NICE has recommended maralixibat for cholestatic pruritus caused by Alagille syndrome in people aged two months and older, following a final draft guidance assessment.

NHS recommendation addresses debilitating itching

NICE has issued final draft guidance recommending Mirum Pharmaceuticals’ maralixibat oral solution for treating cholestatic pruritus associated with Alagille syndrome (ALGS) in people aged two months and older.

The recommendation covers use within the NHS in England and Wales, with maralixibat intended as an add-on to standard first-line treatments when these have not worked well enough. These treatments include bile acid sequestrants, ursodeoxycholic acid, rifampicin and opioid receptor antagonists.

According to Mirum, maralixibat is the only medicine recommended by NICE specifically for cholestatic pruritus associated with ALGS.

Alagille syndrome is a rare genetic disorder in which abnormalities in the bile ducts cause bile acids to accumulate in the liver. This can lead to inflammation, liver injury and progressive liver disease. The condition can also affect other organs, including the heart and kidneys.

Cholestatic pruritus, or severe itching associated with impaired bile flow, is among the most common and debilitating symptoms of ALGS. It can disrupt sleep, affect daily activities and significantly reduce quality of life. Severe itching is also among the most common indications for liver transplantation in people with the condition.

Michelle Wilkins, head of children and families service at Liver UK, said: “Families living with Alagille syndrome know how devastating the itch can be – children scratch until they bleed, struggle to sleep, and their daily lives are dominated by discomfort. NICE’s recommendation of maralixibat is an important moment for the UK patient community, offering a potential option for a debilitating condition and recognising the urgent need for better treatment options for families affected.”

Clinical evidence supports the recommendation

NICE’s recommendation is based primarily on the ICONIC study, supported by longer-term data from the MERGE study.

ICONIC was a Phase 2b, placebo-controlled, randomised drug withdrawal study involving 31 children with ALGS, with a mean age of 5.4 years. Participants initially received maralixibat for 18 weeks before being randomised to continue treatment or switch to placebo for four weeks. All participants subsequently received maralixibat for the remainder of the 48-week study.

Treatment was associated with clinically relevant and statistically significant reductions in serum bile acid levels and pruritus compared with baseline at Weeks 18 and 48. During the randomised withdrawal period, serum bile acid levels and itching differed significantly between participants who switched to placebo and those who continued maralixibat.

Longer-term follow-up from MERGE found that improvements in clinical outcomes, including itching, serum bile acid levels and growth, persisted through seven years of treatment.

Maralixibat was generally well tolerated in ICONIC. Most treatment-emergent adverse events were mild or moderate, with diarrhoea and abdominal pain among the most frequently reported. The longer-term MERGE follow-up identified no new safety concerns, according to the company.

UK access follows sustained engagement

The recommendation follows more than five years of engagement between NICE, NHS England and Mirum to support access to treatment for people with this rare condition.

Dr Tassos Grammatikopoulos, consultant in paediatric hepatology at King’s College Hospital NHS Foundation Trust, said: “Cholestatic pruritus can be one of the most challenging symptoms for children with Alagille syndrome. NICE’s recommendation of maralixibat represents an important development in clinical practice in England and Wales, providing a potentially life-changing treatment option that may help address this longstanding gap in care.”

Alexey Kutahov, senior vice-president and head of international at Mirum, said: “Today marks an important milestone for the Alagille syndrome community in England and Wales, building on last year’s acceptance of maralixibat for restricted use within NHSScotland. We are pleased that eligible patients may now have access to maralixibat through the NHS, following sustained engagement to support access for this rare disease community.”

Maralixibat is an orally administered ileal bile acid transporter inhibitor. It is approved in the UK and European Union for cholestatic pruritus associated with ALGS in patients aged two months and older. The NICE recommendation relates to its use within the NHS in England and Wales, subject to the conditions set out in the guidance and the company’s commercial arrangement.