Phenylketonuria - Pipeline Insight, 2024

This “Phenylketonuria- Pipeline Insight, 2024” report provides comprehensive insights about 18+ companies and 20+ 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.

Geography Covered

• Global coverage

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. This enzymatic failure results in high blood concentration of Phe, which is toxic to the central nervous system. The natural history of PKU consists in a progressive irreversible encephalopathy, the most common outcome is severe mental retardation and other neurological complications, such as epilepsy, tremor, hyperactivity, autistic features, and behavioral problems, such as aggressiveness, stereotypy, anxiety, and phobias, among others. ‘‘Mousy odor,’’ eczema, and hypopigmentation of hair, skin, and iris are also characteristic. From the early 60s in developed countries, this disease is routinely detected through newborn screening (NBS), which allows early treatment and prevention of neurological damage. PKU diagnosis is achieved soon after birth by neonatal screening in most developed countries. In the countries where expanded newborn screening has been adopted, PKU is diagnosed by Phe and Tyr's evaluation in neonatal dried blood spot (DBS) using tandem mass spectrometry. Virtually, 100% of PKU subjects should be identified. The risk of false-negative has become more pressing with early postnatal discharge from the hospital for mothers and term infants. In such cases, Phe/Tyr ratio evaluation increase the sensitivity and positive predictive value of the test, avoiding the false-negative and lowering false-positive risk. The Conventional way to manage phenylketonuria is Nutritional therapy in which patient has to balance the amount of Daily Phe, Tyr, Protein, and Energy at the Beginning of the Nutritional Therapy. For different age groups different amount of daily Daily Phe, Tyr, Protein, and Energy is recommended.

Phenylketonuria- Pipeline Insight, 2024 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 II, 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 (PTC923) is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, an enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products. Results from a Phase II clinical trial of CNSA-001 demonstrated significant and clinically relevant reductions in phenylalanine levels compared to current first-line treatment. Previous preclinical and healthy volunteer studies showed that an oral dose of CNSA-001 increased target tissue and plasma tetrahydrobiopterin more effectively than equivalent oral doses of sapropterin dihydrochloride. Since sepiapterin is a more stable molecule and is transported more efficiently across cells, it has the potential to be more effective than Kuvan in boosting PAH activity, reducing phenylalanine levels, and lessening symptoms in PKU patients. In May 2020, PTC Therapeutics announced that it agreed to acquire Censa Pharmaceuticals, focused on developing CNSA-001 (sepiapterin). Sepiapterin is currently being investigated in Phase III stage of development for the treatment of Phenylketonuria.

SYNB1618: Synlogic SYNB1618 is an orally administered Synthetic Biotic TM medicines being developed as potential treatments for phenylketonuria (PKU). It is an engineered strain of the microorganism E. coli Nissle that encodes phenylalanine ammonia lyase (PAL), an enzyme that breaks down Phe. It is intended to address the needs of patients of all age groups through the consumption of Phe in the gastrointestinal tract, which has the potential to lower blood Phe levels and enable the consumption of more natural protein in the diet. SYNB1618 has received both Orphan Drug and Fast Track designations by the US Food and Drug Administration (FDA) and orphan medicinal product designation by the European Medicines Agency. It is currently being evaluated in Phase II clinical trial to treat patientswithphenylketonuria.

HMI-102: Homology Medicine HMI-102 is an investigational gene therapy in clinical development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, and delivered via the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA). The company began the Phase I/II study of HMI-102 in 2019. The FDA held back the study over elevated liver function tests by a few months in 2022. In August 2022, the Company paused enrollment in the phe NIX gene therapy trial evaluating HMI-102, however the drug is currently active in the company’s pipeline in Phase I/II stageofdevelopment.

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. 18+ 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

This report covers around 20+ 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

• Intra-articular
• Intraocular
• Intrathecal
• Intravenous
• Ophthalmic
• Oral
• Parenteral
• Subcutaneous
• Topical
• Transdermal

Molecule Type

Products have been categorized under various Molecule types such as

• Oligonucleotide
• Peptide
• Small molecule

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

• Bio MarinPharmaceutical
• Homology Medicine
• Jnana Therapeutics
• Nestlé Health Science
• Moderna
• SOM Biotech
• Agios Pharmaceuticals
• APR Applied Pharma Research
• American Gene Technologies
• Generation Bio
• PTC Therapeutics

Key Products

• BMN 307
• HMI-103
• JNT 517
• CDX 6114
• mRNA-3283
• SOM1311

Research programme: phenylalanine hydroxylate stabilizers- APR OD031
Research programme: phenylketonuria therapeutic lentivirus- Research programme: gene therapies

• Sepiapterin

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