Novel Agents Promising in Pruritus, Rare Metabolic Disease, and More

Research on treatment for APOL1-mediated kidney disease and kidney troubles in COVID-19 patients, as well as DIAMOND trial data, were highlights at the 2022 National Kidney Foundation Spring Clinical Meetings. Below are a few more noteworthy studies.

Pruritus Treatment for Dialysis Patients

Treatment with difelikefalin (Korsuva) significantly reduced pruritus within 12 weeks, according to a post-hoc analysis of the KALM-1 & KALM-2 phase III trials.

Pooling data on maintenance hemodialysis patients, 40.6% of difelikefalin-treated patients with severe pruritus at baseline had no or mild pruritus at week 12 compared with 26.4% of placebo patients (P<0.01), reported Daniel Weiner, MD, of Tufts University in Boston, and colleagues.

Participants in the studies had an average 24-hour Worst Itching Intensity Numerical Rating Scale score above 4. Severe pruritus was defined as a score of 7 or higher out of 10. They received IV difelikefalin 0.5 mcg/kg three times per week for 12 weeks.

Weiner's group also evaluated data from the CR845-CLIN3105 trial, and found that 62% of patients who reported severe pruritus at baseline had none or only mild pruritus by week 12, "which may reflect potential real-world effectiveness," the researchers wrote.

Difelikefalin is a selective kappa opioid receptor agonist that was FDA approved in August 2021, and is the first treatment indicated for adults on hemodialysis with moderate-to-severe pruritus.

ILLUMINATE-A Findings

Long-term treatment with subcutaneous lumasiran (Oxlumo) significantly reduced urinary oxalate (UOx) excretion in patients with primary hyperoxaluria type 1, according to results from the ongoing phase III ILLUMINATE-A trial.

In the 39-participant trial, 83% of children and adults on 6 months of lumasiran, followed by an additional on-treatment lumasiran extension phase, achieved 24-hour UOx excretion of 1.5x ULN or less by month 24 versus 61% of patients who first received 6 months of placebo followed by lumasiran during the extension phase, reported John Lieske, MD, of the Mayo Clinic in Rochester, and colleagues.

Both groups saw stable eGFRs, and average reductions from baseline in plasma oxalate were 56% and 61%, respectively, by month 24.

In the lumasiran-lumasiran group, kidney stone event rates dropped from 3.19/person-year during the 12 months prior to 0.80/person-year. In the placebo-lumasiran group, kidney stone event rate dropped from 0.54/person-year to 0.28/person-year.

Lumasiran was generally safe and well-tolerated, with most adverse events ranked as mild, such transient injection-site reactions including erythema, pain, pruritus, and swelling.

Trial participants were children and adults, ages 6 and older, with UOx excretion of 0.7 mmol/24h/1.73² or higher, confirmed AGXT mutations, and an eGFR of 30 mL/min/1.73² or higher. The ILLUMINATE-B trial will evaluate the agent in young children and infants.

Lumasiran is a liver-directed RNAi therapeutic that acts by decreasing hepatic oxalate production via glyoxylate production inhibition. FDA approved in November 2020, lumasiran was the first drug indicated for patients with primary hyperoxaluria type 1, characterized by hepatic of reproduction of oxalate.

Real-World Lokelma Use

Among >1,000 real-world outpatients with hyperkalemia treated with sodium zirconium cyclosilicate (Lokelma), 35% received long-term therapy (>90 days), according to the RECOGNIZE I study, while 65% received short-term sodium zirconium cyclosilicate therapy (≤90 days).

During a 6-month follow-up period, 33% fewer patients on long-term therapy were hospitalized with hyperkalemia (10% vs 15% on short-term), and long-term therapy was tied to a 23% reduced risk of all-cause hospitalization (22% vs 29%), reported Abiy Agiro, PhD, of AstraZeneca in Wilmington, Delaware.

Similar trends were seen when separating out patients who didn't have end-stage renal disease (ESRD), Agiro stated.

"This suggests that long-term sodium zirconium cyclosilicate therapy may be associated with reduced hyperkalemia-related hospitalizations and emergency department visits, which may lead to a reduction in hyperkalemia-related healthcare costs," the researchers wrote of the claims database-driven study.

They found that some predictors of long-term sodium zirconium cyclosilicate use included living in the Western U.S. and having stage 3 chronic kidney disease versus no CKD. Some factors associated with short-term therapy included being insured with Medicaid. Specifically in non-ESRD patients, having liver disease was associated with short-term treatment.