Biological medicines: antibodies and protein therapies

What is a biological medicine?

A biological medicine is a medicine whose active substance comes from a biological source – living cells or organisms such as human or animal cells, bacteria or yeast – rather than from chemical synthesis. Most biological medicines in current clinical use contain active substances made of proteins^[1].

Those proteins differ enormously in size and structural complexity. Insulin is a relatively simple protein of about 5,808 daltons; growth hormone is about 22,000 daltons; a monoclonal antibody is around 150,000 daltons^[1]. The larger and more folded the protein, the harder it is to produce consistently and the more it depends on a living production system.

Biological medicines offer treatment options for patients with chronic and often disabling conditions, including diabetes, autoimmune disease and cancers^[1]. They are typically given by injection or infusion rather than as a tablet, because a protein would be broken down in the digestive tract before it could reach its target.

One practical consequence follows from this biology: because biological medicines show natural variability and are more complex to manufacture, an exact replication of the molecular micro-heterogeneity is not possible. That is why a follow-on biological medicine is not regarded as a generic^[1].

How do monoclonal antibodies work?

An antibody is a Y-shaped protein found in the blood, also called an immunoglobulin. Antibodies are made by the immune system and released in response to a foreign substance, such as bacteria or viruses; they identify particular proteins (called antigens) on the surface of those substances and bind to them, which triggers the immune system to attack and destroy them^[2].

Scientists can make monoclonal antibodies in the laboratory. They are similar to the body's natural antibodies, and "monoclonal" means all one type – so each treatment is a large number of copies of a single antibody. Because a monoclonal antibody recognises one specific target, it can be directed at a defined protein or cell type. Monoclonal antibody treatments are a complicated group of drugs that work in different ways^[2].

• Blocking growth signals – many cancer cells carry large numbers of growth factor receptors on their surface; this type of antibody blocks the receptor so the cell no longer receives the signals it needs to survive. Pertuzumab is an example^[2].
• Carrying a payload – some antibodies have cancer drugs or radioactive substances attached; they are called conjugated monoclonal antibodies and deliver the drug or radioactive substance directly to the cancer cells. Trastuzumab emtansine is an example^[2].
• Blocking blood supply – some cancer cells make vascular endothelial growth factor (VEGF), which triggers blood vessel growth within the cancer; antibodies such as bevacizumab block VEGF from attaching to its receptors and are known as anti-angiogenic drugs^[2].
• Helping the immune system find cancer cells – some antibodies mark cancer cells so the immune system can find them more easily; rituximab attaches to a protein called CD20 found on some leukaemia and lymphoma cells^[2].
• Blocking the "hide" signal – antibodies called immune checkpoint inhibitors block the proteins that let cancer cells hide from the immune system^[2].
• Bringing cells together – a newer type called a T cell engager attaches to more than one target: one part binds a protein on T cells and another part binds the cancer cell, making it easier for T cells to destroy it^[2].

Some antibodies work by blocking a messenger rather than a cell surface receptor. In inflammatory conditions, dupilumab is a monoclonal antibody designed to block the receptors for interleukin 4 and interleukin 13 (IL-4 and IL-13), two proteins produced at high levels in patients with atopic dermatitis, some types of asthma, COPD, chronic rhinosinusitis with nasal polyposis, prurigo nodularis, eosinophilic oesophagitis and chronic spontaneous urticaria; blocking the receptors prevents IL-4 and IL-13 from working and relieves symptoms. Dupixent is given as an injection under the skin, usually in the thigh or belly, every week, every other week or every 4 weeks depending on the patient's age, weight and the condition being treated. Treatment must be started by a doctor experienced in diagnosing and treating the relevant conditions. Patients or carers may inject the medicine themselves if the doctor or nurse considers it appropriate and once they have been trained to do so^[3].

What are enzyme replacement and other protein therapies?

Not all biological medicines are antibodies. The broader category covers proteins of very different sizes and functions: from insulin and growth hormone to coagulation factors and monoclonal antibodies. Coagulation factors and other replacement proteins are the active substances in biological medicines approved in the EU that treat patients who are missing or produce too little of a specific protein^[1].

Because these medicines are proteins, they are given by injection or infusion. In psoriatic arthritis, biologic agents – immunosuppressant disease-modifying drugs made from biological proteins rather than artificial chemicals – are given by injection or infusion^[4].

How do biological medicines target inflammation in autoimmune disease?

Biologics used in psoriatic arthritis are designed specifically to block particular parts of the immune system that cause inflammation. This differs from conventional disease-modifying drugs such as methotrexate, which generally suppress the immune system, and from anti-inflammatories, which treat the symptoms of the disease^[4].

The mechanism is target-specific. The most commonly used biologic and biosimilar products block a messenger called TNF (tumour necrosis factor); alternatively they block the activation of certain immune cells (often T cells) or the release of other messengers, called interleukin 12/23 or interleukin 17, from those cells. The treatments act by copying the effects of substances naturally made by the immune system^[4].

Biologic and biosimilar agents usually work quickly to relieve the symptoms and swelling associated with psoriatic arthritis. Although studies show that most people improve within four to six weeks of treatment, a majority notice some improvement after the first or second injection or infusion – though some people can take the full 12 weeks to notice a response^[4].

How many antibody-based medicines are in development and use?

As of 1 May 2017, 74 antibody-based molecules had been approved by a regulatory authority in a major market. In addition, 70 antibody-based molecules were in phase III and 575 in phase I/II clinical trials^[5].

Those 719 antibody-based clinical-stage molecules include^[5]:

• 493 naked IgGs;
• 87 antibody-drug conjugates;
• 61 bispecific antibodies;
• 37 Fc fusion proteins in total;
• 17 radioimmunoglobulins;
• 13 antibody fragments;
• 11 immunocytokines.

In oncology, many of the new approaches involve antibody modulation of T cells. There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell-redirected bispecific antibodies and 145 chimeric antigen receptor (CAR) cell-based candidates, all currently in phase I or II clinical trials, totalling more than 250 T cell-interacting clinical-stage antibody-based candidates. Taken together, there were at least 864 antibody-based clinical-stage molecules or cells at that time^[5].

Some of these molecules are studied in publicly registered trials you can look up. One example is a phase II study combining pembrolizumab with oral metronomic cyclophosphamide in patients with chest wall breast cancer, registered under EudraCT number 2017-003343-37. Pembrolizumab is a selective, humanised anti-PD-1 monoclonal antibody that blocks interactions between PD-L1/PD-L2 and PD-1, which may reactivate immune surveillance and lead to improved anti-tumour activity^[6].

What do clinical trials of biological medicines look like for participants?

Trials of biological medicines are described by phase, and the phase tells you what the study is trying to answer. The table below summarises the development stage of antibody-based molecules as reported in the literature: approved products, phase III trials and phase I/II trials^[5].

Stage	What it covers	Example numbers reported	What it means for a participant
Approved for use	Molecules authorised by a regulatory authority in a major market	74 antibody-based molecules (as of 1 May 2017)[5]	The medicine has passed regulatory review and can be prescribed
Phase III	Later-stage clinical testing	70 antibody-based molecules[5]	You may be offered a treatment that is not yet authorised
Phase I/II	Earlier-stage clinical testing	575 antibody-based molecules[5]	You may be among the first people to receive the molecule

Within the phase I/II group, the categories of molecule differ in how they are built and what they do: naked IgGs (493), antibody-drug conjugates (87), bispecific antibodies (61), Fc fusion proteins (37), radioimmunoglobulins (17), antibody fragments (13) and immunocytokines (11)^[5].

If you are considering joining a trial, the registration number is the document that lets you check what the study is testing. The PERICLES study is registered under EudraCT number 2017-003343-37^[6]. Trials recruiting in Europe can also be searched on clinicaltrials.eu.

How are biological medicines monitored after they are authorised?

Once a biological medicine is on the market, information about its safety continues to be collected. A risk management plan (RMP) documents the safety concerns for a product and how they are monitored. For the adalimumab biosimilar Hulio, the RMP version 4.1, with a data lock point of 31 October 2025, sets out the summary of safety concerns and notes that post-marketing exposure data were updated to that data lock point^[7].

The RMP also records where information was aligned with the reference biologic Humira – for example, the missing information on "patients with immune-compromised conditions" and certain long-term safety topics in children was removed to align with the reference product's RMP, and the missing information on episodic treatment was updated to cover episodic treatment in ulcerative colitis^[7].

Specific populations can be under-represented in clinical trial programmes, and RMPs include a module on limitations in respect to populations typically under-represented in clinical trials, as well as exclusion criteria in pivotal studies^[7].

What should you report to your care team during treatment?

The most common side effects seen with injected medicines for psoriatic arthritis are skin reactions at the injection site. These occur in fewer than 30% of people and may last for up to two weeks^[4].

The most significant side effect of these medicines is an increase in the risk of all types of infections, including tuberculosis (TB). Before starting an anti-TNF medication, the risk of TB is assessed and a TB skin or blood test (Mantoux test) is often carried out. Treatment with these agents should be stopped while you have an active infection and are taking an antibiotic, or if you have a high fever^[4].

For some patients, a biological medicine is not appropriate. People with significant congestive heart failure should not take anti-TNF agents^[4].

What is a biosimilar and how is it approved in the EU?

A biosimilar is a biological medicine highly similar to another already approved biological medicine, called the reference medicine. Biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines, and the European Medicines Agency (EMA) is responsible for evaluating the majority of applications to market biosimilars in the European Union^[1].

Similarity is assessed in terms of structure, biological activity, efficacy, safety and immunogenicity profile – the intrinsic ability of proteins and other biological medicines to cause an immune response. The EU approved the first biosimilar in 2006^[1].

Evidence acquired over ten years of clinical experience shows that biosimilars approved through EMA can be used as safely and effectively in all their approved indications as other biological medicines^[1]. Both the originator form and the biosimilar version are approved according to the same standards of pharmaceutical quality, safety and efficacy^[4].

Patients and healthcare professionals have access to information materials developed by EMA and the European Commission to improve understanding of biosimilar medicines in the EU^[1].

What has been shown in studies of biological medicines?

For atopic dermatitis, Dupixent was more effective than placebo (a dummy treatment) at reducing the extent of disease. The medicine is authorised for moderate to severe atopic dermatitis in patients aged 12 years and over when topical treatments are not sufficient or appropriate, and can also be given to patients from 6 months to under 12 years of age if their condition is severe^[3].

For asthma, it is authorised in patients aged 6 years and over whose asthma is not properly controlled by appropriate combination therapy, and is added to maintenance treatment; it is only for patients with a type of airway inflammation called "type 2 inflammation"^[3].

The same medicine is also authorised for several other conditions, including chronic obstructive pulmonary disease in adults with increased levels of eosinophils, chronic rhinosinusitis with nasal polyposis in adults, moderate-to-severe prurigo nodularis in adults, eosinophilic oesophagitis in adults and children from 1 year of age weighing at least 15 kg, and moderate to severe chronic spontaneous urticaria in patients aged 2 years and over in whom antihistamines do not work well enough^[3].

Where does a report of a side effect go?

When a patient or healthcare professional reports a suspected side effect, it feeds into the safety monitoring of the medicine, and marketing-authorisation holders may gather further safety data once a product is available to patients^[4]. Your care team can tell you how to report.

When should you talk to your doctor or pharmacist?

Talk to your care team before stopping or pausing any biological medicine on your own. The RMP for adalimumab notes that long-term safety information has been collected in specific treatment situations and populations, and that some populations are typically under-represented in clinical trial programmes^[7].

Report promptly if you develop a high fever, signs of infection, or an injection-site reaction that spreads or persists beyond two weeks. Discuss any significant heart condition before starting an anti-TNF agent^[4].

If you are already injecting a medicine at home – as is possible with Dupixent after training – ask your doctor or nurse before changing the schedule or dose^[3].

This article is for information only and does not replace medical advice. Discuss any treatment decision with your doctor or pharmacist.

1. [1] Biosimilar medicines: Overview (accessed 02 June 2026) — https://www.ema.europa.eu/en/human-regulatory-overview/biosimilar-medicines-overview
2. [2] Monoclonal antibodies (mAbs) (accessed 02 June 2026) — https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/monoclonal-antibodies
3. [3] Dupixent (accessed 02 June 2026) — https://www.ema.europa.eu/en/medicines/human/EPAR/dupixent
4. [4] How do biologics work in psoriatic arthritis? (accessed 02 June 2026) — https://www.papaa.org/resources/learn-about-psoriasis-and-psoriatic-arthritis/just-diagnosed/what-is-psoriatic-arthritis/treatments-for-psoriatic-arthritis/biologics/
5. [5] Current progress in innovative engineered antibodies — protein-cell.net (accessed 06.10.2026) — http://protein-cell.net/article/doi/10.1007/s13238-017-0457-8
6. [6] ESMO Clinical Research Report – Combination of pembrolizumab with oral metronomic cyclophosphamide in patients with chest wall breast cancer (PERICLES): A phase II study (accessed 02 June 2026) — https://www.esmo.org/content/download/165403/3035878/1/ESMO-Clinical-Research-2018-Report-Bruno-Achutti-Duso.pdf
7. [7] Hulio EPAR – Risk Management Plan (accessed 02 June 2026) — https://www.ema.europa.eu/en/documents/rmp/hulio-epar-risk-management-plan_en.pdf