-controlled study, alongside potentially also being based on certain robust confirmatory evidence.