Glycerol phenylbutyrate, sold under the brand name Ravicti, is a nitrogen-binding agent medication used for chronic management of certain urea cycle disorders. The medication reduces the harmful buildup of ammonia in the body. It functions as a prodrug of phenylbutyric acid, which conjugates with glutamine to form phenylacetylglutamine, facilitating ammonia excretion via the kidneys
It was developed by Hyperion Therapeutics based on the existing medication sodium phenylbutyrate, and received FDA approval in February 2013.
Glycerol phenylbutyrate is indicated for chronic management of people with urea cycle disorders who cannot be managed by dietary protein restriction and/or amino acid supplementation alone.
While GPB is the subject of several patents related to its synthesis, formulation, and therapeutic monitoring, the core patent covering its composition and use in treating UCDs is US 5,968,979. Subsequent patents build on this foundation, focusing on manufacturing improvements, dosing methods, and related applications. Below is a summary of key issued US patents explicitly addressing GPB's use in UCDs, based on patent database records. Note that patents often cover broader nitrogen retention disorders, including UCDs as a primary indication.
Additional Notes Patent Expiry: US 5,968,979 expired in 2018, potentially allowing generic GPB formulations by late 2025. Later patents (e.g., US 9,914,692) extend protection for synthesis methods until ~2035âÂÂ2038. Related Patents: International patents (e.g., WO 2015/063659) and pending US applications (e.g., US 2021/0114996 for RNA-modulating therapies) mention GPB but are not issued US patents. Clinical Context: These patents supported trials showing GPB reduces ammonia by ~30% compared to sodium phenylbutyrate, leading to FDA approval for patients âÂÂ¥2 months.
Scope and Expiry: US 5,968,979 expired in 2018, aligning with the entry of generic GPB formulations expected by late 2025. Later patents (e.g., US 9,914,692) extend protection for manufacturing processes, potentially affecting generics until around 2035-2038. Related but Non-US or Pending: International equivalents (e.g., WO 2015/063659 for GPB synthesis) and US applications (e.g., US 2021/0114996 for RNA-modulating therapies in UCDs mentioning GPB) exist but are not issued US patents. Clinical Context: These patents supported pivotal trials (e.g., phase 3 studies showing GPB reduces ammonia by 30% vs. sodium phenylbutyrate) leading to FDA approval for all ages âÂÂ¥2 months.
Hyperion has been criticized for setting a high price for the drug. The price was set at US$250,000âÂÂ290,000. In 2014, the drug generated $30.8 million in net sales, far behind the older and less expensive Buphenyl ($113.6 million in sales).