Relief Therapeutics announced positive results from its pivotal bioequivalence clinical study evaluating RLF-OD032, an innovative highly concentrated liquid formulation of sapropterin dihydrochloride for treating phenylketonuria (PKU). The study achieved its primary pharmacokinetic endpoints, demonstrating bioequivalence to KUVAN Powder, the FDA-approved reference drug.
Study Design and Results
The randomized, open-label, two-way crossover study compared the pharmacokinetics of RLF-OD032 administered without water against the reference product administered with water under fed conditions. RLF-OD032 was well tolerated with no serious adverse events reported. The results are based on a pre-database lock analysis and await final data verification.
"We are extremely pleased to have advanced RLF-OD032 from concept to clinical validation in just three years, demonstrating its bioequivalence and confirming its potential as the first ready-to-use liquid sapropterin formulation," said Giorgio Reiner, chief scientific officer of Relief.
Addressing Treatment Limitations
RLF-OD032 offers a novel approach to PKU management by addressing key limitations of current sapropterin therapies that must be mixed with large volumes of water. As a ready-to-use, highly concentrated liquid, RLF-OD032 can be administered directly without water, providing a portable, low-volume, and patient-friendly alternative.
The formulation delivers up to a 100-fold reduction in dose volume compared to existing treatments, which is expected to improve adherence, optimize outcomes, and enhance quality of life for children and adults living with PKU. This advancement aims to enhance compliance, particularly among pediatric patients who often struggle with the high volumes associated with existing sapropterin treatments.
Regulatory Timeline
Relief plans to proceed with final data verification and completion of chemistry, manufacturing, and controls (CMC) activities in preparation for submission of a 505(b)(2) New Drug Application. The NDA is expected to be filed in early 2026, seeking U.S. marketing approval for PKU treatment, and will be subject to a 10-month FDA review under the 505(b)(2) pathway.
If approved, RLF-OD032 would be the first and only portable, ready-to-use liquid formulation of sapropterin dihydrochloride, with pending patent protection extending through at least 2043.
Disease Background
Phenylketonuria is a genetic disorder caused by a deficiency of the enzyme needed to break down phenylalanine, leading to toxic buildup from consuming foods containing protein or aspartame. Without treatment, PKU can cause severe neurological and developmental issues. The standard treatment involves a lifelong phenylalanine-restricted diet supplemented with amino acid-based, phenylalanine-free medical foods. However, this diet is highly restrictive and often creates barriers to social interaction, limiting compliance and increasing the risk of poor disease management.
