NICE Approves Sparsentan for Kidney Disease Treatment

The National Institute for Health and Care Excellence has recommended sparsentan (Filspari, Vifor Pharma) for treating primary immunoglobulin A nephropathy in adults.

The recommendation reverses NICE’s February decision to reject NHS funding for the drug. The regulator had previously said available evidence did not demonstrate value for money.

The manufacturer provided additional analyses and agreed to a price discount, leading to the positive recommendation.

Clinical Benefits Demonstrated

Sparsentan reduces urine protein-to-creatinine ratio (UPCR) more effectively than standard treatment. The drug may also better maintain kidney function, NICE said. 

In its final draft guidance, the regulator recommended sparsentan for IgAN patients with a urine protein excretion of 1.0 g/day or more, or a UPCR of 0.75 g/g or higher. 

Treatment should cease after 36 weeks if a patient’s UPCR remains at or above 1.76 g/g and has not reduced by at least 20%.

Significant Patient Impact

IgAN affects more than 18,000 people in England. It ranks among the most common causes of chronic kidney disease and kidney failure. 

Over 4200 people with chronic kidney disease could benefit from NICE’s recommendation.

Standard care for IgAN includes angiotensin-2 receptor blockers such as irbesartan.

Mechanism of Action

Sparsentan works by blocking the receptors for two hormones —endothelin-1 and angiotensin II — that cause kidney damage. By blocking these receptors, the drug reduces the amount of proteinuria and slows down the progression of kidney damage. 

Clinical trial evidence has shown that sparsentan reduces UPCR more than irbesartan. Evidence also suggests that sparsentan is better at maintaining kidney function than irbesartan, but this was uncertain, NICE explained.

PROTECT Study Results

The regulator’s recommendation was informed by the outcome of the PROTECT study. The double-blind, randomised, active-controlled, phase 3 trial included patients aged 18 years or older with biopsy-proven primary IgAN and proteinuria of at least 1.0 g daily despite maximised renin-angiotensin system inhibition for a minimum of 12 weeks.

Patients were randomly assigned to either receive 400 mg of oral sparsentan or 300 mg of oral irbesartan, both taken once daily.

The sparsentan group showed slower rates of estimated glomerular filtration rate (eGFR) decline. At 36 weeks, sparsentan had significantly reduced proteinuria, a reduction that continued throughout the study. 

At 110 weeks, proteinuria, as determined by the change from baseline in UPCR, was 40% lower in the sparsentan group compared with irbesartan patients. 

The composite kidney failure endpoint was reached by 9% of patients in the sparsentan group compared with 13% of those in the irbesartan group. 

The researchers concluded that treatment with sparsentan versus maximally titrated irbesartan in patients with IgAN resulted in significant reductions in proteinuria and preservation of kidney function.

Treatment Advantages

Sparsentan is taken as a once-daily tablet for long-term use. This differs from targeted-release budesonide, which is limited to 9 months’ duration.

NICE said it expected the treatment to reduce NHS pressure by preventing or delaying progression to end-stage renal disease requiring dialysis or transplant.

Helen Knight, director of medicines evaluation at NICE, highlighted the limited treatment options available for the disease. She said that sparsentan offered long-term benefits to patients and “could make a huge difference to people’s lives by delaying kidney failure”. 

Fiona Loud, policy director at Kidney Care UK, welcomed the guidance. She noted that IgAN typically affects younger patients, disrupting lives when people have young families or are starting careers.

“We’re pleased that this new treatment for IgAN will now be an option for patients who need it,” Loud said.

Dr Rob Hicks is a retired NHS doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online. He is based in the UK.