First-in-class medication

{{Short description|Term for a groundbreaking pharmaceutical drug}}

A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition.{{Cite journal|last1=Lanthier|first1=Michael|last2=Miller|first2=Kathleen L.|last3=Nardinelli|first3=Clark|last4=Woodcock|first4=Janet|date=2013-08-01|title=An Improved Approach To Measuring Drug Innovation Finds Steady Rates Of First-In-Class Pharmaceuticals, 1987–2011|url=https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2012.0541|journal=Health Affairs|volume=32|issue=8|pages=1433–1439|doi=10.1377/hlthaff.2012.0541|pmid=23918488|issn=0278-2715|url-access=subscription}}{{Dead link|date=March 2023 |bot=InternetArchiveBot |fix-attempted=yes }} While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medications and reports on them annually, first-in-class is not considered a regulatory category. Although many first-in-class medications qualify as breakthrough therapies, Regenerative Medicine Advanced Therapies and/or orphan drugs, first-in-class status itself has no regulatory effect.

Examples

class="wikitable sortable"

|+

!Drug

!Class

!Targeted conditions

!Year approved

(FDA)

!Year approved

(EMA)

Inotuzumab ozogamicin

(Besponsa)

|Anti-CD22 monoclonal antibody-drug conjugate

|Relapsed or refractory B cell precursor acute lymphoblastic leukemia{{Cite web|title=BESPONSA 1 mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC) - (emc)|url=https://www.medicines.org.uk/emc/medicine/33679|access-date=2021-07-01|website=www.medicines.org.uk}}

|2017

|

Tagraxofusp

(Elzonris)

|Interleukin 3-diphtheria toxin fusion protein targeting plasmacytoid dendritic cells

|Blastic plasmacytoid dendritic cell neoplasm

|2018

|2021

Midostaurin

(Rydapt)

|Multi-target tyrosine kinase inhibitor not inhibited by the D816V cKit mutation

|Systemic mastocytosis, myelodysplastic syndrome, acute myeloid leukemia{{Cite web|title=Rydapt: Uses, Dosage, Side Effects, Warnings|url=https://www.drugs.com/rydapt.html|access-date=2021-07-01|website=Drugs.com|language=en}}

|2017

|2017{{Cite web |title=Rydapt {{!}} European Medicines Agency |url=https://www.ema.europa.eu/en/medicines/human/EPAR/rydapt |access-date=2024-01-16 |website=www.ema.europa.eu}}

Teprotumumab

(Tepezza)

|Anti-IGF-1R monoclonal antibody

|Graves' ophthalmopathy{{Cite web|last=Office of the Commissioner|date=2020-03-24|title=FDA approves first treatment for thyroid eye disease|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-thyroid-eye-disease|archive-url=https://web.archive.org/web/20200828223737/https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-thyroid-eye-disease|url-status=dead|archive-date=August 28, 2020|access-date=2021-07-01|website=FDA|language=en}}

|2020

|

Romosozumab

(Evenity)

|Anti-sclerostin monoclonal antibody

|Osteoporosis{{Cite journal|last=Center for Drug Evaluation and Research|date=2020-01-24|title=New Drug Therapy Approvals 2019|url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019|archive-url=https://web.archive.org/web/20200502164101/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019|url-status=dead|archive-date=May 2, 2020|journal=FDA|language=en}}

|2019

|2019

Ocrelizumab

(Ocrevus)

|Anti-CD20 monoclonal antibody

|Multiple sclerosis{{Cite web|title=Ocrevus (ocrelizumab) Injection|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761053Orig1s000TOC.cfm|archive-url=https://web.archive.org/web/20200327023211/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761053Orig1s000TOC.cfm|url-status=dead|archive-date=March 27, 2020|access-date=2021-07-01|website=www.accessdata.fda.gov}}

|2017

|2018

Ivosidenib

(Tibsovo)

|Small molecule inhibitor of isocitrate dehydrogenase 1

|Acute myeloid leukemia, cholangiocarcinoma{{Cite web|title=Search Orphan Drug Designations and Approvals|url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=481515|archive-url=https://web.archive.org/web/20210625094256/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=481515|url-status=dead|archive-date=June 25, 2021|access-date=2021-07-01|website=www.accessdata.fda.gov}}

|2018

|2023

Bempedoic acid

(Nexletol)

|Adenosine triphosphate-citrate lyase inhibitor

|Hypercholesterolemia{{Cite web|title=DailyMed - NEXLETOL- bempedoic acid tablet, film coated|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=88d06d89-a3da-40b4-b273-8f4f7d56c4c9|access-date=2021-07-01|website=dailymed.nlm.nih.gov}}

|2020

|2020

Tafamidis

(Vyndaqel, Vyndamax)

|Transthyretin chaperone (stabilizer)

|Familial amyloid polyneuropathy and other transthyretin amyloidoses{{Cite web|title=Tafamidis Monograph for Professionals|url=https://www.drugs.com/monograph/tafamidis.html|access-date=2021-07-01|website=Drugs.com|language=en}}

|2011

|2019

Voxelotor

(Oxbryta)

|Hemoglobin oxygen affinity modulator

|Sickle cell disease{{Cite web|title=DailyMed - OXBRYTA- voxelotor tablet, film coated|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c557fac-29ec-483f-b691-8a935d4decc3|access-date=2021-07-01|website=dailymed.nlm.nih.gov}}

|2019

|

Lonafarnib

(Zokinvy)

|Farnesyltransferase inhibitor

|Hutchinson-Gilford progeria syndrome{{Cite web|title=DailyMed - ZOKINVY- lonafarnib capsule|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=956a142f-35d6-4fe3-8aef-7e4878d275ed|access-date=2021-07-01|website=dailymed.nlm.nih.gov}}

|2020

|2022

Dupilumab

(Dupixent)

|Interleukin-4 receptor alpha subunit inhibitor

|Asthma, atopic dermatitis, allergic diseases{{Cite web|title=DailyMed - DUPIXENT- dupilumab injection, solution|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=595f437d-2729-40bb-9c62-c8ece1f82780|access-date=2021-07-01|website=dailymed.nlm.nih.gov}}

|2017

|

Lasmiditan

(Reyvow)

|Selective 5-HT1F serotonin receptor agonist

|Migraine{{Cite web|title=DailyMed - Search Results for Lasmiditan|url=https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Lasmiditan|access-date=2021-07-01|website=dailymed.nlm.nih.gov}}

|2019

|2022

Tazemetostat

(Tazverik)

|Selective EZH2 inhibitor

|Epithelioid sarcoma{{Cite web|title=Tazemetostat Monograph for Professionals|url=https://www.drugs.com/monograph/tazemetostat.html|access-date=2021-07-01|website=Drugs.com|language=en}}

|2020

|

Tirzepatide

(Mounjaro)

|GLP-1 and GIP activator

|adult type 2 diabetes{{Cite web|title= FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes|url=https://www.fda.gov/news-events/press-announcements/fda-approves-novel-dual-targeted-treatment-type-2-diabetes|archive-url=https://web.archive.org/web/20220513192349/https://www.fda.gov/news-events/press-announcements/fda-approves-novel-dual-targeted-treatment-type-2-diabetes|url-status=dead|archive-date=May 13, 2022|access-date=2022-06-30|website=fda.gov|date=13 May 2022 |language=en}}

|2022

|2022

Controversy

= Safety =

By definition, a first-in-class drug does not have the safety evidence from analogous products that not-first-in-class drugs would have. However, a study investigating recalls and warnings in relation to first-in-class drugs approved between 1997 and 2012 by Health Canada has found that first-in-class drugs actually have a more favourable benefit-to-harm ratio.{{Cite journal|last=Lexchin|first=Joel|date=November 2016|title=How Safe and Innovative Are First-in-Class Drugs Approved by Health Canada: A Cohort Study|journal=Healthcare Policy|volume=12|issue=2|pages=65–75|issn=1715-6572|pmc=5221712|pmid=28032825}}

= Economics =

First-in-class drugs are often seen as commercially more attractive as they may tap into a market segment that has hitherto been underserved, but this may be illusory.{{Cite journal|last1=Schulze|first1=Ulrik|last2=Ringel|first2=Michael|date=2013-06-01|title=What matters most in commercial success: first-in-class or best-in-class?|url=https://www.nature.com/articles/nrd4035|journal=Nature Reviews Drug Discovery|language=en|volume=12|issue=6|pages=419–420|doi=10.1038/nrd4035|pmid=23722339|s2cid=32258945|issn=1474-1784|url-access=subscription}} In fact, most blockbuster drugs (drugs with annual sales revenues exceeding {{US$|1000000000}}) were not first-in-class drugs. The economic potential of a first-in-class drug, which is typically priced higher than later drugs in the same class, has been largely declining due to efforts by health insurers to restrict what specialty drugs are covered and prevent incumbency advantages.{{Cite web|last=Longman|first=Roger|date=20 July 2015|title=The Shrinking Value of Best-in-Class and First-in-Class Drugs|url=https://invivo.pharmaintelligence.informa.com/IV004399/The-Shrinking-Value-Of-Best-In-Class-And-First-In-Class-Drugs|access-date=1 July 2021|website=In Vivo by Informa Pharma Intelligence}}

= Costs =

A lower number of available therapeutic options correlates with higher prices.{{Cite journal|last1=Kwa|first1=Michael C.|last2=Tegtmeyer|first2=Kyle|last3=Welty|first3=Leah J.|last4=Raney|first4=Sam G.|last5=Luke|first5=Markham C.|last6=Xu|first6=Shuai|last7=Kong|first7=Betty|date=2020-10-01|title=The relationship between the number of available therapeutic options and government payer (medicare part D) spending on topical drug products|url=https://doi.org/10.1007/s00403-020-02042-9|journal=Archives of Dermatological Research|language=en|volume=312|issue=8|pages=559–565|doi=10.1007/s00403-020-02042-9|pmid=32055932|s2cid=211111984|issn=1432-069X|url-access=subscription}} In addition, many first-in-class medications are specialty drugs and orphan drugs,{{Cite journal|last1=Chambers|first1=James D.|last2=Thorat|first2=Teja|last3=Wilkinson|first3=Colby L.|last4=Neumann|first4=Peter J.|date=2017-08-01|title=Drugs Cleared Through The FDA's Expedited Review Offer Greater Gains Than Drugs Approved By Conventional Process|journal=Health Affairs|volume=36|issue=8|pages=1408–1415|doi=10.1377/hlthaff.2016.1541|pmid=28784733|issn=0278-2715|doi-access=free}} which means that manufacturers have to recoup development costs from a smaller market.{{Cite journal|title=Balancing Lower U.S. Prescription Drug Prices And Innovation – Part 1 {{!}} Health Affairs Blog|url=https://www.healthaffairs.org/do/10.1377/forefront.20201123.804451/full/|journal=Health Affairs Forefront|year=2020 |language=en|doi=10.1377/forefront.20201123.804451 |last1=Lieberman |first1=Steven M. |last2=Ginsburg |first2=Paul B. |last3=Patel |first3=Kavita K. |url-access=subscription }} This raises ethical questions about the sustainability of the high prices on these costs.{{Cite web|last=Herper|first=Matthew|date=2019-12-23|title=The debate over America's drug-pricing system is built on myths|url=https://www.statnews.com/2019/12/23/debate-over-us-drug-pricing-system-time-to-face-reality/|access-date=2021-07-01|website=STAT|language=en-US}}{{Cite journal|last=Greene|first=Jan|date=January 2017|title=EpiPen Controversy Reveals Complexity Behind Drug Price Tags|url=https://www.annemergmed.com/article/S0196-0644(16)31329-4/fulltext|journal=Annals of Emergency Medicine|language=English|volume=69|issue=1|pages=A16–A19|doi=10.1016/j.annemergmed.2016.10.025|issn=0196-0644|doi-access=free|url-access=subscription}}

References