Pegvaliase

{{Short description|Chemical compound}} {{Use dmy dates|date=May 2024}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | image = | alt = | caption =

| pronounce = peg val' i ase | tradename = Palynziq | Drugs.com = {{drugs.com|monograph|pegvaliase-pqpz}} | MedlinePlus = a618057 | DailyMedID = Pegvaliase | pregnancy_AU = D | pregnancy_AU_comment = <ref name="Palynziq APM summary" /><ref>{{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=12 May 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=13 May 2022 | archive-date=3 April 2022 | archive-url=https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database | url-status=live }}</ref> | pregnancy_category= | routes_of_administration = Subcutaneous | class = | ATC_prefix = A16 | ATC_suffix = AB19 | ATC_supplemental = | biosimilars =

| legal_AU = S4 | legal_AU_comment = <ref name="Palynziq APM summary">{{cite web | title=Palynziq | website=Therapeutic Goods Administration (TGA) | date=23 July 2021 | url=https://www.tga.gov.au/apm-summary/palynziq | access-date=5 September 2021 | archive-date=5 September 2021 | archive-url=https://web.archive.org/web/20210905213708/https://www.tga.gov.au/apm-summary/palynziq | url-status=live }}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = / Schedule D<ref>{{cite web | title=Palynziq Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=101536 | access-date=29 June 2022 | archive-date=29 June 2022 | archive-url=https://web.archive.org/web/20220629032328/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=101536 | url-status=live }}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Palynziq FDA label">{{cite web | title=Palynziq- pegvaliase-pqpz injection, solution | website=DailyMed | date=21 December 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6dba844a-db02-44f8-8593-ce497ed9406c | access-date=12 December 2023}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Palynziq EPAR">{{cite web | title=Palynziq EPAR | website=European Medicines Agency | date=28 January 2010 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/palynziq | access-date=22 May 2024}}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = | chemical_formula_ref = <ref>{{cite web | title=Pegvaliase | website=Inxight Drugs | url=https://drugs.ncats.io/substance/N6UAH27EUV | access-date=22 May 2024}}</ref><ref>{{cite web | title=Pegvaliase | website=GSRS | url=https://gsrs.ncats.nih.gov/ginas/app/beta/substances/N6UAH27EUV | access-date=22 May 2024}}</ref> | C = 10872 | H = 17216 | O = 3300 | N = 3040 | S = 80 | SMILES = | StdInChI = | StdInChI_comment = | StdInChIKey = | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Pegvaliase''', sold under the brand name '''Palynziq''', is a medication used for the treatment of the genetic disease phenylketonuria (PKU).<ref name="Palynziq FDA label" /><ref name=FDA2018Sub/><ref name="pmid30247930">{{cite journal | vauthors = Mahan KC, Gandhi MA, Anand S | title = Pegvaliase: a novel treatment option for adults with phenylketonuria | journal = Current Medical Research and Opinion | volume = 35 | issue = 4 | pages = 647–651 | date = April 2019 | pmid = 30247930 | doi = 10.1080/03007995.2018.1528215 | s2cid = 52813510 }}</ref> It is a phenylalanine (Phe)‑metabolizing enzyme.<ref name="Palynziq FDA label" /> Chemically, it is a pegylated derivative of the enzyme phenylalanine ammonia-lyase that metabolizes phenylalanine to reduce its blood levels.<ref name="Palynziq FDA label" />

The most common adverse events include injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus (itchy skin), nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and, diarrhea.<ref name=FDA2018Sub />

It was approved by the US Food and Drug Administration (FDA) for use in the United States in 2018.<ref name=FDA2018Sub>{{cite press release | url = https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pku-rare-and-serious-genetic-disease | title = FDA approves a new treatment for PKU, a rare and serious genetic disease | publisher = U.S. Food and Drug Administration (FDA) | date = 24 May 2018 | access-date = 12 October 2020 | archive-date = 25 July 2021 | archive-url = https://web.archive.org/web/20210725044549/https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pku-rare-and-serious-genetic-disease | url-status = dead }} {{PD-notice}}</ref> The FDA considers it to be a first-in-class medication.<ref>{{cite report | title=New Drug Therapy Approvals 2018 | website=U.S. Food and Drug Administration (FDA) | date=January 2019 | url=https://www.fda.gov/media/120357/download | format=PDF | access-date=16 September 2020 | archive-date=17 September 2020 | archive-url=https://web.archive.org/web/20200917055627/https://www.fda.gov/media/120357/download | url-status=dead }}</ref>

== Medical uses == Pegvaliase is indicated to reduce blood Phe concentrations in adults with phenylketonuria who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management.<ref name="Palynziq FDA label" />

== Adverse effects == The FDA label for pegvaliase includes a boxed warning for anaphylaxis.

Because of this risk, the FDA has instituted a Risk Evaluation and Mitigation Strategy(REMS), which requires all patients to carry auto injectable epinephrine and a wallet card.<ref>{{cite web |title=Risk Evaluation and Mitigation Strategy (REMS) Document PALYNZIQ® (pegvaliase-pqpz) REMS |url=https://www.accessdata.fda.gov/drugsatfda_docs/rems/Palynziq_2023_12_09_REMS_Full.pdf |publisher=U.S Food and Drug administration(FDA) |access-date=2 September 2025}}</ref>

== History == The safety and efficacy of pegvaliase were studied in two clinical trials in adult participants with PKU with blood phenylalanine concentrations greater than 600 μmol/L on existing management.<ref name=FDA2018Sub /> Most PKU participants in the pegvaliase trials were on an unrestricted diet prior to and during the trials.<ref name=FDA2018Sub /> The first trial was a randomized, open-label trial in participants treated with increasing doses of pegvaliase administered as a subcutaneous injection up to a target dose of either 20 mg once daily or 40 mg once daily.<ref name=FDA2018Sub /> The second trial was an 8-week, placebo-controlled, randomized withdrawal trial in participants who were previously treated with pegvaliase.<ref name=FDA2018Sub /> Participants treated with pegvaliase achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations.<ref name=FDA2018Sub />

The FDA granted approval of Palynziq to BioMarin Pharmaceutical.<ref name=FDA2018Sub />

==References== {{reflist}}

Category:Drugs acting on the gastrointestinal system and metabolism Category:Recombinant proteins Category:Orphan drugs