NICE backs first disease-modifying drug for ARG1 deficiency

An enzyme replacement therapy developed by Immedica, the first drug for the inherited metabolic disorder arginase-1 (ARG1) deficiency that can alter the course of the disease, has been cleared for NHS use in the UK.

Loargys (pegzilarginase), which is administered as a once-weekly intravenous infusion or subcutaneous injection, replaces the arginase enzyme responsible for the removal of toxic waste such as ammonia via the kidneys in urine that doesn't work correctly in people with the rare disease.

The defect means that high levels of ammonia and other toxic substances build up in the body, causing a range of symptoms, including progressive spasticity of the legs, developmental delays, physical and intellectual disability, and seizures. The disease is ultra-rare, with only around 20 cases identified in England, according to reimbursement authority NICE.

Final draft guidance, which is expected to be finalised in March, recommends Loargys as an option for people aged two years and over living with ARG1 deficiency.

At the moment, the disorder is managed using dietary protein restrictions, essential amino acid supplementation, and ammonia-lowering drugs such as sodium phenylbutyrate or sodium benzoate, with other drugs used to tackle symptoms, such as epilepsy medications for seizures.

Clinical trial evidence from the phase 3 PEACE trial in 32 subjects showed that adding Loargys to usual treatment reduces levels of arginine in the blood by almost 80% over 24 weeks, and UK patient advocacy organisation Metabolic Support said the recommendation "represents a potentially significant step forward for families affected by this rare condition."

NICE has agreed a confidential discount with Immedica on Loargys' list price, which is £4,690 ($6,363) per 2 mg vial. According to its labelling, the recommended starting dose of the therapy is 0.1 mg/kg, which can be increased in 0.05 mg/kg increments to achieve the desired efficacy, and the average cost per year – before discounts – is expected to be around £33,000.

"It's fantastic news for patients and their loved ones that this pioneering, first-in-class treatment will now be available on the NHS to help manage some of the complex, challenging symptoms of this ultra-rare condition," said Jack Turner, deputy director of medicines negotiation and access at NHS England.

"The novel commercial deal for pegzilarginase will offer fresh hope, unlocking access to an innovative treatment for dozens of people affected by this condition – many of them children – and, while not a cure, it could make a really positive difference to their everyday lives," he added.

Earlier this month, Stockholm, Sweden-based Immedica also reported new clinical data with Loargys in the phase 3 CAEB1102-301A trial, showing that the drug was also effective at reducing arginine levels in ARG1 deficiency patients aged below two.

The company's head of rare metabolic diseases research, Dr Mattias Rudebeck, said at the time that earlier treatment with the drug "not only has the potential to alter the trajectory of disease, but also to give families greater confidence about the future."