The term "me-too drug" or "follow-on drug" refers to a medication that is
similar to a
pre-existing drug, usually by making minor modifications to the prototype, reflected in slight changes in the profiles of
side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s or
activity, and used to treat conditions for which drugs already exist.
While pharmaceutical companies have justified the development of me-toos as offering incremental improvements in efficacy, side-effects, compliance and cost, critics have questioned the increasing
marketing
Marketing is the process of exploring, creating, and delivering value to meet the needs of a target market in terms of goods and services; potentially including selection of a target audience; selection of certain attributes or themes to emph ...
of me-toos, their absorption of
research and development
Research and development (R&D or R+D), known in Europe as research and technological development (RTD), is the set of innovative activities undertaken by corporations or governments in developing new services or products, and improving existi ...
resources and their impact on the innovation of new treatments.
In 1956,
Louis S. Goodman
Louis Sanford Goodman (August 27, 1906 – November 19, 2000) was an American pharmacologist. He is best known for his collaborations with Alfred Gilman, Sr., with whom he authored the popular textbook ''The Pharmacological Basis of Therapeutic ...
, co‐editor of ''
Goodman and Gilman'', referred to “the problem of the introduction of ‘me too’ drugs, that is, drugs without signal advantage of any sort”.
[ However, me-too drugs can be novel compounds themselves.] They are commonly used and include several beta blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
, antidepressants
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, heada ...
and stomach acid reducing and cholesterol lowering drugs.[
]
History
The term "me‐too drugs" was coined in the 1950s. In 1956, Louis S. Goodman
Louis Sanford Goodman (August 27, 1906 – November 19, 2000) was an American pharmacologist. He is best known for his collaborations with Alfred Gilman, Sr., with whom he authored the popular textbook ''The Pharmacological Basis of Therapeutic ...
, co‐editor of '' Goodman and Gilman'', referred to “the problem of the introduction of ‘me too’ drugs, that is, drugs without signal advantage of any sort”.[ Once a new drug class was discovered, other major drug companies made efforts to produce their own similar versions. Pharmacologist Milton Silverman and physician ]Philip R. Lee
Philip Randolph Lee (April 17, 1924 – October 27, 2020) was an American physician who served as the United States Assistant Secretary for Health, United States Assistant Secretary for Health and Scientific Affairs under President of the United ...
noted "the great drug therapy era was marked not only by the introduction of new drugs in great profusion and by the launching of large promotional campaigns but also by the introduction of what are known as 'duplicative' or 'me-too' products".
Between 1960 and 1962, Estes Kefauver
Carey Estes Kefauver (;
July 26, 1903 – August 10, 1963) was an American politician from Tennessee. A member of the Democratic Party, he served in the U.S. House of Representatives from 1939 to 1949 and in the Senate from 1949 until his d ...
, then Senator of Tennessee, led a series of hearings enquiring about the pharmaceutical industry's motive to produce me-too drugs after it was noted that much of their time and resources were spent producing them. Subsequently, the FDA required drug companies to prove their drugs were safe and effective.[ In 1964, ]Louis Lasagna
Louis Cesare Lasagna (February 22, 1923 – August 6, 2003) was an American physician and professor of medicine, known for his revision of the Hippocratic Oath.
Early life and education
Lasagna was an internationally recognized and respected e ...
described me-too drugs as being “hard to justify putting into man at all, let alone on the market”.[ Three years later, the term appeared in the '']Oxford English Dictionary
The ''Oxford English Dictionary'' (''OED'') is the first and foundational historical dictionary of the English language, published by Oxford University Press (OUP). It traces the historical development of the English language, providing a com ...
''.[ In the early 1970s, Silverman and Lee reported that there were almost 100 tranquillisers, 130 ]antihistamines
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
, greater than 270 antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
and more than 200 sulfonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
.[
In 1994, Desmond Laurence's textbook '']Clinical Pharmacology
Clinical pharmacology has been defined as "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinic ...
'' referred to me-too as "me-again".[
]
Definition
There is no agreed definition, however, several have been proposed,[ including:
*"multiple drugs within the same therapeutic class"
*"drugs that are chemically related to the prototype, or other chemical compounds which have an identical mechanism of action"
*"drugs which have more or less identical clinical outcomes to pre‐existing drugs"
*"a drug with a similar chemical structure or the same mechanism of action as a drug that is already marketed".][
]Biosimilar
A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved ...
s are compared with other biosimilars and are therefore not me-toos.
Examples
Me-too drugs include diazepam
Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, a ...
, ranitidine
Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. I ...
and esketamine
Esketamine, also known as (S)-ketamine or S(+)-ketamine, is the ''S''(+) enantiomer of ketamine, is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. It is sold under the brand ...
.[
]
Beta blockers
The first-in-class β-blocker pronethalol was developed by James Black at ICI Pharmaceuticals. It was followed by propranolol
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...
, sotalol
Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. It is only recommended in those with significant abnormal heart rhythms due to potentially serious side effects. Evidence ...
, practolol, metoprolol
Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. It is used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an a ...
, labetalol
Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less pref ...
, acebutolol
Acebutolol, sold under the brand names Sectral among others, is a beta blocker for the treatment of hypertension and arrhythmias. Acebutolol is a cardioselective beta-1 blocker and has intrinsic sympathetic activity. It is commonly used in the ...
and bisoprolol
Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is ...
. Successive differences between β-blockers have had a combined cumulative effect and are seen as "innovative".[
]
Benzodiazepines
15 benzodiazepines
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...
were marketed in the UK between 1960 and 1982, of which seven were produced by Roche.[
]
Proton pump inhibitors
The proton-pump inhibitor
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
They are the most potent inhibitors ...
Nexium
Esomeprazole, sold under the brand name Nexium among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Effectiveness is similar to o ...
by AstraZeneca
AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includin ...
is a me-too which was granted its patent by showing that it was effective for heartburn, not that it was better than its precursor, prilosec
Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome. It is also used to prevent upper g ...
. It was shown to preserve revenues of prilosec, whose U.S. patent expired in 2001. Considered a new drug by the FDA, nexium was patented separately, sold for eight times the cost of its generic
Generic or generics may refer to:
In business
* Generic term, a common name used for a range or class of similar things not protected by trademark
* Generic brand, a brand for a product that does not have an associated brand or trademark, other ...
esomeprazole
Esomeprazole, sold under the brand name Nexium among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Effectiveness is similar to ...
and advertised as significantly better than its predecessor, a move the company received much criticism for, with a subsequent class action lawsuit filed against them.
H2 antagonists
Both tagamet
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
The development of longer-acting H2 re ...
's and zantac's prices increased following the arrival of further me-too drugs pepcid and axid
Nizatidine is a histamine H2 antagonist, H2 receptor antagonist that inhibits gastric acid, stomach acid production, and is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease.
It was patented in 1980 and ...
.
ACE inhibitors
Several me-toos followed the prototype of the ace inhibitor
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...
, captopril
Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...
, with enalapril
Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosemide ...
being its first me-too.[ Most were as efficient as each other and had similar adverse effect profiles.]
Statins
When Merck's cholesterol-lowering statin Mevacor (lovastatin
Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat hypercholesterolemia, high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It ...
) was approved by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) in 1987, the understanding of the link between cholesterol and heart disease was improving, and the potential market for the drug became significant. Subsequently, several other companies developed similar drugs: Merck developed Zocor (simvastatin
Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart ...
) and Crestor (rosuvastatin
Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, ...
), Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
developed Lipitor (atorvastatin
Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.
Common ...
), Bristol-Myers Squibb
The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...
developed Pravachol (pravastatin
Pravastatin, sold under the brand name Pravachol among others, is a statin medication, used for preventing cardiovascular disease in those at high risk and treating abnormal lipids. It should be used together with diet changes, exercise, and w ...
), and Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
developed Lescol (fluvastatin
Fluvastatin is a member of the statin drug class, used to treat hypercholesterolemia and to prevent cardiovascular disease.
It was patented in 1982 and approved for medical use in 1994. It is on the World Health Organization's List of Essenti ...
). Others include pitavastatin
Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins.
Like other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis ...
(Livalo).[
]
Antidepressants
Imipramine
Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. The drug is also used to treat bedwetting. ...
was the first-in-class of the tricyclic antidepressants. Amitriptyline
Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...
, Nortriptyline
Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many a ...
, Dosulepin
Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the ...
and Doxepin
Doxepin is a medication falling in the tricyclic antidepressant (TCA) class used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For label updates seFDA index page for NDA 022036/ref> For hives it is a less pre ...
are some of the me-toos that followed.[
Several me-too ]Selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracell ...
have been developed for maintenance treatment in chronic depression. These include Paxil (paroxetine
Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...
), Celexa (citalopram
Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and socia ...
), Zoloft (sertraline
Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the differe ...
), Lexapro (escitalopram
Escitalopram, sold under the brand names Lexapro and Cipralex, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Escitalopram is mainly used to treat major depressive disorder and generalized anxiet ...
) and Prozac (fluoxetine
Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...
).
Debate
In 2005, a report by the International Policy Network
The International Policy Network (IPN) was a think tank based in the City of London, founded 1971, and closed in September 2011. It was a non-partisan, non-profit organization, but critics said it was a "corporate-funded campaigning group". IPN ...
defended me-toos, describing their development as "incremental improvements on already existing drugs". The report stated:
... this often represent(s) advances in safety and efficacy, along with providing new formulations and dosing options that significantly increase patient compliance. From an economic standpoint, expanding drug classes represent the possibility of lower drug prices as competition between manufacturers is increased. Additionally, pharmaceutical companies depend on incremental innovations to provide the revenue that will support the development of more risky “block-buster” drugs. Policies aimed at curbing incremental innovation will ultimately lead to a reduction in the overall quality of existing drug classes and may ultimately curb the creation of novel drugs.
This incremental innovation has led to some referring to me-toos as "me-betters".
Many physicians are unaware that me-toos are compared to placebos rather than pre-existing drugs. Me-toos are seen as patentable new drugs and therefore substantial profit makers, where innovative drugs may be more risky to develop.
Statistics
Between 1998 and 2003, the U.S. Food and Drug Administration (FDA) approved 487 drugs, of which 78 per cent appeared to have similar characteristics to pre-existing marketed drugs.
More than 60% of medicines listed on the World Health Organization's essential list are me‐too drugs.[
In September 2019, half of ]antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
under clinical development were “me-too” drugs. At the beginning of 2020, the WHO stated that only two of the 50 antibiotics in clinical development are active against serious drug resistant gram-negative bacteria, and most are not significant "upgrades" of drugs.
See also
* Unique selling point
In marketing, the unique selling proposition (USP), also called the unique selling point, or the unique value proposition (UVP) in the business model canvas, is the marketing strategy of informing customers about how one's own brand or product is ...
References
{{Reflist
Pharmaceutical industry
Drugs
Medical terminology