Phenylketonuria- Pipeline Insight, 2025

This “Phenylketonuria- Pipeline Insight, 2025” report provides comprehensive insights about 20+ companies and 25+ pipeline drugs in Phenylketonuria pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Phenylketonuria: Understanding

Phenylketonuria: Overview

Phenylketonuria as known as PKU is a metabolic disorder that can adversely affect the body’s natural homeostatic or steady state and lead to chemical imbalances and severe pathological conditions. Phenylketonuria is such an example in which the normal conversion of the dietary amino acid phenylalanine to tyrosine is blocked. The resulting build-up of phenylalanine and its metabolites in young patients produces a number of severe side effects including intellectual impairment and cutaneous changes. Phenylketonuria belongs to a class of aminoacidopathies termed toxic accumulation IEMs, in which the accumulation of an amino acid or its metabolite is toxic. It is an inborn error of amino acid metabolism caused by a deficient activity of phenylalanine hydroxylase (PAH), an enzyme that converts essential amino acid phenylalanine (Phe) into tyrosine (Tyr), a nonessential amino acid that becomes essential in PKU.

Under normal circumstances, Phenylalanine (Phe) coming from the dietary contribution and endogenous protein is metabolized to Tyrosine (Tyr) by PAH with the concourse of Tetrahydrobiopterin, oxygen, and iron. In addition, Phe is converted by the action of Phe-decarboxylase to Phenylethyamine. However, patients with PKU lack PAH, and as a consequence Phe plasma levels increase achieving toxic levels in the brain. Phe in excess is converted into Phenylpyruvate, Phenylacetate, and Phenyllactate that are highly toxic for the brain. Phe competes with the other large neutral amino acids (LNAA) for the same L-type carrier (LAT-1) to cross the blood-brain barrier (BBB). In addition, circulating Tyr decreases, and subsequently, the synthesis of metabolites such as Dopamine, Noradrenaline, and Adrenaline diminishes. The consequence of these metabolic alterations is protracted brain damage. PAH Phenylalanine hydroxylase, LNAA L-neutral amino acids, LAT1 amino acid transporter across the blood-brain barrier, BBB blood-brain barrier, Phe Phenylalanine.

PKU is typically diagnosed shortly after birth through neonatal screening, primarily using tandem mass spectrometry to evaluate Phe and Tyr levels in dried blood spots, which enhances sensitivity and reduces false negatives/positives. Traditional methods like the Guthrie test, while simple and cost-effective, are being replaced by automated, quantitative techniques such as fluorimetric testing for greater accuracy and efficiency.

Phenylketonuria (PKU) is conventionally managed through nutritional therapy, requiring age-specific regulation of Phe, Tyr, protein, and energy intake. Additional treatments include large neutral amino acid supplementation to limit brain phenylalanine, enzyme replacement therapy, and BH4 (tetrahydrobiopterin) therapy. Sapropterin dihydrochloride (Kuvan), a synthetic BH4 form, has shown efficacy in some PKU patients with specific PAH gene mutations. . Clinical trials have shown that a subset of ‘classical’ PKU children respond to BH4 therapy, dependent upon their PAH gene mutation(s).

'Phenylketonuria- Pipeline Insight, 2025' report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Phenylketonuria pipeline landscape is provided which includes the disease overview and Phenylketonuria treatment guidelines. The assessment part of the report embraces, in depth Phenylketonuria commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Phenylketonuria collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights

The companies and academics are working to assess challenges and seek opportunities that could influence Phenylketonuria R&D. The therapies under development are focused on novel approaches to treat/improve Phenylketonuria.

Phenylketonuria Emerging Drugs Chapters

This segment of the Phenylketonuria report encloses its detailed analysis of various drugs in different stages of clinical development, including phase III, II, II/III I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

Phenylketonuria Emerging Drugs

Sepiapterin: PTC Therapeutics

Sepiapterin (formerly PTC923), an oral formulation of synthetic sepiapterin, has a dual mechanism of action to increase activity of the phenylalanine hydroxylase (PAH) enzyme. First, sepiapterin is a precursor compound that is rapidly absorbed and converted intracellularly to tetrahydrobiopterin (BH4), a critical cofactor of PAH. Sepiapterin also has an independent chaperone effect, protecting against PAH misfolding to enhance the enzyme function. Through this dual mechanism of action, sepiapterin effectively reduces blood phenylalanine (Phe) levels and has the potential to treat the broad range of PKU patients. Currently the drug is in been registered for Phenylketonuria (PKU).

JNT-517: Otsuka Pharmaceutical

JNT-517 is a selective small molecule inhibitor of the Phe transporter SLC6A19 that has the potential to be a first-in-class oral therapy used to treat any person with PKU, regardless of age or genotype. JNT-517 acts at a novel, cryptic allosteric site to block kidney reabsorption of Phe and offers a promising new approach to reduce blood. . Currently the drug is in Phase III for Phenylketonuria (PKU).

RLF OD032: Relief Therapeutics Holding

RLF-OD032, an innovative and highly concentrated liquid formulation of sapropterin dihydrochloride, is designed to lower blood phenylalanine in adult and pediatric PKU patients. It offers a more patient-friendly solution by significantly reducing the volume of medication required compared to current formulations. This advancement aims to enhance compliance, particularly among pediatric patients, who often struggle with the high volumes associated with existing sapropterin treatments. If approved, RLF-OD032 would be the first and only portable, ready-to-use liquid formulation of sapropterin dihydrochloride. Currently the drug is in Phase I Stage of its development for the treatment of Phenylketonuria (PKU).

Phenylketonuria: Therapeutic Assessment

This segment of the report provides insights about the different Phenylketonuria drugs segregated based on following parameters that define the scope of the report, such as:

Major Players in Phenylketonuria

There are approx. 20+ key companies which are developing the therapies for Phenylketonuria. The companies which have their Phenylketonuria drug candidates in the most advanced stage, i.e. Phase III include, PTC Therapeutics.

Phases

The report covers around 25+ products under different phases of clinical development like

• Late stage products (Phase III)
• Mid-stage products (Phase II)
• Early-stage product (Phase I) along with the details of
• Pre-clinical and Discovery stage candidates
• Discontinued & Inactive candidates

Route of Administration

Phenylketonuria pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Intravenous
• Subcutaneous
• Oral
• Intramuscular

Molecule Type

Products have been categorized under various Molecule types such as

• Monoclonal antibody
• Small molecule
• Peptide

Product Type

Drugs have been categorized under various product types like Mono, Combination and Mono/Combination.

Phenylketonuria: Pipeline Development Activities

The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Phenylketonuria therapeutic drugs key players involved in developing key drugs.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Phenylketonuria drugs.

Phenylketonuria Report Insights

• Phenylketonuria Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

Phenylketonuria Report Assessment

• Pipeline Product Profiles
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing Phenylketonuria drugs?
• How many Phenylketonuria drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Phenylketonuria?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Phenylketonuria therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for Phenylketonuria and their status?
• What are the key designations that have been granted to the emerging drugs?

Key Players

• PTC Therapeutics
• BioMarin Pharmaceutical
• Otsuka Pharmaceutical
• Relief Therapeutics Holding
• BioMarin Pharmaceutical
• Tessera Therapeutics

Key Products

• Sepiapterin
• Pegvaliase
• JNT-517
• RLF OD032
• BMN 390
• Gene writers

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